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posted by martyb on Sunday June 07 2020, @01:18PM   Printer-friendly
from the good-news-for-a-change dept.

'Poisoned arrow' defeats antibiotic-resistant bacteria: A dual-mechanism antibiotic kills Gram-negative bacteria and avoids drug resistance (SD)

Poison is lethal all on its own — as are arrows — but their combination is greater than the sum of their parts. A weapon that simultaneously attacks from within and without can take down even the strongest opponents, from E. coli to MRSA (methicillin resistant Staphylococcus aureus).

A team of Princeton researchers reported today [DOI: 10.1016/j.cell.2020.05.005] [DX] in the journal Cell that they have found a compound, SCH-79797, that can simultaneously puncture bacterial walls and destroy folate within their cells — while being immune to antibiotic resistance.

[...] "This is the first antibiotic that can target Gram-positives and Gram-negatives without resistance," said Zemer Gitai, Princeton's Edwin Grant Conklin Professor of Biology and the senior author on the paper. "From a 'Why it's useful' perspective, that's the crux. But what we're most excited about as scientists is something we've discovered about how this antibiotic works — attacking via two different mechanisms within one molecule — that we are hoping is generalizable, leading to better antibiotics — and new types of antibiotics — in the future."

[...] To prove its resistance to resistance, Martin tried endless different assays and methods, none of which revealed a particle of resistance to the SCH compound. Finally, he tried brute force: for 25 days, he "serially passaged" it, meaning that he exposed bacteria to the drug over and over and over again. Since bacteria take about 20 minutes per generation, the germs had millions of chances to evolve resistance — but they didn't. To check their methods, the team also serially passaged other antibiotics (novobiocin, trimethoprim, nisin and gentamicin) and quickly bred resistance to them.

Proving a negative is technically impossible, so the researchers use phrases like "undetectably-low resistance frequencies" and "no detectable resistance," but the upshot is that SCH-79797 is irresistible — hence the name they gave to its derivative compounds, Irresistin.

Journal Reference:
James K. Martin, Joseph P. Sheehan, Benjamin P. Bratton, et al. A Dual-Mechanism Antibiotic Kills Gram-Negative Bacteria and Avoids Drug Resistance. Cell, 2020; DOI: 10.1016/j.cell.2020.05.005


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  • (Score: 5, Insightful) by Azuma Hazuki on Sunday June 07 2020, @09:37PM (4 children)

    by Azuma Hazuki (5086) on Sunday June 07 2020, @09:37PM (#1004618) Journal

    My big fear about phage therapy is that, although viruses technically aren't alive, they do still have nucleic acids and as such are prone to random mutation, genetic drift, and all the other natural selection processes "really living" organisms are. Who is to say one of these things won't mutate in such a way that it develops a taste for mammalian cell walls rather than, say, gram-negative lipopolysaccharide shells?

    --
    I am "that girl" your mother warned you about...
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  • (Score: 2) by Reziac on Monday June 08 2020, @05:39AM (2 children)

    by Reziac (2489) on Monday June 08 2020, @05:39AM (#1004738) Homepage

    You're a scary person, you know that :)

    https://en.wikipedia.org/wiki/Phage_therapy#Safety [wikipedia.org]

    So far only certain strains, but sure indicates a potential for trouble.

    --
    And there is no Alkibiades to come back and save us from ourselves.
    • (Score: 2) by Azuma Hazuki on Wednesday June 10 2020, @12:25AM (1 child)

      by Azuma Hazuki (5086) on Wednesday June 10 2020, @12:25AM (#1005549) Journal

      Why am I scary, for pointing out the very real possibility of creating a permanent pandemic of flesh-eating viruses? This world belongs to microbes; we multicellular aberrations are relative newcomers and are incredibly complicated and fragile by comparison.

      --
      I am "that girl" your mother warned you about...
      • (Score: 2) by Reziac on Wednesday June 10 2020, @01:16AM

        by Reziac (2489) on Wednesday June 10 2020, @01:16AM (#1005572) Homepage

        Did you not see the smiley? Speaking from a background in microbiology, I thought you made an excellent point.

        --
        And there is no Alkibiades to come back and save us from ourselves.
  • (Score: 1, Informative) by Anonymous Coward on Monday June 08 2020, @11:46AM

    by Anonymous Coward on Monday June 08 2020, @11:46AM (#1004794)

    Who is to say one of these things won't mutate in such a way that it develops a taste for mammalian cell walls

    That's why you have your immune system. It kills these things on regular basis.