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New bacteria, and two potential antibiotics, discovered in soil

rockefeller.edu

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Re: New bacteria, and two potential antibiotics, discovered in soil

#21

Post by liquid_thyme »

w10-1 wrote: post #7

This should be re-titled something like: with 200x longer sequences and making products without culturing, dirt can make antibiotic gold. The two prospects: Erutacidin, disrupts bacterial membranes through an uncommon interaction with the lipid cardiolipin and is effective against even the most challenging drug-resistant bacteria. trigintamicin, acts on a protein-unfolding motor known as ClpX, a rare antibacterial ta…

Edit: nvm, brain fart. OP is correct.

> So being able to make the product without culturing the organism is key.

No, it isn't. The article talks about using chemical synthesis, rather than using a biological platform to express the product via genes.

"To convert the newly uncovered sequences into bioactive molecules, the team applied a synthetic bioinformatic natural products (synBNP) approach. They bioinformatically predicted the chemical structures of natural products directly from the genome data and then chemically synthesized them in the lab. With the synBNP approach, Brady and colleagues managed to turn the genetic blueprints from uncultured bacteria into actual molecules—including two potent antibiotics."

Re: New bacteria, and two potential antibiotics, discovered in soil

#23

Post by DaveZale »

pkaye wrote: post #18
DaveZale wrote: post #10

Look at the 1940s/1950s when some classic antibiotics were discovered. Pharma workers taking vacations overseas were asked to bring soil samples back to the lab. Great reading if you enjoy science history. https://asm.org/articles/2023/june/hunting-for-antibiotics-i...

Some of the immunosuppressant drugs were discovered from bacteria in soil including Tacrolimus and Sirolimus. And Cyclosporine and Mycophenolate came from a fungus in soil. I have a kidney transplant and use two of these medications daily.

Easter Island! Both of those.

Tacrolimus was discovered in 1987 by a Japanese team led by pharmacologist Tohru Kino; it was among the first macrolide immunosuppressants discovered, preceded by the discovery of rapamycin (sirolimus) on Rapa Nui (Easter Island) in 1975.[45] It is produced by a soil bacterium, Streptomyces tsukubensis.[46] The name tacrolimus is derived from "Tsukuba macrolide immunosuppressant".[47]

https://en.m.wikipedia.org/wiki/Tacrolimus

When you study organic synthesis, these kinds of structures are the Holy Grail. Sometimes it takes dozens of steps, and an overall yield of just a few percent to make them synthetically.

Re: New bacteria, and two potential antibiotics, discovered in soil

#24

Post by liquid_thyme »

kragen wrote: post #11

Newly discovered potential antibiotics are actually pretty common, and they would be critical to solving the antibiotic-resistance menace. But no major new families of antibiotics have been brought to market since about 01962, although a dozen or so families were discovered over the previous 20 years. (Or, maybe one new family was.) That was when drug regulation changed dramatically in the US with https://en.wikipedi…

>The problem was that it wasn't more effective than the existing standard of care; it was only equally effective.

That is misleading. When a clinical trial is designed for non-inferiority, it doesn't say anything about being superior or equal. Just as legally, a defendant is either guilty or not guilty - there is no legal adjudication of being "innocent".

These drugs are not comparable (different stability profiles, different mechanisms of action, etc) and to say they're equal is highly misleading.

>and the absence of the drugs that would have been discovered since then has surely killed many more people than the inadvertent use of harmful drugs ever could have.

There is no evidence that safety regulations have denied us some miracle drug. I don't want the FDA approving drug products that are harmful to the general population. You haven't made a good argument for "the greater good" besides a reference to magainin, a product for topical treatment of foot ulcers. There are thousands of known anti microbial peptides.

https://pmc.ncbi.nlm.nih.gov/articles/PMC7937881/

Re: New bacteria, and two potential antibiotics, discovered in soil

#25

Post by philipkglass »

liquid_thyme wrote: post #21
w10-1 wrote: post #7

This should be re-titled something like: with 200x longer sequences and making products without culturing, dirt can make antibiotic gold. The two prospects: Erutacidin, disrupts bacterial membranes through an uncommon interaction with the lipid cardiolipin and is effective against even the most challenging drug-resistant bacteria. trigintamicin, acts on a protein-unfolding motor known as ClpX, a rare antibacterial ta…

Edit: nvm, brain fart. OP is correct. > So being able to make the product without culturing the organism is key. No, it isn't. The article talks about using chemical synthesis, rather than using a biological platform to express the product via genes. "To convert the newly uncovered sequences into bioactive molecules, the team applied a synthetic bioinformatic natural products (synBNP) approach. They bioinformatically…

Isn't that saying the same thing a different way? Chemical synthesis is a way to make the assumed molecular product without culturing the organism.

Re: New bacteria, and two potential antibiotics, discovered in soil

#26

Post by kragen »

liquid_thyme wrote: post #24
kragen wrote: post #11

Newly discovered potential antibiotics are actually pretty common, and they would be critical to solving the antibiotic-resistance menace. But no major new families of antibiotics have been brought to market since about 01962, although a dozen or so families were discovered over the previous 20 years. (Or, maybe one new family was.) That was when drug regulation changed dramatically in the US with https://en.wikipedi…

>The problem was that it wasn't more effective than the existing standard of care; it was only equally effective. That is misleading. When a clinical trial is designed for non-inferiority, it doesn't say anything about being superior or equal. Just as legally, a defendant is either guilty or not guilty - there is no legal adjudication of being "innocent". These drugs are not comparable (different stability profiles,…

"There is no evidence that safety regulations have denied us some miracle drug."

