Antibiotic Breakthrough Ends 25-Year Discovery Drought
bloomberg.com
bloomberg.com
"...strikes multiple targets, including cell walls...Since the lipid structures it attacks don’t evolve as quickly as frequently mutating proteins, it may take the bacteria longer than usual to develop a survival tactic."
Proteins change often and quickly, but basic cell structures may take longer or never adapt.
But I'm not a pathobiologist, I just play one on the Internet
Given that this was discovered from existing bacteria, there's a significant chance nature has already done the first and last of those. The middle mechanism is likely possible for any bacteria, if you have enough to start with (there's nothing I could find with Google in a minute to describe teixobactin's transport mechanism).
In general there was a rule of thumb when I was doing microbiology of this exact nature (an antibiotic created by some strains of E. Coli), if you exposed a million bacteria cells to a generic antibiotic, 1 would would survive due to a mutation (a useful number in microbiology, likely dead meat in the body). Streptomycin was more effective, 1 in a billion.
ADDED: it's implied by the Nature abstract that the researchers have tried this general approach, that they were not able to find spontaneous resistance mutations in a couple of the standard nasties. But extending on the above thesis, ecologically, there's a respectable chance some bacteria out there have developed defenses. It's a jungle out there, and e.g. in your gut, that's why fungi and bacteria developed antibiotics in the first place. They aren't expending resources just to allow us to kill the inconvenient ones.
Edit: deleted incorrect information about b-lactamase.
Nature asked me for $$$ to read the article, so ... from your description, that's leaving out the hard, fast test of just culturing several billion of those, adding a lethal concentration and seeing if there are any survivors. Which is how I gather one found spontaneous transport mutations, at least circa 1977. The state of the art has likely improved, and these guys used novel microbiological methods to find the bacteria that produce teixobactin in the first place.
ADDED: thanks to betatim's link to the full text, I've skimmed it and read the discussion, and teixobactin sound quite promising. They haven't found any protein to which it binds, and they think it binds to an "Achilles's heel" in the outer cell wall. The method described to generate resistance was their most extreme attempt, so I assume they tried the fast way, and I can see why it didn't work.
Ecologically, they believe there's little gene (e.g. plasmid) transfer between these soil bacteria and human pathogens, and the "30 year" bit came from experience with vancomycin, to which it has a lot of similarity. And they've done lots of tests for human toxicity and effectiveness in mammals. It's still early in the process, but a degree of fuss is warranted, especially due to their discovery method.
>We were unable to obtain mutants of S. aureus or M. tuberculosis resistant to teixobactin even when plating on media with a low dose (4 X MIC [minimal inhibitory concentration]) of the compound. Serial passage of S.aureus in the presence of sub-MIC levels of teixobactin over a period of 27 days failed to produce resistant mutants as well (Fig. 2d, Supplementary Discussion)
From the Supplementary information:
>Cells were added to teixobactin present at 0.25xMIC, 0.5xMIC,1xMIC,2xMIC and 224xMIC. At 24 hour intervals, the cultures were checked for growth. Cultures from the second highest concentrations that allowed growth (OD600≥2) were diluted 1:100 into fresh media containing 0.25xMIC, 0.5xMIC,1xMIC,2xMIC and 4xMIC of teixobactin. This serial passaging was repeated daily for 30 days. Any cultures that grew at higher than the MIC levels were passaged on drug free MHA plates and the MIC was then determined by broth microdilution. No resistant mutants were obtained. This experiment was repeated, and produced the same negative result. In order to maximize the chance of obtaining a resistant mutant, we performed an additional experiment with very small incremental increases in the drug concentration. Cells were added to a series of tubes with small differences in the concentration of teixobactin (0.06xMIC, 0.25xMIC, 0.5xMIC, 0.75xMIC,1xMIC, 1.25xMIC, 1.5xMIC, and 2xMIC). At 24 hour intervals, cultures from the highest concentration that allowed growth to a minimum OD600 of 0.2 were diluted 1:100 into fresh medium containing 0.06xMIC, 0.25xMIC, 0.5xMIC, 0.75xMIC,351xMIC, 1.25xMIC, 1.5xMIC, and 2xMIC. This passaging was repeated for 27 days. Cultures that grew at levels higher than the MIC were passaged on drug free MHA plates, and the MIC was determined. For teixobactin, there were no mutants with an MIC greater than the parent S. aureus ATCC 29213.
