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.
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.
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.
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.
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.
I'm going to guess that a lot of soil bacteria exist in complex ecological networks, aka depend on the presence of other microbes (or at least their byproducts), which runs counter to our obsession (with good reason) with getting pure cultures when culturing them. The secondary metabolites and various factors produced by bacteria are extremely diverse, and it's a lot of work to try to try every combination.
Turns out that growing infectious bacteria is a usually easier since they often grow in rich/meat broths at body temperatures.
A few years ago a group at Northeastern developed a device that allows single bacteria/colonies to be isolated while still in indirect contact with the soil.
Now, it'd be nice to keep those for as long as possible. Is regulation on the use of these feasible? I'd think that if your law just restricts its use on animals (which I believe is where the majority of antibiotic-resistance comes from) that would be easier to pass than if you tried to restrict its use on humans, but I don't know if there's precedent for it.
Looking forward for a new break-through.
Will they find another Nobel-prize winning medicine? Like the very cheap Ivermectin that saved so many people from blindness (and various other diseases).
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[ 0.30 ms ] story [ 34.1 ms ] threadWelllll that doesn’t sound like a great idea
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.
https://asm.org/articles/2023/june/hunting-for-antibiotics-i...
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.
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.
Turns out that growing infectious bacteria is a usually easier since they often grow in rich/meat broths at body temperatures.
A few years ago a group at Northeastern developed a device that allows single bacteria/colonies to be isolated while still in indirect contact with the soil.
https://en.wikipedia.org/wiki/Isolation_chip
In situ cultivation of previously uncultivable microorganisms using the ichip https://www.nature.com/articles/nprot.2017.074 https://sci-hub.ru/10.1038/nprot.2017.074
Looks like they patented it, not sure if others are working on similar things.
To better answer your question, the inventor of the device has his own theories as to why this happens (although I like my idea better)..
The phenomenon of microbial uncultivability https://www.sciencedirect.com/science/article/abs/pii/S13695...
Now, it'd be nice to keep those for as long as possible. Is regulation on the use of these feasible? I'd think that if your law just restricts its use on animals (which I believe is where the majority of antibiotic-resistance comes from) that would be easier to pass than if you tried to restrict its use on humans, but I don't know if there's precedent for it.