Antimicrobial Resistance

Stalling The More Permanent Future Pandemic We Still Can Prevent

How do bacteria become resistant in the first place?

The probability of a mutation in a specific position in a bacterial genome while replication occurs is 10^-10 per genome per replication. That seems minuscule – something that should hardly be a problem.

Schematic of the mazEF toxin-antitoxin (TA) system

The Transposon

Transposons are self-automated pieces of DNA. I think of them as biological robots. They are pieces of DNA that excise (cut themselves) out of a particular bacterial sequence, form a short, circular piece of DNA called a plasmid, and then reinsert themselves into the genome of another bacteria.

The Notorious Efflux pump

An efflux pump is like the whole that you might find at the bottom of a plastic water bottle you’re trying to fill up.

Mutating the target

The last mechanism that I’d like to discuss is the most direct mechanism for resistance. Given a particular protein that is targeted by a small molecule, bacteria mutate that target, which results in a small molecule that has little to no affinity for the new mutant.

Part 2 — Existing antimicrobial resistance solutions and limitations

The most obvious solution to the problem of antibiotic resistance is to keep developing them. That’s the approach the scientific community is, for the most part, taking right now. Once a target becomes irrelevant due to the transfer of an antibiotic resistance determining factor, you choose a new target and start the process all over again. Each cycle of developing a new antibiotic and then bacteria getting resistant to the antibiotic takes only a few years (In the lab, bacteria often take no more than a few hours to develop resistance to a drug, but obviously the selective pressure in the lab is much higher than that in nature. More on that here.)

Part 3 — future directions for the field of antimicrobial resistance

Works Consulted

Munita, J. M., & Arias, C. A. (2016). Mechanisms of Antibiotic Resistance. Microbiology spectrum, 4(2), 10.1128/microbiolspec.VMBF-0016–2015. https://doi.org/10.1128/microbiolspec.VMBF-0016-2015

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Mukundh Murthy

Innovator passionate about the intersection between structural biology, machine learning, and chemiinformatics. Currently @ 99andbeyond.