The Antibiotic Wars

In
A
Galaxy
Far
Far Away
…..
Not really!
Back in 1928…

A biologist by the name of Alexander Fleming, who revolutionized the world of Biology with the discovery of Penicillin was working on a colony of Bacteria. Probably he was bored of working with Bacteria and he went off on a vacation. Upon returning back from his trip, he realized that the bacteria he was meaning to throw away had died.

Why did these bacteria die? He wondered. Rather than ignoring the dead bacteria he went on to find an answer for their death. After some time Fleming realized that some of the bacterial colony had been contaminated by a Mold (Fungus). With further research on the subject he figured it out that the mound was a Penicillium based mound.

Eureka! Antibiotic was discovered!!!

Alexander Fleming gave that Antibiotic the name “Penicillin” because of its derivation from the mound Penicillium. With the discovery of Penicillin half of the world’s problem related to diseases were solved. By the year 1942 the Penicillin was purified and synthesized in the large scale, within 1945 the Penicillin had reached all over the world.

Everything was going good, but a necrotizing bacteria called the ‘Staphylococcus aureus” became resistant to Penicillin! “Whoa” right?

Yes! Whoa!

But how?

Yes, How! That’s a good question!

The bacteria managed to pick up a Transposons, also known as “The Jumping Genes” which could encode β-Lactamase an enzyme that breaks the Lactam ring which is in Penicillin, while doing so it makes the Penicillin inactive. Within a short period of time “Staphylococcus aureus” became resistant to Penicillin. How did that happen? Well for that we have to go back to the 1859 AD.

Origin of Species by Natural Selection:

Charles Darwin explained about many things in his book, most of which are mistakenly understood even till now. But the main theme of his “Theory of Evolution” was Natural Selection.

So what is Natural Selection?

In the simplest of explanation, Natural selection is the process where an organism adapts to the changing environment. Natural selection is the basic mechanism of Evolution. How does that work with our Bacterial populations?

Here’s how!

So we had a normal strain of Staphylococcus aureus, which was now subjected to Penicillin. Mutation, another mechanism for Evolution is ubiquitous in the nature, our Staphylococcus aureus managed to pick up the transposons to code for β-Lactamase, which meant that it was now resistant to Penicillin. But, the rest of the strains, which “didn’t” pick up the transposons were killed by the Penicillin. But since the Staphylococcus aureus which picked up the transposons was unaffected by the Penicillin and hence it survived and reproduce, where are the other strains died! – Survival of the fittest! Voila!

Antibiotic resistance is based on the phenomenon of Evolution by Natural Selection, and so far is the only process where we can observe “Evolution in real life”. Because, Evolution is a gradual process and takes many generations to complete, but our bacteria reproduce at higher rate so it’s easier to observe the changes, mutations (positive and negative) and see them evolve over time.

Over the time, many bacteria started getting resistant to different Antibiotics, and it takes a long time to make a new dose of antibiotic but the bacteria can evolve into a new strain in less than a year or two. But the bacteria, well they can evolve super-fast. That’s where the problem in antibiotic resistance comes, we may fall behind in the production of new and better antibiotics, but even with that the bacteria will evolve no matter how much we try!

Different bacteria have different type of resistant genes, for instance, I talked about the gene that encodes production of β-Lactamase, which in turn break the Lactam ring of the Penicillin and makes it inactive. So basically the proteins that has been translated from mRNA becomes the structure or enzymes that will help the bacteria become resistant to Antibiotics. Such process occurs as a result of Antibiotic Resistant Genes which occur in the Plasmids, which forms polypeptides which in turn becomes Antibiotic degrading enzymes (for e.g. β-Lactamase).

A second method can be, the production of Efflux pump. So what happens in this case is some bacteria can produce an Efflux pumps, which lies in the membrane, when some antibiotics inhibits bacterial protein synthesis, the bacteria can pump out the antibiotics from within the cells to the outside using the Efflux pumps. Since the Antibiotics are pumped out, the antibiotics won’t have any effect on the Bacteria.

While some of the other Bacteria use different methods, one such example is the modification of the Antibiotic binding sites. Antibiotics have binding sites, for instance, the β-Lactam (Penicillin) binds to the Penicillin binding site found in the Peptidoglycan layer of the Bacteria. But some bacteria with that genes can modify the binding site can change the structure of the protein which making the Penicillin unable to bind to its respective binding site. Such type of resistance is found in the bacteria MRSA or Methicillin-resistant Staphylococcus aureus. So in this case, the Antibiotic- Methicillin wouldn’t work on the MRSA.

But the fun thing is, with removal of the selective pressure on the bacteria over time, the susceptibility to some antibiotics can return within some bacteria. Once the environment is back to normal, the bacteria can return back to their normal strain, which makes the previous dose of Antibiotics effective as well. A similar evolutionary event happened in England, during the pre and post Industrial revolution era. For that you can read my article on What Darwin Saw?

Such genes are then transferred from one bacteria to another via Transduction, Conjugation.

So that’s why it’s better to avoid taking Antibiotics for smaller problems. Some people take Antibiotics for everything and consume them as if they’re eating popcorn while watching a movie!