Moreover, there's a strong biochemical argument against resistance: the region that the antibiotic targets is highly conserved, which means that it's probably functionally necessary. The bug is therefore unlikely to evolve away from the threat. This is important, because it's that most likely avenue for antibiotic resistance, energetically speaking: it doesn't cost anything for an organism to mutate a weakly conserved gene, so they do it once, and pass it on to every subsequent generation with no penalty.
The antibiotic is just a peptide, so in theory you could see some sort of specialized peptidase evolve from an existing gene...but the problem is that the bug would have to then carry around that gene and express it constantly (or even less likely: evolve a sensing system that allows for selective expression). It's a highly unlikely thing, and virtually impossible to maintain over multiple generations without constant selective pressure. Bacteria do not like to hold on to genes that they don't need.
Nothing is impossible over evolutionary time, of course, but the researchers don't seem to be overstating their case here.
It's a highly unlikely thing, and virtually impossible to maintain over multiple generations without constant selective pressure. Bacteria are quickly out-competed by genetic variants with fewer expressing genes that they don't need.
BTW: do you have any links/data re the relative 'cost' of expressing unneeded genes?
Empirically, everyone who has done lab work with bacteria knows that they'll quickly (i.e. within a few generations) kick out plasmids unless there's selective pressure to keep them. Genes are more likely to stick around than plasmids (since they're directly integrated in the organism's genome, and there's less of an energetic cost to accumulating DNA sequence), but stable genome transformation is slow/unlikely, and bacteria will still find a way to disable un-needed genes in a relatively short period of evolutionary time.
Beyond that, even if they are out competed, that's not sufficient. They need to be out competed to extinction.
There's also regulatory genes that may be present, there are 6 known varieties of the whole gene cassette, with 5 further subtypes based on these regulators, so in the absence of β-Lactam antibiotics it sounds like a lot of them will be fit.
Nasty.
However, that does not exclude the possibility of the bacterium acquiring a plasmid or phage carrying an enzyme that inactives teixobactin. This particular mode of acquiring antibiotic resistance is quite common.
Nevertheless, this finding does seem to be quite a big deal. A novel broad-spectum antibiotic where spontaneous resistance is unlikely is a pretty powerful addition to the pharmacopeia.
Right, which is why I said the bit about bacteria kicking out genes that they don't need. Bacteria will "eject" a plasmid within a generation or two if they no longer need the gene(s) in question. Replicating a big gob of easily-ejectable DNA is not something bacteria do unless there's a good reason to do it.
Basically, for plasmid resistance to propagate, you need to have constant exposure to the antibiotic in question, or the resistance gene needs to be stably integrated into the bacterial genome. The former doesn't happen until an antibiotic is in extremely wide use, and the latter is one more rare step on top of an already unlikely chain of events.
It's not impossible, it's just unlikely.
Plasmids are indeed a source of resistance, but plasmids just contain genetic code. They are considered mobile since they are easily transferable between bacteria (including different species). So for a plasmid to encode resistance to this new antibiotic, it would need to contain the code for a protein which disrupts the action for the antibiotic. For example, the plasmid would encode for an enzyme that digests the antibiotic at a faster rate than it can work, or bind to the target of the antibiotic with a higher affinity.
So maybe what you were getting at is that a plasmid exists out in the world that encodes the protein for resistance, it just didn't happen to exist in the researchers niche world, or doesn't rely on a random mutation to become a resistance product.
