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'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
(Score: 0) by Anonymous Coward on Monday June 08 2020, @10:35PM (1 child)
i think the real benefits of "antibiotics" over phages are only that antibiotics are "broad spectrum" (in comparison), with long shelf life.
thus one can give two or three anti biotic capsules to soldiers which he can store in his belt and send him/her? of into whatever mess they will encounter.
for phages, which are very specific(?) one needs to "grow" them first.
i suspect that there is a (secret) method to "replicate" the correct phages which isn't much more difficult than making kevir or joghurt if one has a sample with the target bacteria in the right "medium".
one can argue that milk without access to the "universal sphere of bacteria" (example your garden) will never good bad or turn into kevir or joghurt so in the same sense there must be a "universal sphere of phages" floating around to serve as starter. if this is the case then we have to cultivate a "library" of phages, which is costly and difficult.
however, i am tending to a so-far unscientific explanaition that the bacteria carries within itself all the ingridients for it's own doom. it is this "secret" that would allow a "healthy" non phage infected bacteria to "go wrong" and explode into phages. even if phages come from the outside, new phages made from infected bacteria consist 100% from bacterial materia.
it stands to reason, then, that it is a bacteria that infects a bacteria AFTER it has gonne thru a transformation.
i suspect that the phage already exists inside a healthy bacteria (is it a duck or a rabbit!).
(Score: 2) by Azuma Hazuki on Wednesday June 10 2020, @12:33AM
...are you aware that a 'phage in this case is a virus? It's not a bacterium which invades another bacterium.
I am "that girl" your mother warned you about...