Eukaryotic Microbial Diseases

Eukaryotic Diseases Present Extra Challenges

Because bacteria and other prokaryotes use very different proteins

and mechanisms for maintaining their cells vitality than humans do, it
is relatively easy to design drugs that will interact with the bacterial
targets, but will not interact with the analogous proteins and other
molecules in humans
The proteins and mechanisms used by eukaryotic pathogens to
maintain their vitality are more similar to those we use to maintain our
vitalitythe potential for cross-reactivity and side effects is greater

Protozoans Are Our Most

Common Eukaryotic Pathogens
Most fungi that inhabit the human body are commensals, but can be
opportunistic, and take advantage of factors such as a shift in the microbial
environment, pH, or suppressed immune system function
Fungi often cause skin infectionsathletes foot, ringworm, jock itch

CandidaAn Opportunistic
Fungal Pathogen
Thrushinfected patches in
the oral mucous membranes

Candida infection in the

thumbnail

Transmission Can Be By Direct Contact

Or Through Vectors
Ex. growth of the Ophiostoma novo-ulmi fungus that causes Dutch
elm disease clogs up the water-carrying tubes in the trees xylem,
which kills the tree
If two elms stand close enough together for their roots to touch, the
fungus can move from one trees roots to the other
Burrowing beetles burrow into the dead tree and lay their eggs; when
the young hatch out, they fly out of the tree covered in fungal spores,
which are reproductive cells that can survive in harsh environments
for a time
The beetles carry the spores, then transmit them to other trees when
they bore into them

Transmission Can Be By Direct Contact

Or Through Vectors
Some have simple life cyclesthey complete their life cycle within a
single species
Ex. the diarrhea-causing protozoan Giarida lamblia Forms cysts,
protected by a special cell wall, that are ingested in food or water
Once ingested, the excystation produces trophozoites, which replicate
in the small intestine
The trophozoites form cysts in the large intestine, to be excreted in
the feces

Transmission Can Be By Direct Contact

Or Through Vectors
Some have complex life cyclesthey undergo different phases of
their life cycle in different hosts
Ex. the protozoan that produces malariaReplicates sexually in the
mosquito (the definitive host)
Transmitted to a human (the intermediate host) through bites, in
which it replicates asexually and differentiates

Plasmodium Falciparum Has A

Complex Life Cycle

Pathogens Need To Attach

Some use special

structures, ex. the diarrheainducing Giardia lamblia
has a ventral disk that it
uses to adhere to the cells
that line the small intestine

Pathogens Need To Attach

The malaria-inducing protozoan Plasmodium falciparum forms merozoites

in the human liver; they use merozoite surface proteins to attach to and
penetrate human red blood cells

Pathogens Take Advantage Of A

Compromised Immune System

Opportunistic pathogens only invade when the hosts immune system has
been compromised, ex.
When people are given immunosuppressive drugs for organ transplants
People who have autoimmune diseases
When antibiotics kill beneficial bacteria
As a side effect of other infections, such as HIV reducing the effectiveness
of CD4+ helper T cells

Pathogens Take Advantage Of A

Compromised Immune System

Ex. Patients with HIV infections often are also infected by the protozoan
Toxoplasma gondii , which is often acquired from cats
Pneumocystis jirovecii is a fungus that inhabits the human lung; many
people have antibodies against it in their bloodstreampeople with HIV
often get infected by it
Ex. The fungus Candida albicans is a commensal fungusit inhabits the
human mouth, throat, rectum and vaginaOne of the side effects of
antibiotics can be thrush (in the mouth and throat), finger/toe nail infections
or vaginal yeast infections

Pathogens Need To Evade

The Hosts Immune System

Some pathogens constantly change their cell surface molecules to evade

host detectionthis can even allow the pathogen to reinfect someone who
has already acquired an immunity to that pathogen
Ex. Trypanosoma bruceii cells are coated with a single glycoprotein, but it
changes (referred to as a variable surface glycoprotein)
The T. bruceii genome has thousands of genes that encode the surface
glycoproteinit turns one on at a time

Pathogens Need To Evade

The Hosts Immune System
The sleeping sickness is cyclical
The hosts immune system kills a lot of the invaders, and the person gets
better
However, by the time the first immune response has had time to mount an
effective defense, the remaining pathogens are expressing a different cell
surface glycoprotein, and the hosts immune system has to recognize them
and mount a new immune response to them (any memory cells it has dont
recognize the new glycoprotein)
The pathogens with the new surface antigen thrive, and the person gets
sick again

The Pathogen Needs To Nourish Itself

Many fungi secrete enzymes that break down host tissues and provide
nutrients for the fungus
Ex. Plant fungi (phytopathogenic fungi) secrete enzymes that degrade the
major components of cell walls:
cellulases (digest cellulose)
pectinases (digest pectin)
proteases (digest proteins)
xylanase (digests hemicellulose)

The Pathogen Needs To Nourish Itself

Other fungi physically force their way into the host cell
Ex. the fungus Magnaporthe grisea, which causes rice blastretains a lot of
water, producing a lot of internal pressure
Some of the hyphal cells are called apressoriathey grow structures called
penetration pegs which, backed by the high intracellular pressure, penetrate
the host cells

Apressoria And Penetration Pegs

Hypha

The Pathogen Needs To Nourish Itself

Pathogens often deprive the host of a critical nutrient

Ex. The malaria-causing protozoan Plasmodium falciparum cannot
synthesize purine bases (adenine and guanine); it penetrates the hosts red
blood cells, lives inside them and takes purines from the host cells
cytoplasm
This would prevent a cell from synthesizing nucleic acids, ATP, GTP and
other important molecules

They also consume the hosts hemoglobin, releasing heme, which is

cytotoxic

Eukaryotic Microbes Produce A

Variety Of Toxins

Some produce HC-toxin, which inhibits histone deacetylases (HDACs)

HDACs remove acetyl groups from histones, thereby turning genes off
HC-toxin leaves the host unable to turn certain genes off

Eukaryotic Microbes Produce A

Variety Of Toxins

The Amanita mushrooms produce alpha-amantin, which binds to RNA

polymerase II, the enzyme that generates most protein-coding mRNAs
The Amanitas RNA polymerase II is resistant to the toxin
This is an intoxication, not an infection

Eukaryotic Microbes Produce A

Variety Of Toxins

Some marine dinoflagelates (algae with two flagellae), cyanobacteria

and algae produce toxins that create what is known as harmful algae
blooms (slang term = red tide), which kills fish, birds and mammals
induces paralysis in humans
These toxins (ex. saxitoxin) block sodium channels, preventing nerves
from firing, resulting in flaccid paralysis
These are thought to defend the microbes against predatorsthe
microbes increase toxin release when they sense the presence of a
predator

Evolution Of Eukaryal Pathogens

And Their Hosts
Some acquire toxin-producing genes through lateral gene transfer

The host may evolve as wellex. fruit flies that breed in Amanita
mushrooms have evolved resistance to alpha-amanitin
They get covered with it, which protects them from parasitic worms

Good Review Questions From This Unit

Chapter 23 Application Questions1-4, 7, 8