Well, of course we don't know of a specific miracle drug they've denied us, because it isn't until after a drug is in wide use that you find out whether it's a miracle drug or not. But we can see that there were enormous numbers of miracle drugs in the 20 years immediately preceding the safety regulations, and almost none in the 63 years since then. There have definitely been some† but a very large slowdown is clearly evident if you look at the history. Most of even the important new drugs since then are slight variations on previously known molecules.

A reasonable inference from these observations is that safety regulations have denied us a lot of miracle drugs.

______

† zidovudine, Paxlovid, oral rehydration therapy, ivermectin, propofol, SSRIs, sildenafil, acyclovir, misoprostol, ritonavir, and arguably buprenorphine come to mind; and time will tell whether lovastatin and semaglutide belong on this list or on the failures list with fen/phen and heroin.

Re: New bacteria, and two potential antibiotics, discovered in soil

#27

Post by kragen »

ipaddr wrote: post #17
fgfarben wrote: post #13

Earlier quoted context omitted.

My pet idea is that Western societies should prescribe antibiotics at random to a different tiny fraction of the elderly population each month / year. People who suffer from unexplained / untreatable diseases like arthritis or MS might get some relief, while there would be an added pressure on the pharma industry to innovate in antibiotic development by accelerating the loss of existing antibiotic efficacy through th…

Horrible idea antibiotics are not toys and have side effects. Don't use elderly people for experiments when they are the one group least able to handle this. You want to cause current antibiotics to be less useful so pharma will invest more? Just allow generic versions. If you want to pressure the pharma industry use laws.

Every major family of antibiotics has generic versions, and that is not resulting in the needed discovery. This is probably because the vast majority of the "investment" required is in compliance with regulations that didn't exist when the currently-widely-used antibiotics were discovered.

Some antibiotics do have a good enough safety profile that such occasional speculative use would be a good tradeoff. Elderly people are also the one group least able to handle infections! Others do not.

Re: New bacteria, and two potential antibiotics, discovered in soil

#28

Post by liquid_thyme »

kragen wrote: post #26
liquid_thyme wrote: post #24

Earlier quoted context omitted.

>The problem was that it wasn't more effective than the existing standard of care; it was only equally effective. That is misleading. When a clinical trial is designed for non-inferiority, it doesn't say anything about being superior or equal. Just as legally, a defendant is either guilty or not guilty - there is no legal adjudication of being "innocent". These drugs are not comparable (different stability profiles,…

" There is no evidence that safety regulations have denied us some miracle drug. " Well, of course we don't know of a specific miracle drug they've denied us, because it isn't until after a drug is in wide use that you find out whether it's a miracle drug or not. But we can see that there were enormous numbers of miracle drugs in the 20 years immediately preceding the safety regulations, and almost none in the 63 yea…

In the domain of natural sciences, throughout history, there have been periods of high and low rate of progress. All you have evidence for is that progress has slowed down and your own personal belief linking it to another event in history (among thousands of events) - But you haven't shown any positive evidence of something being lost (i.e. scientific data/research), besides arguing for it with words. Sorry, your so called reasonable inference doesn't seem reasonable to me.

Re: New bacteria, and two potential antibiotics, discovered in soil

#29

Post by liquid_thyme »

philipkglass wrote: post #25
liquid_thyme wrote: post #21

Earlier quoted context omitted.

Edit: nvm, brain fart. OP is correct. > So being able to make the product without culturing the organism is key. No, it isn't. The article talks about using chemical synthesis, rather than using a biological platform to express the product via genes. "To convert the newly uncovered sequences into bioactive molecules, the team applied a synthetic bioinformatic natural products (synBNP) approach. They bioinformatically…

Isn't that saying the same thing a different way? Chemical synthesis is a way to make the assumed molecular product without culturing the organism.

You're correct, I'm wrong!

Re: New bacteria, and two potential antibiotics, discovered in soil

#30

Post by akoboldfrying »

fgfarben wrote: post #13
kragen wrote: post #11

Newly discovered potential antibiotics are actually pretty common, and they would be critical to solving the antibiotic-resistance menace. But no major new families of antibiotics have been brought to market since about 01962, although a dozen or so families were discovered over the previous 20 years. (Or, maybe one new family was.) That was when drug regulation changed dramatically in the US with https://en.wikipedi…

My pet idea is that Western societies should prescribe antibiotics at random to a different tiny fraction of the elderly population each month / year. People who suffer from unexplained / untreatable diseases like arthritis or MS might get some relief, while there would be an added pressure on the pharma industry to innovate in antibiotic development by accelerating the loss of existing antibiotic efficacy through th…

> there would be an added pressure on the pharma industry to innovate in antibiotic development by accelerating the loss of existing antibiotic efficacy through the evolution of resistance

You're joking, right?

Total antibiotic resistance is what we're trying to minimise, remember. You're proposing to achieve that in the long term by making it worse in the short term, but the only way that makes sense is if there is actually an abundance of new antibiotics "out there" waiting to be discovered, and the binding constraint currently limiting their development is that pharmaceutical companies can't be bothered researching them. But that is obviously not true -- steadily growing resistance has raised alarm for decades, and any pharma company that could produce a genuinely new antibiotic today would make immediate bank.

IOW, the incentives are already there and they aren't helping, so why take the extra step of making things deliberately worse?

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