Per cowsandmilk the senior author of the publication "is one of the world's foremost experts on antibiotic resistance". The paper discusses how there seems to be little gene transfer between the "biome" of soil bacteria from which this and vancomycin come and the relevant pathogens. They specifically cite that it took 30 years for any resistance to develop to vancomycin.
Whereas I'd add β-Lactam antibiotics seem to be pretty common (they are derived from at least 5 different organisms that I just counted in Wikipedia), and β-Lactamases are all too common; per Wikipedia https://en.wikipedia.org/wiki/Beta-lactamase the first was discovered in 1940 before penicillin was in clinical use.
I just described a very rough screening method, pcrh quotes from the Nature article other extreme efforts tried. These don't produce specific types of mutations, they just discover if there are any "easy" ones. E.g. the E. Coli antibiotic I mentioned had to be transported across the membrane bacterium by a protein.
The lab I did part of a summer's research was working with the enterobactin iron scavenging mechanism in E. Coli (https://en.wikipedia.org/wiki/Enterobactin). If grown in seriously iron free condition (e.g. glassware was soaked in HCl, and then bathed in deionized water for days), it would synthesize iron binding enterobactin and send it out into the environment, and there was a protein on the membrane surface that would accept the enterobactin+iron complex.
This also turned out to be the protein that accepted this antibiotic into E. Coli. It appeared that some of the mutations that allowed this were either point or deletion mutations of that protein, either it was deranged or cut off in some location, or outright deleted (missing from the bacteria's set of genes in its DNA).
So this survival mechanism is one of just not letting the antibiotic inside in the first place, which is how it appears teixobactin producing bacteria survive it. They appear to synthesize and expel it, and they don't have cell walls allowing it to get back in.
The reason we are having trouble finding new classes of antibiotics is that we are already have chemicals that target most of the interacting and essential cellular modules in bacteria. If you already are targeting 90% of all the possible targets you will find it very hard to discover any new classes of antibiotics.
Of course the solution is not to worry too much about finding new classes and just keep tweaking the current antibiotics to keep ahead of the bacteria. The only problem with this strategy is that the economics of antibiotic development is totally broken so the pharmaceutical companies have in the main stopped spending money on finding new antibiotics. What we need to work on is a new way of paying for new antibiotic development.
Plus drugs are one of the very most heavily regulated "free markets" in the US ... and as others have noted, there are laws like the Bayh-Dole Act (https://en.wikipedia.org/wiki/Bayh%E2%80%93Dole_Act) which can make the process much more of a government-non-profit-corporate partnership. There is also a "Generating Antibiotic Incentives Now" (GAIN) in effect, with an bipartisan Antibiotic Development to Advance Patient Treatment in the works.
So, no, we don't "just take whatever the free market finds profitable to provide", where "profitable" has "the visible foot" of the government strongly weighting one side of the balance scale. Not to mention very strong medical policy to restrict new novel antibiotics like this one to the cases where they're really needed.
There have been lots of proposals to overcome this. My personal favourite is each country agrees to pay a straight cash bonus for each new antibiotic developed with a different valued bonus in proportion to the need. The drug companies would then not need to worry if the antibiotic was used or not and we would have on tap new antibiotics to use as resistance arises.
This is a link to nature's new "share it for everyone to read if you have paid access to the article" version of 'open-access'.
A new antibiotic kills pathogens without detectable resistance, Nature, January, 2015. DOI: 10.1038/nature14098
Knowing nothing about this area... isn't this a bad idea because board use would increase the risk of resistance appearing and would mean those bacteria resistant to this would be extremely resistant to most other treatments aw well (given this drug has multiple modes of attack)?
Surely only using it in cases where other antibiotics hadn't proven successful would be a better approach so that you don't give bacteria much opportunity to become resistant.
Broad use of antibiotics in cases where it wasn't needed is exactly how we got into this problem in the first place.
Perhaps learning from history would be the most prudent approach.
