Penicillin Now Exposed

By: Gabe Neiderer

Introduction
In todays society we have a large variety of antibiotics for combating bacterial diseases. Penicillin was
the first antibiotic to be discovered and has since developed into a large category of antibiotics in use
today. Some of the penicillin types in use today are penicillin V, penicillin G, procaine penicillin, and
benzathine penicillin. Derivatives of the penicillin bacterial culture are ampicillin, amoxicillin, and
flucloxacillin. All of these drugs have one purpose for which they were created, to either kill bacteria or
inhibit the growth of bacteria. The interesting part about these drugs is that they are all similar in
structure, but because of one small part that is different they can have different effects. All of these
drugs will be mentioned throughout the document.
History and Development
Alexander Fleming was fortunate enough to discover penicillin by mistake
back in 1928. Fleming had, accidently, left a plate of Staphylococcus bacteria
open over night. When he returned there was a mold growing on the plate
and he noticed a ring around the mold of no bacterial growth. He cultured
some of the mold and discovered it to be Penicillium mold. He revealed that if
penicillin rubens were grown in the appropriate substrate the mold would
leave behind a substance that was antibiotic in nature, which he termed as
penicillin. He studied the mold and uncovered that this mold works best for
treating Gram positive bacteria that contained a thick peptidoglycan layer,
seen in Figure 1. The problem was is that he couldnt get the penicillin to last
long enough in the body.
It wasnt until two years after his discovery that someone had first used penicillin to sure an illness. Cecil
George Paines first successful curing was to a gonococcal infection in an infant on November 1930.
Then he moved on to treating eye infections; one in an adult and three more in infants, he cured all of
them. Other scientists worked on the in vivo bactericidal effects of penicillin. This specific group was
able to prove that it was harmless and effective for mice. When they moved on to the human treatment
they failed because they did not have enough volume of the penicillin to affect the body.
Beyond a few cases being cured occasionally no one had figured out a practical medical method to use
for this antibiotic. A world wide search was completed in 1944 for the best strain of penicillin, to make
the antibiotic from, and was found on a moldy cantaloupe in Peoria, Illinois. With the strain found the
U.S. government was able to produce 2.3 million doses in time for the invasion of Normandy, France.
The war forced progress to be made due to the demand created by the soldiers and public. By June of
1945 the U.S. was producing over 46 billion units per year. Even with mass production happening as it
was there was still a high demand for the drug because it can only last in the human system for three to
Figure 1
four hours. The penicillin molecules in the body are targeted as foreign molecules and transporters take
them to the kidneys to be excreted. Nobody could find a molecule that could compete with the penicillin
uptake by these transporter molecules until the probenecids were found. This molecule gets absorbed
by the transporters over the penicillin which increases the amount of time penicillin is in the body,
therefore giving it more time to fight the infection. This also lowered the amount of times someone
needed to receive treatment and lowered the amount needed for each dose, all of which balanced out
the demand for this drug.
Structure and Function
The chemical structure of penicillin is used by scientists to categorize antibiotics iin or out of the
penicillin family. All types of penicillins and its derivatives follow this formula, R-C
9
H
11
N
2
O
4
S. The R
part of the chain is a component of the compound that can be changed. Each of the types of penicillin
and the derivatives has their own specific R group that is added to base structure of the compound.
Since the drugs only changes at one spot on the central four member ring
(as seen in Figure 2) it is the common ring structure that links them all
together. If a scientist would ever be analyzing a molecule and saw the ring,
known as a Beta- Lactam ring, they would know it belongs to the penicillin
family.
The penicillin molecule is extremely clever in its process to destroy bacteria.
The Beta-Lactam ring (BLR) interacts with the peptidoglycan layer of gram
positive bacteria cell wall. Only when the bacteria is dividing and breaks
down this layer can the penicillin move in and attach to the terminal acid residues on the inside of the
layer.
This attachment is irreversible and prevents transpeptidase from forming the cross link on those
terminal amino acids, seen in Figure 3. Without the cross links the peptidoglycan layer cannot reform to
protect itself from the human bodys defenses. The bacterial cells are
then picked up by either a macrophage or dendritic cell to be broken
down and start the process of making antibodies to that specific
bacterium. Penicillin V is the oral pill form of the drug that most
people are familiar with and uses the process above. In fact penicillin
G, procaine penicillin, and benzathine penicillin all use the same
method as the oral pill and attack the cross links. The other penicillin
derivatives all inhibit the formation of the cell wall or the
peptidoglycan layer as well, but they attack a different part than
traditional penicillin. Table 1 below lists the uses of penicillin and the
uses of the penicillin derivatives.


Figure 2
Figure 3
Name Purpose
Penicillin G Penicillin in IV
Procaine Penicillin Intramuscular penicillin
Benzathine Penicillin Intramuscular Penicillin
Ampicillin Treats a wider spectrum of bacteria than penicillin
Amoxicillin Similar to penicillin just different target on cell wall
Flucloxacillin Used to treat penicillin resistant bacteria

Penicillin Today
Today doctors still use penicillin to treat bacterial infections such as tonsillitis and infections of the ears,
throat, and lungs. Penicillin can also aid peoples immune systems when the system is weakened by
illness, injury, or receiving treatment that could damage the immune system. But today through over
use and people not properly taking their medication many penicillin resistant bacteria have emerged. .
This demand drove the creation of the penicillin derivatives such as ampicillin and flucloxacillin that
could affect a wider spectrum of bacteria. These two were able to inhibit bacterial cells that produced
Beta-Lactamase, which blocks the antibiotic from interacting with the bacteria, therefore could affect
more bacteria than penicillin. Also the development of antibiotics that could inhibit gram negative
bacteria became available through manipulating the molecular structure of penicillin. Incredible
advances in medicine have been made available to us all because of this one little mistake a random
scientist made back in 1928.
Table 1