Vol. 02 NO 7
NEWS - PAGE 3
A DNA TEST THAT SCREENS NEWBORNS
FOR 193 GENETIC DISORDERS
BUDGET SPECIAL
FDA Approves First
Gram-Negative Antibiotic in over
15 years for Over Hospital-
Acquired Pneumonia
It is to include the treatment of hospital-ac-
quired bacterial pneumonia and ventila-
tor-associated bacterial pneumonia (HABP/
VABP) caused by the following susceptible
Gram-negative microorganisms: Klebsiella
pneumoniae, Enterobacter cloacae, Escheri-
chia coli, Serratia marcescens, Proteus mira-
bilis, Pseudomonas aeruginosa, and Haemo-
philus influenzae in patients 18 years of age
or older.
Hospital-acquired bacterial pneumonia
(HABP) and ventilator-associated bacterial
pneumonia (VABP) are serious bacterial in-
fections that occur in hospitalized patients,
which are associated with critically ill and
vulnerable populations. The economic bur-
den associated with HABP/VABP is signifi-
cant. These infections are associated with in-
creased healthcare costs, high morbidity and
GET THIS NEWSPAPER e-copy VIA WHATSAPP every week
NEWS - PAGE 4
INDIAN FARMS DOSING CHICKENS WITH
“LAST RESORT ANTIBIOTIC” IS
FOSTERING GLOBAL SUPERBUGS
mortality, and lengthened hospital stays.
The Dublin-based drugmaker said that this
expanded use is based on positive results
from a pivotal Phase 3 study evaluating the
efficacy and safety of AVYCAZ for the treat-
ment of adult patients with HABP/VABP.
In Trial 1, known as RECAPTURE, AVY-
CAZ was non-inferior to doripenem with
regard to both primary endpoints. In Trial 2,
known as REPRISE, AVYCAZ demonstrat-
ed a higher combined clinical and microbi-
ological cure rate vs. best available therapy
(BAT), including meropenem , imipenem ,
doripenem , and colistin . Additionally, both
trials included a subset of patients with infec-
tions caused by pathogens producing certain
ESBL groups and AmpC beta-lactamases in
which the clinical and microbiological cure
rates were similar to the overall results.
February 13th, 2018.
NEWS - PAGE 7 NEWS - PAGE 9
BACTERIUM PROTECTS PLANTS FROM SCIENTISTS DEVISE INTERACTIVE
DISEASE IN ATTEMPT TO GAIN MICROSCOPE, UNVEIL PHYSICAL
DOMINANCE PRINCIPLES OF CELL ORGANIZATION
NEW FDA APPROVAL |
First Gram-Negative
Antibiotic
Allergan plc’s supplemental New Drug
Application (sNDA) has now been ap-
proved by the USFDA to expand the ap-
proved use of Avycaz (ceftazidime and
avibactam).
By Disha Padmanabha
Certain types of Gram-negative bacteria Georgia/Augusta University, Augusta, GA.
have become increasingly resistant to avail-
able antibiotics, resulting in increased illness
and death as well as contributing to escalating
healthcare costs. New strategies to fight these
challenging infections have been long-await-
ed by the medical community.
David Nicholson, Chief Research and De-
velopment Officer, Allergan, said: “Health-
care providers in the U.S. have not had access
to a new treatment option for patients with
HABP/VABP due to Gram-negative bacteria
in over 15 years. Gram-negative pathogens
are some of the most pressing antibiotic re-
sistance threats and cause more than 40,000
resistant infections in the U.S. annually. To-
day’s action by the FDA is further evidence
of Allergan’s commitment to improving out-
comes and meeting critical needs in patients
with life-threatening infectious diseases.”
“Clinical efficacy along with patient safety
are critical priorities to clinicians managing
serious Gram-negative bacterial infections.
We are thrilled to have a new option avail-
able to treat HABP/VABP, some of the most
challenging Gram-negative infections in the
hospital setting,” said Jose Vazquez, M.D.,
FIDSA, Division Chief and Professor of Med-
icine Infectious Diseases, Medical College of
GIVE MISSED CALL TO
080-395-34707
1
February 13th, 2018.
RAINING VIRUSES? STUDY QUANTIFIES
MICROBES CIRCLING THE PLANET
Microbes are found even in the most mun-
dane of places, such as on our hands, in the
air and in soil. They grow and reproduce in
habitats where no other organisms can sur-
vive. They can be found in hot springs and
deep underground veins of water, in volcan-
ic rock beneath the ocean floor, in extreme-
ly salty water in the Great Salt Lake and the
Dead Sea, and below the ice of Antarctica.
Aerosolization of soil-dust and organic
aggregates in sea spray facilitates the long-
range transport of these bacteria, and likely
viruses across the free atmosphere. In one
such example, the team of researchers have
now, for the first time, quantified the virus-
es being swept up from the Earth’s surface
into the free troposphere, that layer of atmos-
phere beyond Earth’s weather systems but
below the stratosphere where jet airplanes
fly. The viruses can be carried thousands of
kilometres there before being deposited back
onto the Earth’s surface.
“Every day, more than 800 million virus-
es are deposited per square metre above the
planetary boundary layer—that’s 25 viruses
for each person in Canada,” said University
of British Columbia virologist Curtis Suttle,
one of the senior authors of the paper.
Their study, the first on the topic, found that
once the viruses are in the troposphere they
can travel thousands of kilometers before
falling back to earth. The troposphere is the
layer of the atmosphere past earth’s weath-
er systems yet below the stratosphere, which
is where jet planes travel. The phenomenon
might clarify why genetically similar viruses
are sometimes present in very completely dif-
ferent environments worldwide.
2
Vol. 02 NO 7
By Disha Padmanabha
“Roughly 20 years ago we began finding
genetically similar viruses occurring in very
different environments around the globe,”
says Suttle. “This preponderance of long-res-
idence viruses travelling the atmosphere
likely explains why—it’s quite conceivable to
have a virus swept up into the atmosphere on
one continent and deposited on another.”
The viruses and micro organism get carried
into the ambiance by hitching a trip on tiny
soil mud particles or sea spray. The team, in
order to determine how much of this material
is carried up above the atmospheric boundary
layer above 2,500 to 3,000 metres, travelled
to heights above 2,500 metres, the minimal
altitude at which particles are vulnerable to
being carried lengthy distances, in Spain’s
Sierra Nevada mountains and recorded
knowledge at numerous factors.
They found billions of viruses and tens of
millions of bacteria are being deposited per
square metre per day. The deposition rates for
viruses were nine to 461 times greater than
the rates for bacteria.
“Bacteria and viruses are typically deposit-
ed back to Earth via rain events and Saharan
dust intrusions. However, the rain was less
efficient removing viruses from the atmos-
phere,” said author and microbial ecologist
Isabel Reche from the University of Granada.
The researchers also found the majority of
the viruses carried signatures indicating they
had been swept up into the air from sea spray.
The viruses tend to hitch rides on smaller,
lighter, organic particles suspended in air and
gas, meaning they can stay aloft in the atmos-
phere longer.
Vol. 02 NO 7
A DNA Test That Screens
Newborns for 193 Genetic
Disorders
In the United States, newborns are typically
screened at the hospital for 34 health condi-
tions on the Recommended Uniform Screen-
ing Panel (RUSP), but the selected conditions
vary by state and represent only a fraction of
the genetic diseases that can manifest in a
child’s first decade of life. But now, a new-
ly launched DNA screening test has made it
possible to detect more than five times the
number of genetic diseases than a state’s
standard hospital test.
For all conditions covered by the test – in-
cluding atypical epilepsy, spinal muscular at-
rophy, and childhood cancers, among many
others – there are validated medical inter-
ventions that may positively influence a ba-
by’s future wellbeing when introduced early
enough.
The test uses saliva procured from a baby’s
cheek to screen for problematic genetic al-
terations, as well as potential reactions to a
range of medications usually given to young
children. All the conditions the Sema4 test
looks for—it uses DNA sequencing to exam-
ine a subset of genes, rather than the whole
genome—have some kind of treatment al-
ready available. The test also analyzes how
a baby is likely to respond to 38 medications
commonly prescribed in early childhood.
“If you can, at birth, canvass some of the
most common disorders, you get a better un-
derstanding of the health of your child,” says
Ants Could Help Us
Develop Novel, Potent
Antibiotics
You probably don’t think about them much.
They’re small and there’s probably a ton of
them in your front yard right now. But with
ants there is so much more than meets the
eye.