I'm assuming their suggestion is to use this drug for the next 30 years, and by the time bacteria become resistant to it we can start using our old antibiotics again.
I'm not qualified to answer either way, I imagine several people could get PhDs finding out. It's too important to handle quickly
It's basically the same reason we don't fear bacteria to develop resistance to boiling or alcohol disinfectant.
A fast Google search gives this paper: " Relatively Alcohol-Resistant Mycobacteria Are Emerging Pathogens in Patients Receiving Acupuncture Treatment" http://www.ncbi.nlm.nih.gov/pmc/articles/PMC140401/
There are some archeas (and a few bacterias) that support boiling temperature, but IIRC they don't like meatware because it's too cold for them. http://en.wikipedia.org/wiki/Hyperthermophile
My thoughts exactly. Try using it in large scale animal farms for a couple decades and I'm betting something will become resistant.
Mycobacterium Abscessus, in particular is great at surviving in low-carbon environments (with very little food), and its protective shell and clustering formation protects it from low levels of chlorine. I cultured shower heads, sink faucets, and soda fountains in order to find them. Nasty stuff.
EDIT further down people are making the same point (I think)
edit: philwelch argues in a comment in this thread that this exact thing happens: https://news.ycombinator.com/item?id=8853769
It's an issue of selection pressures. If they live in a competitive environment, which includes competing against each other, then the most "fit" ones win by out reproducing the competition. Mutations that made them more fit in an environment rife with antibiotic X may be mostly harmless in the absence of X, or might consume resources that can ill be afforded. See e.g. this subthread for more discussion: https://news.ycombinator.com/item?id=8853232
Essentially if we stop treating with the drugs with resistances against them, we'd eventually end up with a bacteria gene pool that resembled the original pre-resistant one, where resistant bacteria were replication errors that were drowned out by natural selection.
The only issue is we can't do that without sacrificing millions of lives. So having a drug that works via completely different mechanisms would fulfil both.
Vancomycin is the drug of choice for several major infections that are of a concern to hospitals (MRSA, C. difficile) because there's already pretty established resistance mechanisms. There are definitely some "more last ditch" drugs, but Vancomycin is kind of the first of the "Now we bring out the big guns" antibiotics.
Partially because it's a PITA to give to patients, and has some toxicity problems.
To recoup your costs, you need to sell as much as possible--but in doing so, you render your own product obsolete due to continuing counter-evolution by the target species.
The idea is that drug resistance comes with a metabolic cost. We're making them do something to survive that we didn't before, and it's going to come at a cost.
If we think of them like cars--armoured ones are extremely rare. However, if we started randomly shooting at cars, and did so for a protracted period, we would eventually see them become more common. The fact they're slower, don't turn as well, and use more fuel is now negligible because of the excessive benefit of it's contents not being shredded.
If the implementation of this new antibiotic came with a moratorium on the prescription of penicillin, then we would be targeting the population as a whole with an RPG. It doesn't matter if you're armoured against bullets anymore. Both the normal and the resistant will be put under the identical survival pressures, which should mean it is more effective against the resistant strains as these won't be as fast to replicate.
The problem from what I understand is that tackling antibiotic resistant drugs with drugs designed for antibiotic bacteria, just makes super bugs.
Essentially if we cleared the roads of regular cars and left ourselves with armoured cars, and then start firing RPGs at them, we'll end up with vehicles resistant to those. We will end up with APC's on the road.
If we implemented a moratorium on penicillin strain antibiotics, we could potentially reverse the current epidemic of multi-drug resistant strains. It would be like starting anew - assuming there's no genes that are equally beneficial against both drugs.
That's my understanding of the reasoning behind suggesting broad use, but I could be way off.
Primates and guinea pigs both dropped the ability to synthesize Vitamin C, through different mutations. Now both species have to consume it in their diet to survive.
