Resistance is futile?

January 7, 2015 1:51 PM

For the first time in nearly thirty years, a new class of antibiotics may be on the way — and the good news doesn't end there.

A new study published in Nature details how the new antibiotic, teixobactin, was isolated using a novel technique. Most antibiotics come from antimicrobial compounds produced naturally by soil bacteria, but only about 1% of soil bacteria have previously been cultivable in the laboratory. The Nature researchers believe that the new technique, called iChip, will allow the cultivation of up to 50% of soil bacteria, dramatically expanding possibilities for the development of more antibiotics to come.

Teixobactin itself appears to be highly effective against Gram-positive bacteria, including Mycobacterium tuberculosis, which causes TB, and MRSA (methicillin-resistant Staphylococcus aureus), a problematic multi-drug-resistant strain of the skin-dwelling bacterium S. aureus that spreads in health-care facilities. The drug was shown to be non-toxic to mice, though human clinical trials are unlikely to start for a couple more years. However, hope abounds that even if teixobactin ultimately fails as a human drug, iChip may still end up as a breakthrough in the war against antimicrobial resistance.

posted by saturday_morning (51 comments total)

Awesome!
posted by Slinga at 1:57 PM on January 7, 2015 [1 favorite]

!
posted by Jacqueline at 1:57 PM on January 7, 2015

Anything new that works against MRSA would be a great gift.
posted by tavella at 1:58 PM on January 7, 2015 [5 favorites]

Hmmmm. this article is full of a lot of hopeful language, i hope it's not another 'fusion is just ten years away' kind of thing.
I deal with ab resistance all the time, and it's worrying to say the least. seldom life-threatening in my field, but the amount of non-compliance from patients coupled with poor prescribing discipline from providers is only making things worse faster.
posted by OHenryPacey at 1:58 PM on January 7, 2015 [5 favorites]

Anybody got any numbers on what a MRSA-killer would do to iatrogenic fatalities?
posted by Pope Guilty at 2:07 PM on January 7, 2015

BBC News article. The detail I like is that 25 brand new antibiotic agents (including teixobactin) were all discovered in a researcher's back yard.
posted by rongorongo at 2:10 PM on January 7, 2015 [2 favorites]

The researchers also believe that bacteria are unlikely to develop resistance to teixobactin.

It targets fats which are essential for building the bacterial cell wall, and the scientists argue it would be difficult to evolve resistance.

"Here is an antibiotic that essentially evolved to be free of resistance," said Prof Lewis. "We haven't seen that before."

So they believe that bacteria aren't capable of evolving to counter this new drug that other bacteria unexpectedly evolved to produce. I'm sure that's going to work out great.
posted by neckro23 at 2:10 PM on January 7, 2015 [13 favorites]

So does this buy us another 40 years until we get bacteria resistant to this new drug?
posted by JauntyFedora at 2:11 PM on January 7, 2015 [2 favorites]

I have developed sensitivity to several classes of antibiotic, so it's encouraging on a personal level. Antibiotic resistance is a huge issue.
posted by theora55 at 2:11 PM on January 7, 2015 [1 favorite]

Most antibiotics come from antimicrobial compounds produced naturally by soil bacteria

That is fascinating all by itself and I would love to learn more about it.
posted by Joey Buttafoucault at 2:14 PM on January 7, 2015 [6 favorites]

I know that AB resistance has become a huge problem in some countries where people can get antibiotics over the counter, and use them for pretty much any ailment that they get.

This would be a huge deal, so ::fingers crossed::
posted by quin at 2:19 PM on January 7, 2015

What's really important, though, is how the hell do you pronounce it? Like the Portuguese name Teixeira?