Now, in an addition to this list of all the
wondrous things about these little critters,
a new study has identified some ant species
that make use of powerful antimicrobial
agents – but found that 40 percent of ant spe-
cies tested didn’t appear to produce antibiot-
ics. The study has applications regarding the
search for new antibiotics that can be used in
humans.
“These findings suggest that ants could be a
future source of new antibiotics to help fight
human diseases,” says Clint Penick, an assis-
tant research professor at Arizona State Uni-
versity and former postdoctoral researcher at
North Carolina State University who is lead
author of the study.
“One species we looked at, the thief ant (So-
lenopsis molesta), had the most powerful an-
tibiotic effect of any species we tested – and
until now, no one had even shown that they
made use of antimicrobials,” says Adrian
Smith, co-author of the paper, an assistant re-
search professor of biological sciences at NC
State and head of the NC Museum of Natural
Sciences’ Evolutionary Biology & Behavior
February 13th, 2018.
Eric Schadt, the CEO of Sema4. “We think
parents want the best for their children and
are going to do whatever they can so that
their child can have the healthiest life pos-
sible.”
“Until now, families have been likely to be
caught off-guard by these early-onset diseas-
es, and prognosis is often poor by the time
symptoms have manifested. Thanks to break-
throughs in science and medicine, we can
now identify babies at risk for these broader
set of diseases and deliver interventions –
sometimes as simple as vitamin supplements
– in time to make a real difference. We be-
lieve Sema4 Natalis will give parents the ad-
vantage of early insight in support of the care
of their children.”
As noted in its recent comments to the
Centers for Medicare and Medicaid Services,
the National Organization for Rare Disorders
(NORD) finds that “on average, individuals
with a rare disease wait seven to 10 years to
obtain an accurate diagnosis, leaving many
individuals with chronic conditions still wait-
ing for a diagnosis. There are millions of pa-
tients in the U.S. who are still undiagnosed,
and [next-generation sequencing] may be
their only hope.”
By Disha Padmanabha
Research Lab.
Pathogens and parasites exert strong selec- By Disha Padmanabha
tive pressures on social animals due to the
which meant that an antimicrobial agent was search for species that actually do hold prom-
dense living conditions of social animals and
at work. For example, the slurry containing ise for biomedical research,” Smith says.
the high genetic relatedness among group
thief ant compounds showed no bacterial
members. In response, social species have
growth at all. “For example, the thief ant is closely relat-
evolved numerous strategies to combat path-
The team found that 12 of the 20 ant spe- ed to the red imported fire ant (Solenopsis
ogen spread.
cies had some sort of antimicrobial agent on invicta), which is well known for the antimi-
In addition to individual immune responses,
their exoskeletons – including some species, crobial properties of its venom. But in our
social species employ public health strate-
like the thief ant, that hadn’t previously been study, we found that the thief ant was even
gies to stop the spread of pathogens before
shown to do so. But eight of the ant species more effective against bacteria than the fire
they become prevalent. In social insects such
seemed not to make use of antibiotics at all. ant. There may be other species in the same
as ants, these strategies represent a form of
genus that are worth studying for their anti-
external immunity that includes grooming
“Finding a species that carries a powerful microbial potency.”
behaviours and the secretion of antimicrobial
antimicrobial agent is good news for those
compounds whose function is akin to our an-
interested in finding new antibiotic agents The researchers caution that this study is a
tibiotics. Because of the production of these
that can help humans,” Smith says. “But the first step, and that this study does have limita-
antimicrobial compounds, the identification
fact that so many ant species appear to have tions. For example, the researchers used only
of these social insects as promising sources
little or no chemical defense against microbi- one bacterial agent in their tests, meaning it is
of new and diverse antibiotics comes with
al pathogens is also important.” not clear how each species would fare against
little surprise.
other bacteria. “Next steps include testing ant
In the course of this study, researchers
“We thought every ant species would pro- species against other bacteria; determining
tested the antimicrobial properties associ-
duce at least some type of antimicrobial,” what substances are producing the antibiot-
ated with 20 ant species; using a solvent to
Penick says. “Instead, it seems like many ic effects – and whether ants produce them
remove all of the substances on the surface
species have found alternative ways to pre- or obtain them elsewhere; and exploring
of each ant’s body. The resulting solution
vent infection that do not rely on antimicrobi- what alternative strategies ants use to defend
was then introduced to a bacterial slurry. The
al chemicals.” against bacterial pathogens,” Smith says.
growth of the bacteria in the slurry was then
compared to the growth of bacteria in a con-
“The fact that not all ants use antimicrobi-
trol group. If bacteria in slurry that contained
als highlights the importance of refining our
ant solution grew less than the control group,
3
February 13th, 2018.
Trees Tolerate Extreme
Heatwaves by “Sweating”:
Study
Heatwaves are a regular climate component
in many areas of the world, consisting of
several consecutive days of extreme temper-
atures and a dry atmosphere, often combined
with dry surface soils.
Extreme heatwaves generally tend to have
devastating effects on the ecosystem. The re-
sponse of trees to extreme heatwaves is un-
certain but important for ecosystem function.
Some ecological processes are more sensitive
to changes in extremes than to changes in
mean values. For example, extreme tempera-
tures combined with prolonged drought have
been implicated as drivers of forest mortality.
High temperatures during extreme heat-
waves may exceed plant thermal thresholds,
leading to direct thermal damage or mortal-
ity unless plants can quickly adjust to these
extreme conditions. It is not clear, however,
whether rapid physiological adjustments in
thermal tolerance occur in response to heat-
waves in the field, or whether this is an effec-
tive protectant during the extreme heatwaves
that are predicted to occur in the future.
Now, researchers at the Western Sydney
University have uncovered the novel strate-
gies Australian eucalypt trees use to survive
extreme heatwaves. Of their findings, one re-
markable process involves the tree evaporat-
ing large volumes of water through its leaves
in a process similar to sweating.
In a year-long experiment, it was demon-
strated how trees continue to release water
through their leaves as an evaporative cool-
ing system during periods of extreme heat,
despite the carbon-fixing process of photo-
synthesis grinding to a halt.
The study lead, Prof Mark Tjoelker from
the University of Western Sydney’s Hawkes-
bury Institute for the Environment said the
findings had significant implications for cli-
mate change because they showed that trees
Indian Farms Dosing
Chickens with “Last
Resort Antibiotic” is
Fostering Global
Superbugs
In 1941, penicillin was first used to save
human life. But now, bacteria has emerged
resistant to every known antibiotic, and sci-
entists have begun to fear that the era of the
wonder drugs is near to its end.
And now in addition to this growing prob-
lem for which we can, frighteningly, do liter-
ally nothing about, we have been presented
with a new report that has found evidence of
considerable use of the antibiotic colistin, in
Indian poultry farms so as to promote growth
and feed efficiently.
For those who are ignorant enough to not
understand the gravity of this situation-
Colistin is considered the antibiotic of last
resort for use against Enterobacteriaceae, a
4
stopped capturing carbon during extreme
heatwaves, which are predicted to become
more frequent and severe in the future.
“If heatwaves occur over a large surface
area … clearly the trees and native forests
in that area would take up less carbon,” he
said. “And if there is an increased frequen-
cy of heatwaves that obviously impacts their
ability to serve as carbon sinks.”
The Earth has a mechanism in place to help
reduce the massive amount of carbon that hu-
mans have been emitting into the atmosphere
since the pre-industrial era. Oceans, grass-
lands and trees serve as “carbon sinks” that
sucks carbon from the atmosphere. Now, in
an ironic twist- the study suggests trees may
actually lose their ability to capture carbon
during heat waves.
The researchers, based within the Hawkes-
bury Institute for the Environment, used the
unique Whole Tree Chambers located at the
University’s Hawkesbury campus to im-
pose a year of warming and then a four-day,
high-intensity heatwave on trees local to the
Sydney region.
The Whole Tree Chambers are unique in
their ability to grow nearly full-height trees
(29.5 ft) in a fully controlled environment
and to be able to precisely and accurately
measure the trees’ rates of photosynthesis and
water use. Within the chambers, researchers
imposed an additional 3 degrees Celsius on
Parramatta Gums (Eucalyptus parramatten-
sis) to simulate the impacts of higher aver-
age temperatures in the Sydney region. After
12 months – in which time the trees grew to
more than 6 metres – researchers then im-
posed four days of heat at 43 degrees Celsius.
The observation was that the trees em-
ployed different strategies in order to cope
family of bacteria that contain organisms that
we interact with every day; many of which
have become superbugs.