Incidentally, the story of the broken Vitamin C gene in primates and guinea pigs is the main argument that gets used to show how the theory of evolution is supported. In all primates, including humans, the gene to make Vitamin C is in our DNA, but mutated so that it is not usable. But all primates have the mutated gene in the same place. Guinea pigs have a different mutation to the gene. The chance that all primates had the mutation in the same location simultaneously is very remote, suggesting all primates shared an ancestor that developed the mutation.
Any new antibiotic makes this approach even better, because if you have A, B, C, D, and now E, now the bacteria has to be resistant to all five at once, which is a lot of useless genes to hold onto.
"The research was paid for by the National Institutes of Health and the German government (some co-authors work at the University of Bonn). Northeastern University holds a patent on the method of producing drugs and licensed the patent to a private company, NovoBiotic Pharmaceuticals, in Cambridge, Mass., which owns the rights to any compounds produced. Dr. Lewis is a paid consultant to the company."
If the research was paid for by the National Institutes of Health, why is the patent privately owned? This does not seem fair to taxpayers.
That seems like a well-formed feedback loop to me.
(This gets weird with the distinction between the researchers and the university as well, but that's a separate issue.)
While capitalism "won" these battles in the past and is better than authoritarianism, at the present moment, capitalism is destroying us all. Our version of capitalism is the new authoritarian regime evolving toward fascism. Like any authoritarian regime, our capitalism has effective marketing & it's believers.
"She died a famous woman denying her wounds; denying her wounds came from the same source as her power" -- Power, by Adrienne Rich (About Marie Curie)
So the answer is not as simple as sprinkling some "capitalism" on it. We need more love of self & others, more transparency, more equality, environmental protection, systemic design, awareness of the impact of our actions, awareness of politics, decentralization, less emphasis on money and more emphasis on community, etc.
"If you name me, you negate me. By giving me a name, a label, you negate all of the other things I could possibly be." -- Søren Kierkegaard.
The answer is not a label. The answer is our actions. That is who we are.
How do you propose to bring about a more utopian society with the above characteristics?
How plastic do you think human nature is?
(Note that I came of political age during the tail end of the cultural '60s. I have heard all of the above before....)
Individual people have to care about these values & resist the imposed values of ego, greed, competition, materialism, ridicule, nationalism, violence, being "right", "getting mine", etc. It takes people leading & living the life of these values. If others resonate with these new values, then a movement is built.
All I can do is love myself & others. I see my own life as an archetype of our greater successes & failures; doing my work has a positive impact on those around me.
> (Note that I came of political age during the tail end of the cultural '60s. I have heard all of the above before....)
Like anything else of nuance, it takes creative iteration.
The '60s changed our understanding of freedom, love, & compassion. The upheaval healed, perpetuated, & created trauma on our souls.
The '60s had a lot of energy breaking social bounds. Sex, drugs, & rock-n-roll, while liberating, is not necessarily the most sustainable emphasis.
Many people went down a more esoteric path learning about ego & love. We can utilize our advances in communication, social understanding, global reach, experience, etc to shift our values to be harmonious with each other & our environment. It's necessary to our survival, so I have faith that we will evolve, just like we have many times in the past (i.e. tools, fire, civilization, etc).
http://www.nature.com/nature/journal/vaop/ncurrent/full/natu...
The Scientist has quite a nice write up:
http://www.the-scientist.com/?articles.view/articleNo/41850/...
Details on the cell culture device (open access):
My son had cancer and he had a staph infection that was septic (AKA in his blood through out his body). Non-resistant = 95% cure rate resistant strain and if you have a compromised immune system less then 50% cure rate. Good news for cancer patients and glad to see it coming down the track.
Very glad to hear your son made it, and I echo your sentiment.
The other issue is that this is very early in development. I really hope it gets through trials, but there are graveyards full of promising antibiotics that failed.
Claims of major scientific break-through, yet is describing something at a very early stage of development
Nothing odd here, just the current state of scientific reporting.
Let's not hand this one out like candy and end up back against the wall like we are now.