Cue Daily Show montage of news anchors, each pronouncing it a different way.
posted by XMLicious at 2:22 PM on January 7, 2015 [3 favorites]

I think the hope is that resistance will be a little slower in coming because the target isn't a protein, it's a conserved chemical component of the (gram-positive) cell wall, and because the bacteria that make it are gram negative they don't have to be resistant to it themselves, so it's not a matter of just scavenging some bits of DNA from neighboring bacteria to pick up resistance. An easier route to resistance, though, might be degrading teixobactin itself, or getting it out of the cell with a repurposed efflux pump.

(Gram-positive vs. -negative is a rough division among types of bacteria that is super empirical - some bacteria get stained with this dye and those are the positives, while others don't and they're called the negatives. It turns out this mostly corresponds to structural differences - i.e., whether the bacterium has a single lipid membrane and a thick cell wall like Staph aureus, or a double lipid membrane with a thin cell wall in the middle like E. coli. Teichoic acid is a component of Gram-positive cell walls but, I guess, not of Gram-negative cell walls.)

They've already demonstrated that it works in mice, so that already separates it from a "fusion is ten years away" thing. The main barrier of course is human clinical trials, where the vast majority of drugs fail; but even if it were moderately toxic, it's still better than sepsis from a vancomycin-resistant infection, so the FDA might be lenient (I wonder if it counts as an orphan disease?).

Soil bacteria are crazy diverse and seem to do some very interesting metabolism (some are not only resistant to common existing antibiotics but appear to actually eat them for energy; others do things like degrade rotting wood fibers and produce things like butanol). I'm guessing we're going to see a lot come out of this general area over the next couple of decades.
posted by en forme de poire at 2:23 PM on January 7, 2015 [43 favorites]

Oops, the target is actually a precursor of teichoic acid. (My guess is that this is what the name "teixobactin" refers to - the "ch" is a chi in the original Greek root - so it's probably pronounced with a "k" sound. Could be wrong though.)
posted by en forme de poire at 2:26 PM on January 7, 2015 [1 favorite]

Yay! Just in time! Load 'em up in the tank and plug the spigot into the cows!
posted by Artw at 2:27 PM on January 7, 2015 [3 favorites]

Soil bacteria are crazy diverse and seem to do some very interesting metabolism (some are not only resistant to common existing antibiotics but appear to actually eat them for energy; others do things like degrade rotting wood fibers and produce things like butanol). I'm guessing we're going to see a lot come out of this general area over the next couple of decades.

Yes! As a soil & ecology nerd, this article really buried the lede - being able to culture 50% of soil bacteria (we're currently around 1%) would be absolutely incredible regardless of whether we found new antibiotics or not. It sure demonstrates the argument for preserving biodiversity, though; none of these developments would be possible if we'd caused these species to go extinct or if there wasn't such incredible biodiversity present in soil communities.

Development of new drugs and new technologies is an oft-overlooked value of biodiversity, and I hope these developments help to cement that idea so that we can stop arguing about whether biodiversity is a true ecosystem service worth preserving.
posted by dialetheia at 2:31 PM on January 7, 2015 [34 favorites]

I've often worried about living in the brief period of time where we had antibiotics to the diseases that could kill us, as the ever-evolving nature of MRSA seemed to indicate we were nearing the end of a golden age. Though developing Fantastic Voyage technology would also work.
posted by fifteen schnitzengruben is my limit at 2:33 PM on January 7, 2015

This is fascinating - thanks for the post, and also thanks en forme de poire for the further explanation.
posted by une_heure_pleine at 2:35 PM on January 7, 2015 [2 favorites]

This is brilliant news, thanks for the great post and comments!

*does a tiny "maybe we're not all doomed" dance*
posted by metaBugs at 2:39 PM on January 7, 2015 [3 favorites]

What's really important, though, is how the hell do you pronounce it? Like the Portuguese name Teixeira?

