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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: 3, Informative) by Anonymous Coward on Sunday June 07 2020, @04:58PM (9 children)
Probiotics aren't really enough, probiotics will help a bit in terms of pushing things back towards the previous balance, but only if the ecosystem hasn't been completely trashed to begin with. What's more, you need a lot of probiotics to make much of a difference.
The better thing to do is to just admit that conventional antibiotics are rarely an appropriate answer to the problem. They're for a few strains of bacteria like E. Coli 156 where a few cells per mL of fluid can be enough to destroy the liver. In situations like that, carpet bombing the body with antibiotics is a reasonable way of addessing the issue. But, still without serious problems.
Biologists have known for decades that you can target specific strains of bacteria by using phages resulting in little, if any, disruption to the other bacteria in the body. It's already in the food supply and has been for years, it just hasn't been used in humans in the US.
(Score: 5, Interesting) by NotSanguine on Sunday June 07 2020, @07:20PM (2 children)
That's absolutely true. However, the number and type of bacterial infections for which effective bacteriophage antagonists exists is quite limited.
As such, Phage therapy [wikipedia.org] is (and has always been) of limited utility. While antibiotics have their issues, not least of which is bacterial resistance, they are a class of treatments which have saved hundreds of millions of lives since Penicillin was introduced.
Nobody really thinks about it these days, but before antibiotics, a cut on your hand could (and sometimes did) kill you if the wound became infected. An abscess [wikipedia.org] was a potential death sentence.
Despite the problems with antibiotics, they are perhaps the most effective medical therapy ever devised.
If the research mentioned in TFA can be refined into an effective, targeted antibacterial agent, that would be wonderful. But until that (or some other mechanism) happens, antibiotics will continue to be an important treatment option for bacterial infections.
No, no, you're not thinking; you're just being logical. --Niels Bohr
(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...
(Score: 5, Insightful) by Azuma Hazuki on Sunday June 07 2020, @09:37PM (4 children)
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...
(Score: 2) by Reziac on Monday June 08 2020, @05:39AM (2 children)
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)
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
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
That's why you have your immune system. It kills these things on regular basis.
(Score: 3, Interesting) by Immerman on Monday June 08 2020, @04:45PM
Depends on the kind of probiotics. Fecal transplants from a healthy donor seem to have a pretty phenomenal track record of rapidly restoring a healthy gut biome.