Which is something easily (and safely) done in the lab and is part of testing any anti-biotic.
Now if this actually works then yes great, and I hope it does.
A new class would be great, but even different drugs from the same class would be great as well.
Also, assuming it doesn't have weird toxicity in people, or unfavourable pharmacokinetics, the author's suggestion that we should give it to everyone is a bit cute, given that it will almost certainly cost north of $200 per day if it gets to market...
Peptide antibiotics can have some issues. A recent new peptide antibiotic called Daptomycin [1] can't be used for pneumonia for example, because it is inhibited by pulmonary surfactant.
Genuine question--my experience is that a serious hospital stay racks up charges starting in the high five figures (and the sky's the limit), and if there's an antibiotic that's merely a couple thousand a day, it'd certainly be very cost effective.
This is USA specific. Day in hospital in Poland costs around 100-400 USD (and that's for people without insurance, so for >95% of population it's free). It's probably worse quality, but still..
I don't understand how you get so outrageus prices for healthcare in USA.
And in fact plants did not become resistant in the way they expected. Trouble is plants found a completely different way to resist roundup that no one expected.
Their claim that bacteria would not become resistant to this antibiotic is rubbish. They do have the ability to determine that.
If they actually want to know then deliberately try to (carefully) create resistant bacteria by continuously giving them low levels of antibiotic and slowly increasing it.
[1] http://www.npr.org/blogs/thesalt/2012/03/11/148290731/why-mo...
That's precisely what they did while investigating teixobactin, and they didn't see any resistance develop:
Was there a control? i.e. same procedure, but with a different antibiotic?
Kim Lewis, the senior author on this publication, is one of the world's foremost experts on antibiotic resistance. This isn't amateur hour.
But anyways, if it is an issue, why can't we just require antibiotics be taken intravenously? The vast majority of bacteria exposed to antibiotics are in your digestive system and that is where resistance develops. Or at least that's how I understand it.
IV antibiotics do have an effect on gut bacteria as well, it's not as simple as just not giving oral; additionally (and, perhaps the crux of the issue) is that gut bacteria exposure to antibiotics is not how resistance develops; and certainly aren't the main problem. It is the more common infective agents that cause the problems - Gram positive organisms (Strep Viridians, Staph Aureus etc) that usually enter from cuts or abscesses and, in the immunocompromised, cause significant disability.
How so? And more importantly how much antibiotics make it to the gut, vs if you take it orally? I would guess it would be a lot less.
>It is the more common infective agents that cause the problems
I know that, but as I understand it the resistance first evolves in gut bacteria, then spreads through horizontal gene transfer. Wikipedia cites this as the main cause of antibiotic resistance: https://en.wikipedia.org/wiki/Horizontal_gene_transfer
I have no idea what figure or percentage it would be, but for most common antibiotics which end up distributed in total body water, there will be a component that leaks into the gut through capillary action; if it is metabolised in the liver then a proportion of it will end up in bile (if fat soluble) and then enter the gut that way; either itself or a metabolite of it - it would be impossible for me to quantify and likely depends on many many factors such as molecular weight, structure and a host of other features.
Patients on IV antibiotics develop diarrhoea from IV antibiotics at a similar rate (from what I have experienced) to those on orals. hence it undoubtedly kills bacteria in a similar fashion.
And we use IV antibiotics to kill bad infections of the gut. So whatever the mechanism, if I have elucidated it or simply done some hand-waving, it clearly affects it significantly.
The only instance of antibiotic use that touches on what I feel you are pushing for is the use of oral vancomycin (It is almost always IV) for severe bacterial infections of the gut - we use it oral because it is not absorbed systemically (as opposed to other specifically oral antibiotics) so doesn't cause systemic effects.
> then spreads through horizontal gene transfer.
Sure. But if you look at how they tested this particular antibiotic for the ability to develop resistance, they exposed TB and Staph to sub-theraputic doses for 27 days, or (for Staph) or 810generations (assuming a rough rate of division somewhere around 40 min to 1 hr in ideal conditions). An epic number of cell divisions if you work it out (and I can't).
