'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: 4, Touché) by Anonymous Coward on Sunday June 07 2020, @01:21PM (7 children)
It's all very well inventing new compounds, but nothing works as well as good old-fashioned bleach in the lungs.
(Score: 3, Informative) by takyon on Sunday June 07 2020, @01:47PM (5 children)
It needs to be mixed with ammonia for extra effectiveness.
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(Score: 3, Touché) by The Mighty Buzzard on Sunday June 07 2020, @02:01PM (1 child)
Nah, hydrogen peroxide. That produces lots of oxygen. Has to be good for the lungs if that's the case, yeah?
My rights don't end where your fear begins.
(Score: 1, Informative) by Anonymous Coward on Sunday June 07 2020, @07:03PM
No. No. No. Not hydrogen peroxide! Sodium hydroxide. I know, it's easy to confuse them, with the whole 'oxide' thing, but sodium hydroxide has wonderful cleaning and disinfecting [wikipedia.org] properties. It's definitely the way to go.
Aspirate some today!
(Score: -1, Troll) by Anonymous Coward on Sunday June 07 2020, @02:03PM (2 children)
Don't get too fucking fancy with all your chemicals and la-de-dah else you might find some tear gas heading your way. In fact, that might be just what you need.
(Score: 4, Funny) by anubi on Sunday June 07 2020, @11:38PM (1 child)
I hope anyone reading these comments are at least somewhat technically literate.
This is a quite funny parody thread, as taking these advisories literally will have severe consequences.
If you popped into here from a search engine and are not technically literate, following the advice given here is about the worst thing anyone could do, and that is what makes them funny.
Now, take two aspirin in a glass of oxidane and call me in the morning.
"Prove all things; hold fast that which is good." [KJV: I Thessalonians 5:21]
(Score: 1, Funny) by Anonymous Coward on Monday June 08 2020, @12:50AM
Pipe down. Let the good Lord's work take its course.
It's for the good of us all.
In the long run.
(Score: 0) by Anonymous Coward on Sunday June 07 2020, @09:01PM
Better than syringes?
(Score: 2, Insightful) by Anonymous Coward on Sunday June 07 2020, @01:53PM (17 children)
Next steps, learn how to aim these "arrows". At present it sounds like this antibiotic is indiscriminate and will also kill all the desirable bacteria that we need--for example to digest food...
(Score: 3, Informative) by The Mighty Buzzard on Sunday June 07 2020, @02:02PM (4 children)
Plenty of antibiotics already do that. You get them back quickly enough after you've finished the course though. Faster if you don't go nuts with sanitizing everything.
My rights don't end where your fear begins.
(Score: 1, Insightful) by Anonymous Coward on Sunday June 07 2020, @04:53PM
Absolutely, and it's ridiculous that we still have doctors prescribing antibiotics without knowing what strain of bacteria that they're targeting or taking precautions to protect/replace the innocent bystanders that get killed in the process.
Bacteria are a huge part of our immune system as well as performing other helpful roles in and around the body. The medical community should show them far more respect as you're not realistically going to keep something completely free of bacteria.
(Score: 5, Interesting) by Azuma Hazuki on Sunday June 07 2020, @09:35PM (1 child)
It's not that easy. C. diff colonization and the resulting pseudomembranous colitis and dangerous diarrhea is a huge problem, and you don't get your gut flora back with just a couple of weeks of Chobani and oatmeal, or even probiotic supplements.
Not to mention, fluoroquinolones like ciprofloxacin (and anything with *flox* in it generally) have a bizarre laundry list of seemingly unrelated side effects--QTc prolongation and tendon rupture, for example--that make me wonder if there's collateral damage being done to mitochondria. Macrolides like azithromycin, which ostensibly work by binding to the 50S ribosomal subunit of bacteria, also have weird side effect profiles, as do their aminoglycoside cousins which bind to the 30S subunit.
And folate blockages remind me of drugs like methotrexate, usually used to treat cancer and rheumatoid arthritis. Just how selective are these new drugs regarding where they interfere with folate usage? If they're systemic and relatively indiscriminate, they border on chemotherapy with all that that implies.
I am "that girl" your mother warned you about...
(Score: 2) by takyon on Sunday June 07 2020, @09:47PM
They say it doesn't affect human cells... much:
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(Score: 2) by driverless on Monday June 08 2020, @06:36AM
That was my reaction to the article as well, it's easy enough to find some compound that kills everything it touches, but how well does it do at not killing everything but its target? That'll be the real acid test of the current silver bullet.
(Score: 3, Informative) by RS3 on Sunday June 07 2020, @03:54PM (10 children)
If someone is bad enough to need something this strong, patient is usually in hospital and antibiotic is usually delivered IV. It can still disrupt digestion and they'll give probiotics too. At least they should.
(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.
(Score: 4, Interesting) by hendrikboom on Sunday June 07 2020, @06:58PM
So eat yoghurt after your treatment. Or get a fecal transplant from someone as healthy as you aspire to be.
(Score: -1, Troll) by Anonymous Coward on Sunday June 07 2020, @03:55PM
Now we can get on with important things like what Kim Kardashian's wearing to Kanye's funeral.
(Score: -1, Troll) by Anonymous Coward on Sunday June 07 2020, @04:16PM
APK APK APK
(Score: 2) by PinkyGigglebrain on Sunday June 07 2020, @05:04PM
how fast will this compound break down once it it gets excreted and is released into the environment when, not if, it gets over used by cattle/food industry?
"Beware those who would deny you Knowledge, For in their hearts they dream themselves your Master."
(Score: 2, Interesting) by Anonymous Coward on Sunday June 07 2020, @09:01PM (4 children)
Used since forever, for exact same reason; it is less probable to evolve resistance when a bacterium needs to resist two different things at once to survive.
The way the resistance to this new compound will be evolved, is the same as with the multitude of single-target compounds before it; when some low concentrations of it get to be present in sewage, then in the wider environment, it will be unable to kill bacteria outright, but will do enough damage that those better able to resist it will have selective advantage. That way, the resistance will not need to appear at once in a 100% working form; better and better partial defences to either part of its dual effect will gradually evolve in parallel.
There is no silver bullet.
Still, money spent on doing research once again (high time after half a century of caching in evergreened patents) is MUCH better spent, than on marketers inventing new names for ancient stuff and on journalists rehashing fake prophecies of "DOOM!!!11"
(Score: 3, Interesting) by takyon on Sunday June 07 2020, @09:33PM (3 children)
I don't think it's impossible to find a "perfect" antibiotic. But it might end up being a nanomachine instead of a chemical.
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(Score: 0) by Anonymous Coward on Monday June 08 2020, @02:28AM (2 children)
So you want a "Maxwell's Demon" that can separate out and kill specific bacteria? That is a tall order indeed. Not even the tricorder could do that, weren't there infections that McCoy (et al) couldn't cure?
(Score: 0) by Anonymous Coward on Monday June 08 2020, @07:54AM
Nanoprobes did that on multiple instances. They even assimilate the hosts by targeting certain cells.
(Score: 2) by takyon on Monday June 08 2020, @06:29PM
Pick a different science fiction franchise and you can find a working version of the technology.
Nanobots are small, so maybe they can't fit enough storage or processing power to do anything meaningful by themselves. Instead, they could use sensors and wirelessly communicate to a central computer nearby. Scan a cell, send the data, ask for permission to target. Then hit bad cells with lasers or spikes. Repeat hundreds of billions of times. It could target bacteria, viruses, or cancer cells.
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