But then, in India, this weapon of last re-
sort is being fed to birds to make them gain
weight faster so more can be grown each year
at greater profit. When the antibiotic should
be used as a last resort to save human lives, it
is instead (tons of it) is being used on chick-
ens. And what happens is our antibiotic of
last resort will be decoded by the bacteria
encountered in the animals, and then inacti-
vated.
The World Health Organisation has called
for the use of such antibiotics, which it calls
“critically important to human medicine”, to
These chambers allow researchers a better understanding of how plants adjust to altered climate conditions
(Credit: Western Sydney University – Hawkesbury Institute for the Environment)
with the heat, rather to avoid the damaged
due to the heat.
The trees stopped their leaves from reach-
ing critically high temperatures by evapo-
rating large quantities of water, in a process
called transpiration that is akin to sweating.
Under dry conditions, plants would normally
stop transpiring in order to conserve water. In
heatwaves, in contrast, trees must keep using
water to avoid leaf damage from burning.
To maintain the high rates of transpiration,
the trees sourced water from throughout the
soil profile, to depths of 1.5 metres and be-
low, demonstrating the efficiency with which
eucalypts find and extract water.
Further, the trees even rapidly increased
their high-temperature tolerance. Within 24
hours of the start of the heatwave, the thresh-
old temperature at which leaves start to be-
come damaged had increased by 2 degrees
Celsius.
“What normally happens is that a tree’s use
of water and its rate of photosynthesis are
closely related and this process is the basis
of how scientists predict what the effects of
a warmer Australia on trees and forests will
be,” explains Professor Mark Tjoelker.
be restricted in animals and banned as growth
promoters. Their continued use in farming in-
creases the chance bacteria will develop re-
sistance to them, leaving them useless when
treating patients.
A report by the Bureau of Investigative
Journalism found 2,800 tonnes of the drug
were shipped to developing countries includ-
ing India, Vietnam, Russia, Mexico, Colom-
bia and Bolivia for use on animals in 2016.
India, which is regarded as one of the worst
offenders for antibiotic misuse, received hun-
dreds of tonnes of colistin for routine use in
animals, particularly chickens.
The south Asian nation is expected to see
the highest growth in drug use in animals of
Vol. 02 NO 7
By Disha Padmanabha
“Under these extreme temperatures, this re-
lationship changes completely – the trees can
no longer photosynthesise, but they continue
to use a lot of water to keep their leaves from
reaching damagingly high temperatures. In
addition, the ability to increase the high-tem-
perature tolerance of their leaves helps to ex-
plain how eucalypts cope with heatwaves that
would burn the leaves of other species.”
Dr John Drake, formerly of the Hawkes-
bury Institute for the Environment and now
a researcher at the College of Environmental
Science and Forestry in the United States, ex-
plains that there is a limit to all plants’ ability
to adjust to heat even if some species adapt
better than others.
“We were surprised how well these euca-
lypts acclimated to the heatwaves and main-
tained their function,” says Dr Drake.
“This indicates that eucalypts can tolerate
elevated temperatures and significant heat-
wave events as long as they have access to
water. If heat and drought combine, then we
may see more damage occurring and the po-
tential for tree mortality”, he says.
By Disha Padmanabha
any country over the next decade, with esti-
mates suggesting as much as 4,800 tonnes of
antibiotics will be used in feed by 2030 – an
80 per cent increase on current levels.
Although, the World Health Organisation
calls this drug “critically important to human
medicine”, it also restricts its use in animals
and bans it as a growth promoter. In India
itself, there are at least five pharmaceutical
companies that openly advertise products
with Colistin as growth promoter.
Next Page>>>>
Vol. 02 NO 7
One of these companies, Venky’s, is also a
major poultry producer. Apart from selling
animal medicines and creating its own chick-
en meals, it also supplies meat directly and
indirectly to fast food chains in India such as
KFC, McDonald’s, Pizza Hut and Dominos.
The study quotes Professor Timothy Walsh,
an adviser to the UN on antimicrobial re-
sistance, who says, “Colistin should only be
used on very sick patients. Under any other
circumstances it should be thought of and
Scientists Design Novel
Technology Platform to
Reboot Bacteriophages
The unique host specificity and antimicro-
bial activity of bacterial viruses have inspired
many diagnostic and antibacterial applica-
tions in industry, agriculture, and medicine.
Because of the rise in antibiotic-resistant in-
fections, phage therapy is a reemerging field
of interest.
Specially, the engineered strains of bacteri-
ophages provide powerful tools for biotech-
nology, diagnostics, pathogen control, and
therapy. However, current techniques for
phage editing are experimentally challenging
and limited to few phages and host organ-
isms.
In this direction, scientists at ETH Zu-
rich, led by Martin Loessner, Professor of
Food Microbiology, have now developed
a technology platform that allows them to
systematically modify and customise bacte-
riophages. The platform technology enables
rapid, accurate, and selection-free construc-
tion of synthetic, tailor-made phages that in-
fect Gram-positive bacteria.
The new phage workbench allows such
viruses to be created very quickly and the
Bacteria ‘Fight Club’:
Guardians of the Gut
Fight it Out
Fight! Fight! Fight!
A tale of survival in the Microbial Jungle
proceeds.
There’s a war going on that you’re com-
pletely oblivious to, even though it’s all hap-
pening right under your nose- well, actually
inside of you. Rival Strains of Escherichia
coli compete for precious real estate within
the damp linings of your gut.
You cannot really ever guess how much
bacteria like a good fight until you’ve seen
this video, scientists at the University of Ox-
ford have made. They literally stab, shove
and poison each other in pursuit of the best
territory.
For the first time, scientists have observed
in real-time the ability of bacteria within a
colony to collectively predict and respond to
an incoming attack by another colony. This
discovery has important implications for un-
derstanding both the healthy bacteria that live
in the human body and the bacteria responsi-
ble for spreading disease.
Animals have evolved a wide diversity of
aggressive behavior often based upon the
careful monitoring of other individuals. Bac-
treated as an environmental toxin. It should
be labelled as such. It should not be export-
ed all over the world to be used in chicken
feed.”
Professor Walsh, who is professor of med-
ical microbiology at Cardiff University, dis-
covered a colistin-resistant gene in Chinese
pigs in 2015. The gene, mcr-1, could be
transferred within and between species of
bacteria. That meant that microbes did not
have to develop resistance themselves – they
“toolbox” is extremely modular: it allows the
scientists to create almost any bacteriophages
for different purposes, with a great variety of
functions.
“Previously it was almost impossible to
modify the genome of a bacteriophage,”
Loessner says. On top of that, the methods
were very inefficient. For example, a gene
was only integrated into an existing genome
in a tiny fraction of the phages. Isolating
the modified phage was therefore often like
searching for a needle in a haystack.
“In the past we had to screen millions of
phages and select those with the desired
characteristics. Now we are able to create
these viruses from scratch, test them within
a reasonable period and if necessary modify
them again,” Loessner stresses.
In the course of the study, the team used syn-
thetic biology methods to plan the genome of
a bacteriophage on the drawing board and as-
semble it in a test tube from DNA fragments.
teria are also capable of aggression, with
many species using toxins to kill or inhibit
their competitors. Like animals, bacteria also
have systems to monitor others during an-
tagonistic encounters, but how this translates
into behavior remains poorly understood.
However, now the researchers have ob-
served such behaviour through warring mi-
crobes. They used two strains of Escherichia
coli, pitting them against each other. Both
strains were engineered to have either flu-
orescent green or red colors so the Oxford
scientists could “follow their combat in real
time.” They saw that each strain produced
their own toxin as a weapon against the other
strain, but the bacteria were not negatively
affected by their own toxin.
The findings revealed that not all strains
of bacteria fight the same way. In addition
to these basic differences in aggression, the
research also shows that some strains can not
only detect an attack from an incoming toxin,
but they can also respond quickly to warn the
rest of the colony.
Cells on the edge of the colony will detect
the incoming attack, and share this infor-
could become resistant just by acquiring the
mcr-1 gene.
“Colistin-resistant bacteria will spread on
the chicken farms, in the air surrounding
them, contaminate the meat, spread to the
farm workers, and through their faeces flies
will spread it over large distances,” Prof
Walsh further added.
Probably, a bigger issue here is- there is
nothing to prevent Indian farmers, which in-
At the same time new, additional functions
were incorporated in the phage genome, such
as enzymes to dissolve the bacterial cell wall.
They were additionally able to remove
genes that give a phage unwanted properties,
such as the integration into the bacterial ge-
nome or the production of cytotoxins.