The commonly accepted knowledge, as far as I understand it and as far as I have been taught it, whether or not bowel bacteria have a significant role to play or not, is that exposure of antibiotics to sub-lethal doses for long periods of time promote the survival of strains that have a competitive advantage against the agent in use, which over time allows the strain to survive in otherwise-lethal doses, and that gene becomes incorporated into a plasmid and then ends up spreading to every other organism capable of horizontal gene transfer.
Anyway, I am at home and not going to see the next MD, PhD in Infectious Diseases until tomorrow but when I do I will ask him and reply here. So, check back in 24 hours if you're interested
There are several problems with IV antibiotics, some of which have been outlined in other comments:
1. It involves an IV. This means a hospital - that's both expensive for all involved, and the presence of an IV is in and of itself a risk for bacterial infection. Not all antibiotics kill all bacteria.
2. "The vast majority" = / = the ones experiencing resistance that are of clinical concern. C. difficile lives in your gut. MRSA on the other hand can live on your skin, and colonize your nasal passages. Both, additionally, cheerfully live on surfaces for quite some time (really quite some time for C. difficile).
3. IV antibiotics can reach your gut - some are excreted into the intestines. Metronidazole is, vancomycin isn't for example. And beyond that, much of the concern is with active infections, which are very likely not in your gut for many diseases, in contrast to just the background of your intestinal flora.
4. You're asserting that antibiotics reaching your gut from an IV would arrive in low doses. That's a good thing for promoting the development of resistance, not a bad thing, from the bacteria's perspective.
I'd much rather get two or three more that all use different mechanisms, and use them as a cocktail.
Let the bugs try to develop 3 different kinds of resistance at once.
Remember there's about 10^14 bacterial cells in the average human body, ten times the number of human cells. Everyone's a big petri dish. If you killed all but one in a billion you'd still have a whole bunch left.
I've heard the following causes, but I cannot substantiate them:
[1] Improper patient usage. Primarily, not taking the prescribed dosage long enough to eradicate all of the target bacterium, leaving (enough) survivors to meaningfully propagate their resistance. Typical to the "Hey I think my sinus infection is gone already! Adios remaining pills."
[2] Improper targeting. A functional antibiotic used on the wrong type of bacterium, or even usage against viruses.
Are there any others? Are my [1] and [2] debunked?
2. This is also a thing - broad spectrum antibiotics, difficulty in diagnosing, patients wanting something even if their infections are viral, etc. all lead to mistargeting of antibiotics for a number of reasons. Antimicrobial stewardship has become a major part of hospital infection control.
3. The widespread use of antibiotics in livestock. The agricultural use of antibiotics is staggering
What the market needs is a placebo anti-biotic. One thats totally wasted by resistance so it won't hurt anything, and is reasonably cheap. Give it some nasty digestive system "effects" as a special gift to patients dumb enough to demand a pill against medical advice. Something that is, in fact, an antibiotic, so when they go home and look it up on wikipedia they don't freak out when they find out what a sucrose pill is. Maybe a homeopathic dose of it, so counter-reactions are rare and minimal.
I don't remember the specific documentary but here is a wikipedia link [2] "Although extensively used and developed mainly in former Soviet Union countries circa 1920, the treatment is not approved in countries other than Russia and Georgia."
Ultimately, developing antibiotics is a cat-and-mouse game, and eventually nanotech will render it archaic, but in the mean time the more we can do to be responsive and quick to adjust, the better, and that means new antibiotics.
I do worry about this "30 year projection" and what that's based on. Is that a historical norm?
What we should be doing is addressing the cause of antibiotic resistance in the first place, namely the overprescription of antibiotics, and their improper use in industrial farming.
Which for all practical purposes might be the same thing, if we're talking 80 years versus 30 years for propagation of resistance.
