[HN Gopher] New bacteria, and two potential antibiotics, discove...
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New bacteria, and two potential antibiotics, discovered in soil
Author : PaulHoule
Score : 103 points
Date : 2025-09-24 16:03 UTC (6 hours ago)
(HTM) web link (www.rockefeller.edu)
(TXT) w3m dump (www.rockefeller.edu)
| rogerrogerr wrote:
| > hundreds of complete bacterial genomes never seen before
|
| Welllll that doesn't sound like a great idea
| PaulHoule wrote:
| Just because you don't know they are there doesn't mean they
| aren't there!
| kulahan wrote:
| Meh, they came from the soil. It's always been here, just never
| seen by human eyes. That's true of lots and lots of bacteria
| though - we find new species pretty much every single time we
| take a stomach sample from someone, let alone random forest
| soil.
| PaulHoule wrote:
| Many bacteria have commensal lifestyles --- scientists don't
| feel in control if they can't culture bacteria in isolation
| but in nature many bacteria aren't metabolically complete and
| son's live in isolation.
| choilive wrote:
| There are millions on the lower bound of bacteria species we
| havn't identified, trillions on the upper bound. Unknown
| bacteria are literally everywhere, but the simple act of
| finding and sequencing them is nothing to be afraid of.
| throwup238 wrote:
| Also known as biological dark matter:
| https://en.m.wikipedia.org/wiki/Biological_dark_matter
| throwawaysoxjje wrote:
| Sounds normal, most bacteria can't be cultured. Only about 50%
| of the ones in your mouth can be
| w10-1 wrote:
| 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 target
|
| The difficulty with bacterial DNA is that they have common
| elements and actively share DNA to boot. Sequencing only short
| sections make genome assembly unreliable. 200x longer sequences
| makes much more accurate genomes.
|
| Then even if you find genes, we can't usually culture enough
| bacteria to make the product (typically instead injecting the
| sequences into bacteria we can culture). So being able to make
| the product without culturing the organism is key.
| dillydogg wrote:
| Spoiler, I haven't read the article, but my understanding is
| cardiolipin targeting antibiotics have failed in the past
| because our mitochondria are enriched for it. (Which makes
| sense here because the mitochondria are derived from ancient
| bacteria). I'm sure there is potential for optimization for
| medical applications, but we will have to be very careful for
| adverse effects.
| liquid_thyme wrote:
| 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."
| philipkglass wrote:
| 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.
| liquid_thyme wrote:
| You're correct, I'm wrong!
| DaveZale wrote:
| 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...
| pkaye wrote:
| 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.
| DaveZale wrote:
| 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.
| kragen wrote:
| 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.wikipedia.org/wiki/Kefauver%E2%80%93Harris_Amendm...,
| for example requiring clinical trials to provide evidence that
| drugs were effective, rather than just safe. It's also when they
| started outlawing recreational drugs; the Single Convention on
| Narcotic Drugs wasn't until 01961, and it didn't cover
| amphetamines, downers, or psychedelics.
|
| Because so much of 20th-century drug research happened in the US
| (because the US had capitalism) the clinical-trials requirement
| and the Drug War there had an outsized effect, and other
| countries copied them afterwards.
|
| One particular case that I studied was Zasloff's "magainin":
| https://en.wikipedia.org/wiki/Magainin which was denied licensing
| even though the clinical trials found that it was both safe and
| effective. The problem was that it wasn't _more_ effective than
| the existing standard of care; it was only _equally_ effective.
|
| It seems certain that the Kefauver-Harris Drug Act has prevented
| innumerable cases of useless or harmful drugs from being
| marketed. But, looking at the history of drug development, it
| also seems clear that the rapid drug development in the decades
| up to 01962 virtually halted at that time, 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.
| fgfarben wrote:
| 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 the evolution of resistance.
| kragen wrote:
| It's a promising idea, but probably wouldn't help with drug
| discovery.
| ipaddr wrote:
| 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.
| kragen wrote:
| 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.
| liquid_thyme wrote:
| >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/
| kragen wrote:
| " _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, arguably buprenorphine, sildenafil,
| acyclovir, misoprostol, and ritonavir come to mind; and time
| will tell whether lovastatin and semaglutide belong on this
| list or with fen/phen and heroin.
| liquid_thyme wrote:
| 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.
| pfdietz wrote:
| The paper:
|
| https://www.nature.com/articles/s41587-025-02810-w
|
| One of the antibiotics targets a protein that is also essential
| in mitochondria, so it's not a good candidate for a drug. The
| other targets bacterial cell membranes and showed no resistance
| developing, which seems more promising.
| kjkjadksj wrote:
| There is so much potential in sampling soil. Spinosad was found
| like this as well only a few decades ago.
| mrbonner wrote:
| Turns out the old saying, "Let the kids play and eat dirt,"
| might've been right all along--who knew? All this time, they
| might've been giving themselves tiny doses of natural
| antibacterials without even realizing it.
| ChuckMcM wrote:
| Is there a good explainer of the challenges of growing dirt based
| bacteria in the lab?
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