In order to reactivate a phage from syn-
thetic DNA, the genome was introduced into
spherical, cell wall-deficient but viable forms
of the Listeria bacterium (L-form Listeria).
Based on the genetic blueprint, these bacte-
rial cells then produce all the components of
the desired phage and ensure that the virus
particles are assembled correctly.
mation with the cells behind the battlefront,
allowing them to respond as a collective, in
a coordinated and surprisingly sophisticated
fashion.
Professor Kevin Foster, senior author on
the work and Professor of Evolutionary Bi-
ology in the Department of Zoology at the
University of Oxford, said: “Our research
shows that what appear to be simple organ-
isms can function in a very sophisticated
manner. Their behaviour is more complex
than we have previously given them credit for.
Much like social insects, such as honey bees
and wasps and social animals like birds and
mammals who use alarm calls, when under
predation, they are capable of generating a
coordinated attack.”
Given how the human body is home to vast
February 13th, 2018.
clude some of the world’s biggest food pro-
ducers, from exporting their chickens and
other related products overseas.
The finding is alarming given the use of
such powerful drugs can lead to an increas-
ing resistance among farm animals around
the world. Colistin, being regarded one of the
last lines of defence against serious diseases
could lead to breakouts and diseases com-
monly treatable previously, becoming deadly
once again in its absence.
By Disha Padmanabha
The team, with this project, has undoubted-
ly made a giant stride towards applying syn-
thetic bacteriophages for use in therapy, di-
agnostics or the food industry. The scientists
are thus managing to overcome constraints
associated with the use of naturally occur-
ring phages. “Our toolbox could help to ex-
ploit the potential of phages,” Loessner says.
The researchers have applied for a patent
for their technology. They next hope to find
licensees to produce the phages for therapy
and diagnostics.
By Disha Padmanabha
numbers of bacteria, particularly our gut mi-
crobiome, this effectively means that there is
a bacterial war going on inside us. Under-
standing bacterial competition can help us to
understand how bacteria spread, where and
why. Professor Foster explains: “We know
from other studies that toxins are important
for whether or not a particular strain will
establish in a community. But understanding
how bacteria release toxins and outcompete
others is very important for understanding
the spread of infection.”
Witness the two epic colonies
(of bacteria) engaging in battle,
Game of Thrones style, here:
https://youtu.be/pg6WUDn16Us
5
February 13th, 2018.
Artificial
Superconducting
Synapses Could Enable
More Efficient- And More
Human AI Systems
For those working in the field of advanced
artificial intelligence, getting a computer to
simulate brain activity is a gargantuan task,
but it may be easier to manage if the hard-
ware is designed more like brain hardware to
start with.
Artificial intelligence software has increas-
ingly begun to imitate the brain. Algorithms
such as Google’s automatic image-classifi-
cation and language-learning programs use
networks of artificial neurons to perform
complex tasks. But because conventional
computer hardware was not designed to run
brain-like algorithms, these machine-learn-
ing tasks require orders of magnitude more
computing power than the human brain does.
And now researchers at the National Insti-
tute of Standards and Technology may have
overcome this significant hurdle by design-
ing a chip with artificial synapses.
The researchers have built a superconduct-
ing switch that “learns” like a biological sys-
tem and could connect processors and store
memories in future computers operating like
the human brain.
In the brain, neurons “talk” to one another
Compromised
“Gatekeeper” Cells Could
be Precursors of
Alzheimer’s
A new potential for alzheimer’s has been
identified by researchers- the protective
“gatekeeper” cells of tiny blood vessels.
Normally, the blood vessels in the brain
form a tight barrier, preventing toxins and
large molecules from flooding the brain,
while allowing oxygen and nutrients in. But
as people age, the researchers found, this
blood-brain barrier starts to break down. The
process was found to accelerate in those in
the earliest stages of Alzheimer’s disease.
“This is a significant step in understanding
how the vascular system affects the health
of our brains,” said the senior author of the
study, Dr. Berislav Zlokovic, director of the
Zilkha Neurogenetic Institute at USC. “To
prevent dementias, including Alzheimer’s,
we may need to come up with ways to reseal
the blood-brain barrier and prevent the brain
from being flooded with toxic chemicals in
the blood.”
The catastrophe causes a communications
failure called small vessel disease. Many
people with that disease also have white mat-
ter disease, the wearing away of fatty mye-
lin that allows neurons to transfer messages
6
by sending electrochemical impulses across
tiny gates or switches called synapses. When
a synapse receives a strong enough incoming
signal from one neuron, it triggers an electro-
chemical reaction that produces an outgoing
spike in a second neuron.
“The NIST synapse has lower energy needs
than the human synapse, and we don’t know
of any other artificial synapse that uses less
energy,” NIST physicist Mike Schneider said
in a statement.
Even better than the real thing, the NIST
synapse can fire much faster than the human
brain—1 billion times per second, compared
to a brain cell’s 50 times per second—using
just a whiff of energy, about one ten-thou-
sandth as much as a human synapse.
The NIST synapse is a type of Josephson
Junction, a sandwich of two superconductors
around an insulating layer. What makes this
unique is the fact that these synapses special
is that the insulating layer is packed with spe-
cial magnetic clusters that allow the research-
ers to control how much energy is required
within the brain network.
“Many scientists have focused their
Alzheimer’s disease research on the buildup
of toxic amyloid and tau proteins in the brain,
but this study and others from my lab show
that the problem starts earlier — with leaky
blood vessels in the brain,” said Berislav
Zlokovic.
“The collapse of pericytes — gatekeeper
cells that surround the brain’s smallest blood
vessels — reduces myelin and white matter
structure in the brain. Vascular dysfunctions,
including blood flow reduction and blood-
brain barrier breakdown, kick off white mat-
ter disease.”
The brain has a dense network of blood
vessels, which if stretched end-to-end would
cover more than 5,000 football pitches. How-
ever, unlike the blood vessels in other parts of
the body, these vessels restrict which things
can enter the brain from the blood stream. It
does that by forming a physical overlap of
cells, such as pericytes and endothelial cells,
that make up the blood vessel wall and forms
tight junctions that control the entry and re-
to throw the switch, known as the critical
current.
As Schnieder noted, these junctions include
20,000 manganese and silicon nanoclusters
per square micrometer. They gave the re-
searchers the control they needed.
“These are customized Josephson junc-
tions,” he noted. “We can control the number
of nanoclusters pointing in the same direc-
tion, which affects the superconducting prop-
erties of the junction.”
Ultimately, these synapses could play crit-
ical roles in making processing data simul-
taneously a reality. Neuromorphic computers
could be the new wave of reality given the
increasing need for faster computing at lower
energy costs.
Moreover, the team adds, the synapses can
Diffusion MRI maps show disrupted white matter connectivity and loss of white matter
fiber tracts in 1 year-old pericyte-deficient mice. (Image/Berislav Zlokovic Lab)
moval of substances into and out of the brain.
Pericytes play a critical role in white matter
health and disease via fibrinogen, a protein
that circulates in blood. Fibrinogen develops
blood clots so wounds can heal. When gate-
keeper cells are compromised, an unhealthy
amount of fibrinogen slinks into the brain
and causes white matter and brain structures,
including axons (nerve fibers) and oligoden-
drocytes (cells that produces myelin), to die.
Therefore, the team of researchers at the
USC proceeded to bioengineer mice to have
25 percent fewer of pericytes. They then
prodded the hind legs of the young specimens
with an electric stimulus.
The pericyte-lacking mice showed an ap-
proximately 30 percent reduction in blood
flow in the brain versus normal mice, be-
cause their capillaries took about 6.5 seconds
longer to open up in the face of the stimulus.
Further, as the specimens aged, it was ob-
Vol. 02 NO 7
By Disha Padmanabha
be ‘stacked’ in a three-dimensional arrange-
ment to form a larger system linking devices
acting as neurons, which the term says can be
made by conventional electronic component
construction methodology.
Steven Furber, a computer engineer at Uni-
versity of Manchester, UK, who studies neu-
romorphic computing, stresses that practical
applications are far in the future. “The device
technologies are potentially very interesting,
but we don’t yet understand enough about the
key properties of the [biological] synapse to
know how to use them effectively,” he says.
“We’re optimistic that we can start to scale
these devices somewhat aggressively,” said
Schneider, who puts the figure at between five
and 10 years.
By Disha Padmanabha
served that the cerebral blood-flow response
got even worse, dipping to 58 percent lower
than their unaffected brethren at six to eight
months of age.
