Is there such a thing as an "evolution-proof" drug? (part the third)

A claim that scientists need to quit making:

I've written about these types of claims before. The first one--a claim that antimicrobial peptides were essentially "resistance proof," was proven to be embarrassingly wrong in a laboratory test. Resistance not only evolved, but it evolved independently in almost every instance they tested (using E. coli and Pseudomonas species), taking only 600-700 generations--a relative blip in microbial time. Oops.

A very similar claim made the rounds in 2014, and the newest one is out today--a report of a "super vancomycin" that, as noted above, could be used "without fear of resistance emerging." (The title of the article literally claims "'Magical' antibiotic brings fresh hope to battle against drug resistance", another claim made in addition to the "no resistance" one in the Scripps press release by senior author Dale Boger). This one claims that, because the modified vancomycin uses 3 different ways to kill the bacteria, “Organisms just can’t simultaneously work to find a way around three independent mechanisms of action. Even if they found a solution to one of those, the organisms would still be killed by the other two.”

A grand claim, but history suggests otherwise. It was argued that bacteria could not evolve resistance to bacteriophage, as the ancient interaction between viruses and their bacterial hosts certainly must have already exploited and overcome any available defense. Now a plethora of resistance mechanisms are known.

Within the paper itself, the limitations are much more clearly laid out. Discussing usage of the antibiotic, the authors note of these conventional semisynthetic vancomycin analogs:

"However, their use against vancomycin-resistant bacteria (e.g., VRE and VRSA), where they are less potent and where only a single and less durable mechanism of action remains operative, likely would more rapidly raise resistance, not only compromising its future use but also, potentially transferring that resistance to other organisms (e.g., MRSA)."

So as they acknowledge, not really so resistance-proof at all--only if they're used under perfect conditions and without any vancomycin resistance genes already present. What are the odds of that once this drug is released? (Spoiler alert: very low).

Alexander Fleming, who won the 1945 Nobel Prize in Physiology or Medicine, tried to sound the warning that the usefulness of antibiotics would be short-lived as bacteria adapted, but his warnings were (and still are?) largely ignored. There is no "magic bullet;" there are only temporary solutions, and we should have learned by now not to underestimate our bacterial companions.

Part of this post previously published here and here.

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Dear Tara,

If I am not mistaken, the part of the paper you quote refers to conventional semisynthetic vancomycin analogs which are already in the clinic (with their single effective mechanism of action against VRE) rather than the most promising compound 18 (with three effective mechanisms of action against VRE) that the authors synthesised.

Furthermore, the resistance experiments carried out by the authors (Figure 10) are done with VRE, meaning the vancomycin resistance genes are in fact already present?

I am intrigued to hear your thoughts on the paper considering these two points. Personally, I see the results from the paper as promising although I agree that the use of the term "resistance-proof" is seriously problematic.

Kind regards,
Sophie

This was a very interesting post! I have a question regarding Fleming's theory. Did he think that the use of antibiotics wouldn't be able to be used for a long period of time due to the bacterial resistance? Wouldn't that be congruent with the blog post about having temporary treatments since bacteria can always figure out how to become resistant? Thanks for your clarification.

By Carly Hill (not verified) on 07 Jun 2017 #permalink

In the future do you think we will ever come up with a "resistant proof" antibiotic or will the bacteria always adjust no matter what we find??