My policy is: when in doubt, pronounce "x" as an alveolar lateral click like in Xhosa. Livens things up.
posted by nebulawindphone at 2:43 PM on January 7, 2015 [15 favorites]

This is great news! Also, hug a research scientist today. They are heroes in the truest sense of the word.
posted by Klaxon Aoooogah at 2:43 PM on January 7, 2015 [5 favorites]

Maybe we'll find some shadow biosphere antibiotic microbes with superpowers, which under the light of a yellow sun can leap any Earthly cell wall in a single bound.
posted by XMLicious at 2:49 PM on January 7, 2015

"Resistance is inevitable."
- Mark Crislip Previously

"Life finds a way."
- Dr Ian Malcolm Previously
posted by wotsac at 2:56 PM on January 7, 2015 [2 favorites]

Oh my goodness this is tremendously exciting news. I'm not sure whether to be more excited about the MRSA part of the TB part or the 50% part.

My policy is: when in doubt, pronounce "x" as an alveolar lateral click like in Xhosa. Livens things up.

On a completely unrelated note, I had to sing a piece in Zulu once, which includes that click. I'm Western-classical-trained. That was a hell of a journey.
posted by KathrynT at 3:04 PM on January 7, 2015 [4 favorites]

Anybody got any numbers on what a MRSA-killer would do to iatrogenic fatalities?

Rough numbers, but looks like ~80% of MRSA is hospital-acquired and MRSA kills ~19,000 per year in the USA. However, Staph aureus itself is a pretty nasty bug whether or not it's resistant. Methicillin resistance increases the likelihood of death from S. aureus infection by "only" about ~50%.
posted by saturday_morning at 3:05 PM on January 7, 2015

Growing Unculturable Bacteria. The ichip stuff is discussed near the end. I'd love to see a simplified explanation...
posted by gray17 at 3:14 PM on January 7, 2015

Antibiotics are one of those areas where traditional market forces break down. Because of the well-known problems of drug resistance, a new, powerful, first-in-class antibiotic is likely to be used sparingly by doctors—held as a drug of last resort. So perversely, a really effective new antibiotic is not likely to generate much profit, which is bad news for the pharmaceutical company that plowed a billion dollars into developing it. That's one reason why so few antibiotics have been developed over the last few decades.

Unfortunately, new discoveries like this aren't likely to change that, because most of the the cost of drug development comes from running clinical trials, as opposed to preclinical stuff like target identification and lead optimization.
posted by dephlogisticated at 3:17 PM on January 7, 2015 [6 favorites]

Now our Cattle will be stronger that ever!!!!
posted by asra at 3:19 PM on January 7, 2015 [4 favorites]

Another bit of bad news: the article states that the new compound is similar to vancomycin, which makes it very likely that the drug will be IV only.
posted by dephlogisticated at 3:20 PM on January 7, 2015

...the article states that the new compound is similar to vancomycin, which makes it very likely that the drug will be IV only.
- dephlogisticated

No, that's GOOD. Harder to use in unsupervised or industrial (animal husbandry) settings, so a longer opportunity to use before large-scale resistance develops.
posted by Dreidl at 3:26 PM on January 7, 2015 [23 favorites]

Antibiotics are one of those areas where traditional market forces break down. Because of the well-known problems of drug resistance, a new, powerful, first-in-class antibiotic is likely to be used sparingly by doctors—held as a drug of last resort. So perversely, a really effective new antibiotic is not likely to generate much profit, which is bad news for the pharmaceutical company that plowed a billion dollars into developing it. That's one reason why so few antibiotics have been developed over the last few decades.

I don't mean to be too pedantic or nit-picky, but this is actually an example of market forces working entirely correctly. The problem is that the market is completely amoral and has no formal or substantive tendency to promote the general welfare of society, which makes it very irrational and even perverse to rely upon its mechanics for innovation in health care.
posted by clockzero at 3:28 PM on January 7, 2015 [11 favorites]

No, that's GOOD. Harder to use in unsupervised or industrial (animal husbandry) settings, so a longer opportunity to use before large-scale resistance develops.