“We now understand the function of blood
vessel gatekeeper cells is to ensure adequate
oxygen and energy supply to brain cells,”
said Amy Nelson, co-first author and a post-
doctoral scholar at the Zilkha Neurogenetic
Institute. “Prior to our study, scientists knew
patients with Alzheimer’s disease, ALS and
other neurodegenerative disorders experi-
ence changes to the blood flow and oxygen
being supplied to the brain and that pericytes
die. Our study adds a new piece of informa-
tion: Loss of these gatekeeper cells leads to
impaired blood flow and insufficient oxygen
delivery to the brain. The big mystery now is:
What kills pericytes in Alzheimer’s disease?“
Vol. 02 NO 7 February 13th, 2018.

New Form of Botox

Isolated from Bacterial
Source
Clostridium botulinum toxin which can
cause a severe flaccid paralytic disease in
human and other animals, had the ability to
jump into gram-positive bacteria called En-
terococcus faecium, through plasmids in
the bacteria, a tiny, double-stranded circular
DNA molecule that is distinct from a cell’s
chromosomal DNA, according to a new
study.
Over the past 20 years, there has also been
a growing number of therapeutic applications
for botulinum toxin type A, known as Bot-
ox, including treatment for migraines, leaky
bladders, excessive sweating, and cardiac
conditions.
“This is the first time that an active botu-
linum toxin has been identified outside of
Clostridium botulinum and its relatives,
which are often found in soil and untreated
water,” said Andrew Doxey, one of the study’s
two corresponding authors and a bioinfor-
matics professor at the University of Water-
loo. “Its discovery has implications in sev-
eral fields, from monitoring the emergence
of new pathogens to the development of new
protein therapeutics—it’s a game changer.”
The study was originally designed to inves-
tigate the origins of antibiotic resistance in E.
faecium bacteria, later, the researchers were
able to sequence the genome of the E. faeci-
um bacteria drawn from cow feces.
The genome was then run through com-
puter programs in Doxey’s lab, which found
the gene for botulinum toxin in the bacterial
By Disha Padmanabha
strain.
The researchers concluded that the botuli- different species. the Doxey Lab and one of the study’s lead au-
num toxin was likely transferred from C. bot- thors. “By finding more versions of the tox-
ulinum bacteria in the environment into the “The botulinum toxin is a powerful and in in nature, we can potentially expand and
E. faecium bacteria in the cow’s gut, showing versatile protein therapeutic” says Michael optimize its therapeutic applications even
that the toxin can be transferred between very Mansfield, a Biology doctoral candidate in further.”

Bacterium Protects Plants

from Disease in Attempt to
Gain Dominance
Most natural environments harbor a stun-
ningly diverse collection of microbial spe-
cies. Within these communities, bacteria
compete with their neighbors for space and
resources.
Members of the rare biosphere that are am-
plified under favorable conditions to which
they are pre-adapted can give rise to discrete,
abundant populations. The potential pool of
microbial competitors is therefore vast, and a
wide range of mechanisms can be responsible
for the emergence and radiation of dominant
microbial populations. Nutritional resources
are a focal point of microbial competition.
Now, in this regard, another warring bacte-
rium has been found by the scientists at Mc-
Master University. They have also been able
to identify a toxin the soil-dwelling bacteri-
um employs to get rid of its enemies which in
turn has been found to offer protection to the
plant against its pathogens.
The bacterium Pseudomonas protegens hold
the ability to kill soil-dwelling plant patho-
gens, including fungi and bacteria that attack
the roots of important crops such as cotton by
the means of the toxic, T6SS injection.
“[The T6SS] is this molecular nanomachine
that injects toxic protein into other species of
bacteria and kills them,” lead researcher,
John Whitney said. “Plant protective bacte-
ria that have [T6SS] can protect plants from
pathogens better relative to [bacteria] that
don’t have it.”
Pseudomonas protegens releases diverse
antimicrobial compounds into the soil, but
the study focused specifically on those com-
pounds that it was injecting directly into
other bacteria through the type VI secretion
system, or T6SS.
Understanding the diversity of bacterial
weapons is an active area of study among
agricultural researchers who would like to
develop better ways to fight plant diseases.
Through the course of the study, the team
found that the toxic protein used by P. pro-
tegens against other bacteria acts on a mol-
ecule found in nearly all living cells: nico-
tinamide adenine dinucleotide, or NAD+. It
is a cofactor, or “helper” molecule, in many
biochemical reactions. By injecting a protein
that destroys NAD+, P. protegens is able to
kill other bacteria.
Delving deeper, the team next analysed
the genome of several other bacteria to de-
termine how widespread the strategy of tar-
geting NAD+ is in microbial warfare. They
found that many bacteria with secretion sys-
tems carry genes similar to the one encoding
the NAD-targeting toxin.
“We started to see that this isn’t just a way
By Disha Padmanabha
of killing that is enacted by plant-protective
bacteria,” Whitney said. “If you look at the
distribution of this (protein) among all se-
quenced bacteria, it appears that many differ-
ent bacteria in many different environmental
niches use this mode of action to outcompete
other bacteria.”
“The identification and characterization of
antibacterial toxins produced by plant-pro-
tective bacteria may one day allow us to en-
gineer these bacteria to have enhanced abili-
ty to suppress pathogens,” Whitney said.

7
February 13th, 2018. Vol. 02 NO 7

Dye Wipes Out Malaria

Parasite at Unprecedented
Rate
The malarial parasite along with its now re-
sistant form has rendered our best weapons
against it moot and our medications on the
brink of defeat.
The World Health Organization (WHO)
estimated 800,000 malaria deaths and 225
million cases worldwide in 2010. Accord-
ing WHO, malaria is chargeable for roughly
445,000 deaths once a year. Geographically,
malaria overlaps with other infectious mal-
adies including HIV, which often compli-
cate the illness as well as treatment options.
Worryingly, first-line treatment for malaria
currently relies on a single drug class called
artemisinins, and the existing drug armamen-
tarium is insufficient to answer the call for
malaria eradication.
Under the circumstances, scientists are ex-
ploring many approaches, targeting different
stages of the parasite life cycle, to find agents
that will prevent, cure, or eliminate malaria.
But now, a new research has found that the
dye methylene blue is a safe antimalarial that
kills malaria parasites at an unparalleled rate.
Methylene blue has had a fascinating ca-
reer. Its history goes back to the 19th centu-
ry, when it was the first synthetic dyestuff on
the market and began to put pressure on its
predecessors, plant-based dyes. Now, in the
study carried out by scientists at Radboud
University Medical Center, the University of
California (UCSF), and the Malaria Research
and Training Center (MRTC), at Mali, they
were able to ascertain the fact that the dye
in combination with artemisinin-based com-
bination therapy (a fairly standard treatment)
was able to get rid of malaria in a short period
of time.
“Methylene blue is very promising, because
it can prevent the spread of malaria within
such a short time following treatment,” said
Teun Bousema, researcher from Radboud
University in the Netherlands.
“There are also indications that methylene
blue also works well in species that are resist-
ant to certain medicines,” Bousema added.
As the malaria parasites remain in the blood
for a long time, with the chance that other
mosquitos are infected if they feed on the
patient, our current medications are pretty
useless. The parasites split in the patient’s By Disha Padmanabha
red blood cells, forming male and female
sex cells (gametocytes). If another mosquito Researcher Teun Bousema (Radboudumc) humans. Bousema: “Methylene blue is very
bites the patient, it sucks up the sex cells and coordinated the study which was conducted promising, because it can prevent the spread
these are fertilized in the mosquito’s stom- together with the University of California of malaria within such a short time follow-
ach. The offspring then find their way to the (UCSF) and the Malaria Research and Train- ing treatment. There are also indications that
mosquito’s salivary glands, where the cycle ing Center (MRTC). Bousema: “We noted methylene blue also works well in species
starts again. that the male parasites disappeared from the that are resistant to certain medicines.” The
bloodstream more quickly than the female dye is safe and was tolerated well by patients.
In the new study, adding the dye to the an- parasites.” There is however just one awkward side ef-
timalaria medicine ensured that patients no fect: “I have used it myself, and it turns your
longer infected other mosquitos, within as Encouraged by the promising results of lab- urine bright blue. This is something that we
little as 48 hours. Patients who were not giv- oratory experiments, Bousema’s team has in- need to solve, because it could stop people
en methylene blue were able to infect other vestigated for the first time the effect of meth- from using it.”
mosquitos for at least a week. ylene blue on the spread of malaria amongst

Active Genetics Paves Way

for a New Era of Advances
in Synthetic Biology
We are all very well aware of Mendelism.
Though he was not aware of the concept of
genes at the time was his experiments, Men-
del essentially worked out that pea plants had
two copies of each gene, and that each copy
had a 50% chance of being passed on to any
one offspring. Yet not all genes actually fol-
low this pattern of inheritance.
The non-Mendelian transmission of herita-
ble traits or known as Active Genetics, takes
place by means of self-propagating genetic
elements. It was first conceived and devel-
oped at UC San Diego in pioneering work on
the fruit fly, Drosophila melanogaster (Gantz
and Bier, 2015).
It is an exciting new technology that can
also be used to bypass prohibitive constraints
imposed by standard genetic methods to per-
mit aggregation of multiple naturally occur-
ring genetic variations in crop strains. It has
immense potential in transforming health and
agriculture.
Immediate targets of active genetics includ-
ed gene-drive systems for immunizing mos-
quitoes against vector borne diseases such as
malaria. Bier and Gantz also proposed using
active genetics for a variety of other potential
human health and agricultural benefits.
A research team now, led by Shannon Xu,
together with Gantz and Bier, has employed
CRISPR/Cas9 in order to edit gene regula-
tory elements in their native genomic envi-
ronments, revealing new fundamental mech-
anisms that control gene activity. Their work
also provides experimental validation for
using active genetics as an efficient means
for targeted gene insertion, or “transgenesis,”
and single-step replacement of genetic con-
trol elements.
To understand mechanisms controlling
gene activity in space and time, the research-
ers analyzed the genetic control of a gene re-
sponsible for coordinating the formation of a
simple structure in fruit flies—a wing vein—
during its development.
The team used a new active genetic element
called a CopyCat element and more tradi-
tional genome editing to analyze the control
of a gene that coordinates the formation of a
simple structure in a fruit fly – a vein in the
wing. So-called “CopyCat” cloning vectors
offer the potential to be inserted precisely
into the genome at any desired location and
then get copied with high efficiency from one
parental chromosome to another so that all
offspring inherit the CopyCat element.
As a result, the researchers found evidence
for a new potential form of interaction be-
tween chromosomes that contributes to the
control of gene activity. These observations
UC San Diego Professor Ethan Bier. Credit: Erik Jepsen, UC San Diego Publications
raise the intriguing possibility that similar
forms of cross-talk between chromosomes
may occur in other organisms and might
eventually define potential targets for epige-
netic intervention.
Additionally, their work demonstrates sig-
nificant advantages of editing gene regulatory
sequences in their native location to uncover
new functionalities. This leads to a better un-
derstanding of how control switches work to
turn genes on and off in the body. Perhaps
most importantly, these studies demonstrate
the general utility of active genetics as a plat-
form for engineering new organisms with
novel traits.
“These advances should encourage other
researchers to employ active genetics in a
broad range of organisms to enable and ac-
celerate their research,” said Xu.
By Disha Padmanabha
“This knowledge may eventually lead to
biological design based on first principles.
That is, acquiring the knowledge to engineer
organisms with specifically designed novel
features,” said Bier, professor and recently
named holder of the Tata Chancellor’s En-
dowed Professorship in Cell and Develop-
mental Biology.
“Such genetic engineering manipulations
should open new avenues of research and
animal and plant engineering that are out
of reach using current technologies,” the
researchers note. These innovative new are-
as of biological research are in line with the
goals of the Paul G. Allen Frontiers Group,
which named professor Bier an Allen Distin-
guished Investigators in 2016.

8
Vol. 02 NO 7
Algae Underside of
Arctic Thrive Even at
0.02% Light
Microalgae colonizing the underside of
sea ice in spring are a key component of the
Arctic foodweb as they drive early primary
production and transport of carbon from the
atmosphere to the ocean interior.
Onset of the spring bloom of ice algae is
typically limited by the availability of light,
and the current consensus is that a few
tens-of-centimeters of snow is enough to pre-
vent sufficient solar radiation to reach under-
neath the sea ice.
Given the unique conditions, a new study by
scientists at the Aarhus University, Denmark
comes as a surprise. The team has found that
the small ice algae on the underside of the
Arctic sea ice live and grow at a light level
corresponding to only 0.02% of the light at
the surface of the ice.
It is pitch dark all winter in the Arctic. And
even when the spring sun appears in the sky,
the compact ice and snow layer allows only
a tiny amount of light to penetrate into the
sea. Here, in this extreme environment where
temperatures are below the freezing point
and salinity is higher than in the sea water,
and where light penetration is extremely low
for a large part of the year, the ice algae are
found.
On the underside of the sea ice microscop-
ic algae have adapted to the very extreme
conditions prevailing here. Among these are
diatoms that reside on the underside of the
ice and in small channels in the ice – the so-
Scientists Devise
Interactive Microscope,
Unveil Physical Principles
of Cell Organization
Cell membranes, in addition to their struc-
tural-mechanical functions, regulate diverse
cellular functions, and play a significant role
in several physiological and pathological
processes.
The spatiotemporal organization of cells
largely depends on physical processes such
as diffusion or cytoplasmic flows, and strate-
gies to perturb physical transport inside cells
are not yet available.
Therefore, there is a need for a generic,
accessible analytical tool that can combine
full-lipidome quantification with simultane-
ous monitoring of the turnover, the flux, of
individual lipids.
Enter focused-light-induced cytoplasmic
streaming aka FLUCS. Developed by a
collaborative team of scientists at the Max-
Planck Institute for Cell Biology and Ge-
netics (MPI-CBG) and École polytechnique
fédérale de Lausanne (EPFL), scientists of the
Institute for Pancreatic Islet Research (IPI) of
Helmholtz Zentrum München in Dresden.
FLUCS is local, directional, dynamic, probe-
free, physiological, and is even applicable
through rigid egg shells or cell walls.
By making a microscope this interactive, the
team has found a way to induce and control
February 13th, 2018.
called brine channels, where heavier saline
water flows out of the ice and into the sea.
This light level measuring at 0.02 percent
of the light hitting the top of the ice and snow
on a sunny day wherein the algae was able
to thrive, is the lowest threshold for active
photosynthesis ever recorded.
“We worked on the sea ice in April-May,
where there was a meter of sea ice and a me-
ter of snow on top of the ice,” Lars Chresten
Lund-Hansen, a scientist with Aarhus Uni-
versity’s Arctic Research Center in Denmark,
said in a news release. “With special ice
corers we drilled holes in the ice so that we
could measure the ice algae on the underside
of the ice and collect samples.”
“Our measurements showed that the ice al-
gae began to grow at a light intensity below
0.17 μmol photons m-2 s-1. This corresponds
to less than 0.02% of the amount of light that
reaches the surface of the snow on a sunny
day,” says Kasper Hancke, currently work-
ing at the Norwegian Institute for Water Re- By Disha Padmanabha
search (NIVA) in Oslo, who was responsible
for the field work. show that ice algae may play an important ice receive more light,” Lund-Hansen said.
role much earlier in the spring in the Arctic “This may significantly impact the growth
The general view has been that ice algae do than hitherto assumed. of the algae and the extent of the ‘spring
not obtain sufficient light for growth when bloom.’ This new knowledge must be con-
they are covered by a more than 30-50 cm “Temperatures are rising in the Arctic. sidered in the puzzle of how the Arctic will
deep cover of snow and ice. The new meas- When the snow on top of the ice gets warm- respond to a warmer world.”
urements completely change that view and er, the algae residing on the underside of the
motion within living cells and early embry-
os- they were able to actively guide central
developmental processes in worm embryos.
Matthäus Mittasch, the leading author of
the study says: “With FLUCS, microscopy of
growing embryos becomes truly interactive“.
And indeed: with the help of realistic comput-
er simulations the researchers even managed
to reverse the head-to-tail body axis of worm
embryos with FLUCS, leading to inverted de-
velopment.
Lead investigator Moritz Kreysing, with
a dual affiliation to the Center for Systems
Biology Dresden, concludes: “The ability
to actively move the interior of biological
cells will help to understand how these cells
change shape, how they move, divide, re-
spond to external signals, and ultimately how
entire organisms emerge guided by micros-
cale motion.” On the medical side, FLUCS
has the potential to improve our understand-
ing of developmental defects, aid in-vitro fer-
tilization, organism cloning, and the discov-
ery of new drugs.
By Disha Padmanabha
9
February 13th, 2018.
Reassessing Discarded
Chemicals in Search of
New Antibiotics
The growing prevalence of antibiotic resist-
ance in pathogenic bacteria is severely erod-
ing our ability to manage bacterial infection.