I see your point, but there are associated downsides that go beyond simple inconvenience. A big glycopeptide like vancomycin can't penetrate into many tissues because of its high lipophilicity, and requires very careful dosing/monitoring to prevent nephrotoxicity and other major side effects. In other words, it's not ideal from a clinical standpoint. Though teixobactin doesn't look to be quite as big or ugly as the glycopeptide antibiotics, so perhaps its properties will be somewhat different.
posted by dephlogisticated at 3:46 PM on January 7, 2015 [4 favorites]

If anyone's curious for a primer on the various existing classes of antibiotics and how they work, have a look in here. I meant to link it in the original post but somehow it got dropped, oopsie.
posted by saturday_morning at 3:48 PM on January 7, 2015 [2 favorites]

Okay, to clear some of these things up, this hasn't even been phase one yet. 1 in 5000 drugs make it through clinical trials. Secondly, if it is not available for oral absorption (like vancomycin) it can be abused in cattle because they don't want the drug absorbed after oral administration.
Third, resistance develops fast. Every drug that is commonly used for five to ten years will start to show resistance among some bacteria. (Although like Penicillin and syphilis, not complete resistance by all organisms).
And there have been new antimicrobial categories in the last thirty years. (They say antibiotic, if they are strictly speaking of one organism producing an antiobiotic compound against another, yes there have been new ones. If they are speaking of antimicrobials then there have been a lot more - integrase inhibitors among many examples).
posted by dances_with_sneetches at 3:51 PM on January 7, 2015 [1 favorite]

rongorongo: "The detail I like is that 25 brand new antibiotic agents (including teixobactin) were all discovered in a researcher's back yard."

Fun Peoria Fact #142: The USDA lab in Peoria was tasked with coming up with a fast-growing strain of penicillin during World War II (because it took so long to grow a dose of antibiotics that its use was severely restricted), to make it a viable medical and commercial product. Scientists sent in penicillin strains and soil samples from all over the world that failed and failed to grow at scale; the winning strain of penicillin, which kicked off the antibiotics revolution by making mass production of the drug possible, was found right here in Peoria, in 1943, on a moldy supermarket cantaloupe, by a lab worker named Mary Hunt.
posted by Eyebrows McGee at 3:53 PM on January 7, 2015 [39 favorites]

I deal with ab resistance all the time, and it's worrying to say the least. seldom life-threatening in my field, but the amount of non-compliance from patients coupled with poor prescribing discipline from providers is only making things worse faster.

This is only anecdotal, but in the last 2 or 3 years the GPs I've seen have been much less likely to prescribe antibiotics at all. I am prone to sinus infections in the winter months, and while in years past I would get a prescription for antibiotics, at this point every time I go to the doctor when I feel one starting they tell me to take hot showers often, use a saline nasal spray, and come back if things aren't getting better in a week's time because it could simply be a virus. And frankly they've been right, it has been going away, even though it's generally a painful few days. So that's encouraging.
posted by Hoopo at 4:01 PM on January 7, 2015 [3 favorites]

Wonderful news... I have a relative fighting two different hospital acquired drug resistant infections as we speak, which is how I know that Vancomycin is no longer IV only but also available PO.
posted by spitbull at 4:05 PM on January 7, 2015 [1 favorite]

The researchers also believe that bacteria are unlikely to develop resistance to teixobactin.


Rocky: "But that trick never works."
Bullwinkle: "This time for sure!"
posted by Cosine at 4:06 PM on January 7, 2015 [4 favorites]

Wonderful news... I have a relative fighting two different hospital acquired drug resistant infections as we speak, which is how I know that Vancomycin is no longer IV only but also available PO.

Vancomycin isn't absorbed through the GI tract, but it can be used orally for intestinal infections such as C. difficile, which itself is often caused by antibiotic treatment.
posted by dephlogisticated at 4:12 PM on January 7, 2015 [1 favorite]

Anything to battle MRSA is a damn good thing in my book. Because fuck MRSA.
posted by PROD_TPSL at 4:20 PM on January 7, 2015 [3 favorites]

rongorongo: "The detail I like is that 25 brand new antibiotic agents (including teixobactin) were all discovered in a researcher's back yard."

From Bill Bryson's A Short History of Nearly Everything:

In the 1980s, a pair of Norwegian scientists, Jostein Goksøyr and Vigdis Torsvik, collected a gram of random soil from a beech forest near their lab in Bergen and carefully analyzed its bacterial content. They found that this single small sample contained between 4,000 and 5,000 separate bacterial species, more than in the whole of Bergey’s Manual. They then traveled to a coastal location a few miles away, scooped up another gram of earth, and found that it contained 4,000 to 5,000 other species.

The mind boggles at the possibilities.
posted by Mitheral at 4:37 PM on January 7, 2015 [2 favorites]

Since the style of beer in a region depended largely on the water hardness and the kinds of yeast that were floating around, different locations created different styles (why there are stouts in one location or pilsners in another, for example, or why neutral water is great for doing all kinds of things).

Extending that outward, what are the soil requirements are for developing really good antibiotic agents from the local fauna?
posted by fifteen schnitzengruben is my limit at 4:54 PM on January 7, 2015 [1 favorite]

Klaxon Aoooogah : hug a research scientist today.

Or call your congress-critter to ask for more funding for the NSF and NIH?
Or hire an ex-scientists who quite academia for myriad reasons? etc.
posted by jeffburdges at 6:32 PM on January 7, 2015 [1 favorite]

This reddit comment explains how the soil bacteria was cultured.
posted by ryanrs at 9:41 PM on January 7, 2015 [10 favorites]

So far 2015 looks better than 2014.
posted by Gymnopedist at 9:53 PM on January 7, 2015 [1 favorite]

Antibiotic Failure Will Kill 10 Million People a Year by 2050
posted by homunculus at 9:56 PM on January 7, 2015

Yay! As a colonized healthcare worker, I hail our new freedom fighters!
posted by eggkeeper at 9:15 AM on January 8, 2015 [1 favorite]

(Throws out half-finished manuscript of sci-fi novel where we have FTL but 20-year-olds regularly die of drug-resistant TB)
posted by thecaddy at 11:47 AM on January 8, 2015

The Drug War - we're doing it wrong.

We should be putting antibiotics on the Schedule, and not recreational drugs. The misuse of antibiotics harms literally everyone, while recreational drugs, when they're harmful at all, only harm the individual. The vast majority of harms associated with recreational drugs result from prohibition, rather than the drug itself. And, by restricting antibiotics, the drug cops would still have something to do after recreational drug prohibition ended, (and be able to feel good about their work). Perhaps under this scenario, law enforcement would be less resistant to repeal?
posted by sudon't at 12:01 PM on January 8, 2015 [4 favorites]

MRSA kills ~19,000 per year in the USA

Good healthcare practices seem to have got that down from 21,138 in 2005 to 11,285 in 2011, which seems like a very good thing. As a 3-time inpatient in the UK, in 1992, 2002 and 2012, I can say that there have been step changes in cleanliness and screening over that period. (Although my awareness was increased somewhat by the fact that I was working in healthcare by the time I got that third hospitalisation. Even as a keyboard jockey working on a site with no patients, I have to be up to date on infection control.)

The counterpart of life always finding a way is that intelligent macro-organisms can do pretty smart work to make sure that the bacteria are on the back foot, and the reduction in healthcare acquired infections across the developed world since the beginning of the 21st century is a cause for optimism that perhaps infection will only be as much of an adversary in the future as it was in the second half of the 21st century.
posted by ambrosen at 1:39 PM on January 8, 2015 [1 favorite]

Let's hope we can get these into production within the next decade.
and pray that a pandemic doesn't get us in the interim
posted by BlueHorse at 10:36 PM on January 8, 2015