Central to an effective response to this prob-
lem will be the development of novel anti-
bacterial drugs that display activity against
bacteria resistant to existing antibiotics.
In one of such quests, University of Leeds
scientists are taking time out to revisit
long-forgotten, discarded chemical com-
pounds to find if any of them possess any
requisite properties of an antibacterial drug.
By initiating the discovery process with
compounds about which something is already
known, including the fact that they possess
antibacterial activity, this approach offers a
potential fast-track through the challenging
early stages of discovery, write the scientists.
Dr Alex O’Neill, from the Antimicrobi-
al Research Centre at the University, said:
“We’re showing the value of reviewing
compounds previously put on the back of
the shelf. Amongst the 3,000 or so antibiot-
ics discovered to date, only a handful have
been brought into clinical use. There may be
a wealth of compounds out there with un-
tapped potential.
“At the moment, the bugs are outsmarting
the scientists, and we can’t allow that to con-
tinue. By studying compounds which past re-
search has shown already have antibacterial
USFDA Issues Second
Breakthrough Therapy
Designation for GSK’s
Meningitis Vaccine
GlaxoSmithKline’s meningitis B vaccine
Bexsero [Meningococcal group B Vaccine
(rDNA, component, adsorbed)] has now re-
ceived a Breakthrough tag for the prevention
of invasive meningococcal disease in chil-
dren ages 2 -10.
It is currently approved in the U.S. for peo-
ple aged 10 – 25 for which it had received
BTD for development in the prevention of
IMD in 2015. Bexsero is the first vaccine in
the world to receive the Breakthrough Thera-
py Designation (BTD) twice.
Invasive meningococcal B disease is the
leading cause of life-threatening meningitis
in the industrialized world. The disease can
develop rapidly in healthy populations and
can result in high morbidity and mortality.
The designation will expedite the devel-
opment and review of drugs and vaccines
that are intended to treat or prevent serious
conditions and preliminary clinical evi-
dence indicates that the drug or vaccine may
demonstrate substantial improvement over
available therapy on a clinically significant
endpoint(s).
Drugs and vaccines that receive Break-
through Therapy Designation are eligible for
all features of the FDA’s Fast Track designa-
tion, including more frequent communication
10
properties, there is scope for a potential fast-
track through the challenging early stages of
drug discovery. This approach could pave the
way for life-saving new drugs.”
A family of compounds, known as the ac-
tinorhodins, was originally identified in the
1940s and was pronounced as having weak
antibiotic properties, thereby not taken for-
ward for development into a drug.
But Dr O’Neill now claims that this chem-
ical was not fully appreciated at the time at-
tributable to how scientists at the time did not
fully differentiate the individual compounds
within the family when they examined them,
leading to a less than precise picture of their
properties. This prompted his team to divide
the family and select a specific compound
(y-ACT) for further evaluation, using an
array of 21st century approaches, to assess
its potential and to understand how it works
against bacteria.
Dr O’Neill and colleague Professor Chris
Rayner believe the compound is worth seri-
ous consideration as the basis for a new drug
to combat certain types of bacterial infec-
tions.
Dr O’Neill added: “y-ACT exhibits potent
antibacterial activity against two important
representatives of the ESKAPE* class of
pathogens, which are bacteria that have de-
with the FDA about the drug’s development
plan and eligibility for Accelerated Approval
and Priority Review, if relevant criteria are
met.
GSK Vaccines Chief Scientist Rino Rappu-
oli, who spent more than 20 years developing
Bexsero, said: “This designation emphasis-
es the importance of tackling big scientific
challenges like meningitis B and breaking
new ground in disease prevention through
approaches like reverse vaccinology. GSK is
committed to the pursuit of innovative vac-
cines that help protect against serious diseas-
es with significant unmet need.”
“Thirty-five percent of all meningitis B
cases in the U.S. occur in children under 11
years old. This designation is an important
step forward in meningococcal prevention
and extending the protection provided by
this vaccine to a vulnerable age group in the
U.S. We look forward to continuing to work
with regulators and public health partners
to make this vaccine available for them,”
Thomas Breuer, GSK Vaccines chief medical
officer said.
veloped the ability to ‘escape’ the action of
existing drugs.”
“A major challenge in tackling the problem
of antibiotic resistance is to discover new
drugs – our study shows that potentially use-
ful drug candidates can be ‘discovered’ from
amongst the antibiotics we already know
about. The weak activity previously pub-
lished for the ACT family as a whole prob-
ably explains why this group was not further
evaluated, and it is intriguing to think that
other potentially useful antibiotic groups are
languishing in obscurity in academic jour-
nals just needing expert review using modern
processes and equipment.”
Supporting Dr O’Neill’s work, Dr Jonathan
Pearce, Head of Infections and Immunity at
the Medical Research Council, said: “There
is an urgent need to discover new ways to
fight AMR and the scientific community is
leaving no stone unturned in its search for
new antibiotics. This includes revisiting
chemical compounds that were once shelved.
“Until recently, no new antibiotics had
been discovered for 25 years. Dr O’Neill’s
research is important: it’s providing another
way of looking for potential antibiotics and
could hold the key to uncovering options that
were overlooked before but may be incredibly
useful now.”
Another research in the university was led
by Dr Michael Webb, whose research focus-
es on a compound, called pentyl pantothena-
mide.
First introduced in the 1970s, it was found
to be able to stop the growth of E.coli but not
completely kill the bacteria, therefore was
Vol. 02 NO 7
deemed useless and was never taken into
clinical use. Scientists who first analysed
the compound did not understand how it was
able to stop the growth, but Dr Webb and his
team have proved it is driven by Vitamin B5,
which is used to metabolise energy.
Bacteria have to make B5 and a key part of
the machinery they use to do so is called the
PanDZ complex. Pentyl pantothenamide tar-
gets the PanDZ complex, preventing E. coli
from making Vitamin B5 and so starving it of
the means to grow.
Dr Webb said: “The results of our latest
studyopen up the possibility of designing new
drugs that use the same means to attack E.
coli, but in a more effective way.”
Dr O’Neill concludes: “Our findings un-
derscore the importance of revisiting unex-
ploited antibiotics as a potential source of
new antibiotic drug candidates. We now be-
lieve a comprehensive re-evaluation of such
compounds is worthwhile, potentially offer-
ing new ways to protect against infections.”
Each year, the Medical Research Coun-
cil spends approximately £6.5 million on
AMR-related research. With decades of
work, MRC researchers have pioneered inno-
vations in AMR research from mapping how
infections spread, discovering new resistance
mechanisms, and identifying new antibacte-
rial compounds.
The next frontier is to usher in a new class
of antibiotics to tame superbugs that have
steadily built resistance to our current arsenal
of therapies, including last-resort options to
fight multi-drug resistant bacteria.
By Disha Padmanabha
Vol. 02 NO 7
Mirror-Image Molecules
Clear the Deck for More
Durable Drugs
Proteins and peptides have a number of
properties that make them highly effective
as therapeutic agents. These include very
precise specificity, high binding affinity,
low toxicity, and low risk of drug–drug in-
teractions. Their diversity also provides very
broad coverage of disease targets.
Despite this, there are relatively few pep-
tide drugs approved—around 60—compared
with around 1,500 small molecule drugs- a
major obstacle being- proteins and peptides
are easily destroyed by proteases and, thus,
typically have prohibitively short half-lives
in human gut, plasma, and cells.
For reasons that are not fully understood
and which go back to the origin of life, al-
most all amino acids in the natural world oc-
cur in one geometric form. Their atoms are
arranged in such a way that makes the entire
amino acid molecule appear left-handed, or
“L” for short.
As a result, natural peptides are also
left-handed. Because peptides produced by
microbes, plants and animals can be harmful,
the human body has evolved efficient ways to
purge them. Wrap your head around this bril-
liant plan- if we could, let’s say, find a way
to rotate/inverse these molecules, not only
would they be right-handed amino acids,
which are also known as “D” for dextrorota-
ry, they would additionally bind to the same
Asparagine Found in Food
Linked to Metastasis of
Breast Cancer
Asparagine, a non-essential amino acid
named after the humble asparagus, has now
been discovered to drive the spread of breast
cancer in a CRUK study investigating wheth-
er a change in diet could help patients with
breast tumours.
The study “adds to a growing body of ev-
idence that suggests diet can influence the
course of the disease,” one of the study’s first
authors, Simon Knott, associate director of
the Center for Bioinformatics and Functional
Genomics at Cedars-Sinai Medical Center in
Los Angeles, said in a statement.
Most breast cancer patients do not die from
their initial tumour, but from secondary ma-
lignant growths (metastases), where cancer
cells are able to enter the blood and survive
to invade new sites. Researchers have shown
how limiting the body’s production of this
amino acid – a building block for larger pro-
tein molecules in the body – or curbing it with
drugs or dietary restrictions, significantly re-
duced the ability of breast cancers to spread.
The results have yet to be shown in human
trial, but after tests on mice, academics said
in future an asparagine restrictive diet and
treatment could be given after surgery to re-
move the primary tumour.
“Our work has pinpointed one of the key
mechanisms that promotes the ability of
breast cancer cells to spread,” said Professor
Greg Hannon, lead author of the study based
receptors they did earlier while sliding unno-
ticed past the body’s defense mechanisms.
And this is exactly what a team the Univer-
sity of Toronto has been able to achieve using
a purely computational approach.
The team, led by Philip Kim, a professor of
computer science and molecular genetics in
the Donnelly Centre for Cellular and Biomo-
lecular Research, has developed a new tech-
nology for making mirror-image peptides,
which bind and activate receptors on the sur-
face of cells.
“Mirror image peptides are not recognized
and degraded by enzymes in the stomach or
bloodstream and therefore have a long-last-
ing effect,” says Kim. The other advantage,
he said, is that mirror-image peptides also
get overlooked by the immune system, which
often mistakes natural peptides for foreign
invaders and thus limits drug efficacy.
The study created mirror-image versions of
existing drugs, which last longer in the body
because they’re harder to digest. For patients,
this would mean less frequent drug injections
and more medicines could potentially be
made available as pills.
The team was able to create these mirror
molecules of two blockbuster drugs, a diabe-
tes medication called glycogen-like-peptide
at the Cancer Research UK Cambridge In-
stitute. “When the availability of asparagine
was reduced, we saw little impact on the pri-
mary tumour in the breast, but tumour cells
had reduced capacity for metastases in other
parts of the body. In the future, restricting this
amino acid through a controlled diet plan or
by other means could be an additional part of
treatment for some patients with breast and
other cancers.”
The international team of cancer specialists
from Britain, the US, and Canada studied
mice with an aggressive form of breast can-
cer. The mice develop secondary tumours in
a matter of weeks and tend to die from the
disease within months.
In the course of their study, the team looked
at the genes that were switched on inside
each cell type, and found 192 that were
more active in those with a greater ability to
spread, called 4T1-T cells. When they then
compared gene data with similar information
from patient samples, the researchers found
the same genes were more active in people
with aggressive breast cancer. The research-
ers then used molecular tools to switch genes
off individually in 4T1-T cells and watched
how this affected their spread in Petri dishes
and mice. In both tests, switching off a gene
called asparagine synthetase stopped the
cells from spreading. As the name suggests,
this gene is responsible for making asparag-
1 (GLP1) and the thyroid drug parathyroid
hormone (PTH). And the results when ana-
lysed showed how these rotated forms had
longer effects on cells than the existing ver-
sion of these drugs.
In the study, the team started with the larg-
est public database which contains structural
information for three million helical pep-
tides. They then created an algorithm to flip
these peptides into their D versions. Finally,
the team looked in this new virtual library
of mirror-image peptides for those that best
matched GLP1 and PTH.
They computationally generated a D ver-
sion of every protein in the Protein Data
Bank (PDB), creating the D-PDB, and ex-
tracted the D-proteins’ α-helices into more
than 2.8 million separate database files. They
then used known drug-target interactions to
screen the helix database for D-helices with
binding features positioned similarly to those
of natural peptide and protein drugs. To cre-
ate matches for drugs that bind in complex
ways, the researchers made short D-strands
by retroinversion and used the strands to link
D-helices into three-part D-analogs.
Kim and coworkers used the method to cre-
ate D-analogs for GLP-1, a diabetes and obe-
sity treatment that targets the GLP-1 receptor,
ine in the body.
Breast tumours in mice made of the 4T1-T
cells were less able to spread when the mice
were treated with a leukaemia drug that chops
up asparagine. And the same result happened
when the researchers simply fed the mice a
low asparagine diet.
Professor Charles Swanton, Cancer Re-
search UK’s chief clinician, said: “This is in-
teresting research looking at how cutting off
the supply of nutrients essential to cancer’s
spread could help restrain tumours.
“The next step in the research would be to
understand how this translates from the lab
to patients and which patients are most likely
to benefit from any potential treatment.”
“This is one case where we can show at a
deep biochemical level how a change in diet
can impact properties of cells that are rel-
evant to the progression of lethal disease,”
said Hannon. “But of course, until human
February 13th, 2018.
By Disha Padmanabha
and parathyroid hormone, an osteoporosis
medication that hits the parathyroid receptor.
The D-analogs had about the same efficacy
as their natural counterparts in cells, although
the GLP-1 replacement required a higher
dose. And the D-analogs withstood the cells’
proteases for longer than the natural peptides.
“We are now investigating whether the
D-PTH could be orally delivered because it
is avoiding breakdown in the stomach”, says
Kim. “For frequently dosed medication, this
is of great interest, as taking a pill is much
easier than having an injection. This could
lead to many more peptide drugs being taken
as pills.”
Kim is currently working with the U of T
patent office to protect his technology as he
explores opportunities to partner with the
pharmaceutical industry to commercialize the
research. He is also developing mirror-image
versions of peptides that work against the
Dengue and Zika viruses in order to make
them more durable in the bloodstream.
“We are testing our approach on as many
interesting peptides as we can,” Kim said.
By Disha Padmanabha
studies are done, this isn’t a DIY method to
prevent cancer.”
Baroness Delyth Morgan, chief executive
of Breast Cancer Now, said: “This early dis-
covery could offer a long-awaited new way
to help stop breast cancer spreading – but we
first need to understand the true role of this
nutrient in patients. With nearly 11,500 wom-
en still dying from breast cancer each year in
the UK, we urgently need to stop the disease
spreading around the body, where it becomes
incurable.
“On current evidence, we don’t recom-
mend patients totally exclude any specific
food group from their diet without speaking
to their doctors. We’d also encourage all pa-
tients to follow a healthy and varied diet –
rich in fruit, vegetables and pulses, and lim-
ited in processed meat and high fat or sugar
foods – to help give them the best chance of
survival.”
11
February 13th, 2018.
Altruistic Immunity Could
be an Interesting Approach
to Tackle Malaria
Malaria kills roughly twice as many people
worldwide as AIDS, drugs no longer work
against some strains, and mosquitoes in di-
verse parts of the United States now carry the
disease.
When the malaria-causing Plasmodium
falciparum enters the body through female
anopheles mosquito, a subsequent immune
response can result in the production of an-
ti-parasitic antibodies. These acquired anti-
bodies could be ingested by other Plasmo-
dium-harboring mosquitoes, inhibiting the
survival and transmission of the parasite.
Attributable to this pathway, an estimat-
ed 1 in 25 malaria patients are able to stop
the spread of malaria, conferring a type of
altruistic immunity- says a recent study by
scientists led by researcher Teun Bousema
at Radboud university medical center. This
is observed more prominently among mis-
sionaries who had been infected with malaria
several times.
“This is the first time that we have been
able to produce direct evidence that human
antibodies against malaria parasite proteins
are able to prevent the spread of malaria”
said Bousema.
This study examined blood from more than
600 malaria patients, testing their ability to
inhibit mosquito infection and their immune
response to over 300 malaria proteins: An-
www.biotecnika.org
12
Vol. 02 NO 7
tibodies targeting 45 of these proteins were
linked with people’s ability to inhibit the
spread of malaria, and people with these an-
tibodies were ten times less infectious for
mosquitoes.
The results mean better understanding of
how people contribute to the spread of malar-
ia. The team is now investigating roles of a
number of proteins as to their potential in the
transmission blocking malaria vaccine.
Bousema: “We have developed a malaria
parasite that expresses a firefly gene, allow-
ing us to see just by looking at the mosquito
whether or not it has been infected.”
PhD student Will Stone who has studied
people’s immune response to over 300 ma-
laria proteins says, “We saw that our test
subjects produced antibodies that are able to
slow the spread of malaria in response to 45
of these proteins. People with these antibod-
ies were ten times less likely to infect mos-
quitos.”
Bousema concludes, “This research ena-
bles us to better understand which patients
prevent the spread of malaria. We are now
looking at whether it is possible to develop a
malaria vaccine using some of these proteins.
A vaccine that prevents the spread of malaria
would help reduce the disease burden of ma-
By Disha Padmanabha
laria worldwide.”