Nanotech will be a very, very arduous and slow process. "Its own problems" is putting it lightly. People will die due to nanotech approaches to anti-pathogenics, no question about it. We're talking about programmable biology, something will go wrong.
The biggest problem is what happens when we've eliminated human pathogens? What happens when we've extended the average life expectancy by 10 years - after all, many cancers are caused by pathogens. What happens to the ecosystem when herpesviridae is effectively gone? What are the side effects, the unintended consequences?
Mimicking nature is exactly what got us into this problem in the first place.
As noted in another comment, the underlying Nature article is up on the World Wide Web, [after edit:] and now shared to all of us by a subscriber who posted a subscriber's-sharing link in this thread.[1] I searched for some other news stories about this preliminary research finding to link to others based on independent reporting as well as the authors' press release and the Nature article. I found a story in Financial Times[2] reporting, "Teixobactin quickly kills Gram-positive bacteria, which are prominent in discussions of antibiotic resistance, including Clostridium difficile, Mycobacterium tuberculosis and Staphylococcus aureus.
"Neil Woodford, head of the antimicrobial resistance unit at Public Health England, commented:
"'The rise in antibiotic resistance is a threat to modern healthcare as we know it, so this discovery could potentially help to bridge the ever increasing gap between infections and the medicines we have available to treat them.'
"But Prof Woodford added: 'Although it is a step forward, this new discovery would not be suitable for treating infections caused by E. coli, Klebsiella or other Gram-negative bacteria.'"
The Washington Post reports,[3] "But all good things must eventually come to an end.
"'They didn't find resistance in a couple of simple tests, so it won’t happen in a minute, but there is no compound on this planet that bacteria will not develop resistance to,' Said Richard Novick, an NYU Langone Medical Center professor who wasn't involved in the study. 'But it would certainly happen more slowly with this one.'
"And unfortunately, the drug's genius mechanism is also its biggest flaw. It can only target so-called gram-positive bacteria, like staph, strep, and TB, because they're unprotected once their cell wall starts to break down. Gram-negative bacteria like E. coli and the organisms that cause many sexually transmitted infections have an outer membrane that Teixobactin can't penetrate. That's probably a safety mechanism built-in by the gram-negative bacteria that created Teixobactin in the first place."
That expert also comments that he would strictly limit application of this antibiotic at first to hospital settings, and that would be my policy recommendation too, to reduce the chance of producing selection pressure for resistant strains of bacteria. But this does look like it could be a big advance in clinical treatment of gram-positive bacterial infections resistant to other antibiotics.
The reporting in The Scientist,[4] already linked by an earlier participant, includes a comment on the laboratory technique used to find the microorganism that produces this new antibiotic: "'This is a very clever technique,' added Robert Austin, a physicist at Princeton University who studies the evolution of microbes and was not involved in the current study. 'The bacteriology community needs to get away from culturing bacteria on agar plates, because this will not lead to new antibiotics.'" That's a familiar principle in science: look in a new place, and make new discoveries.
The reporting in The Guardian[5] picks up on that idea in the words of another expert: "'What most excites me is the tantalising prospect that this discovery is just the tip of the iceberg,' said Mark Woolhouse, professor of infectious disease epidemiology at the University of Edinburgh. 'It may be that we will find more, perhaps many more, antibiotics using these latest techniques.'"
It's very likely that there are more antibiotics yet to be discovered, because all microorganisms live in a world full of other microorganisms, and haphazard adaptation to that environment must have produced selection pressure for many microorganisms to produce natural chemicals ("antibiotics") that kill off other kinds of microorganisms. Putting those chemicals into human bodies applies human knowledge to take advantage of the variety of life that has arisen from evolution.
"A new antibiotic kills pathogens without detectable resistance" http://www.nature.com/nature/journal/vaop/ncurrent/full/natu...
DOI: 10.1038/nature14098
[2] http://www.ft.com/intl/cms/s/0/701a3c36-95be-11e4-a390-00144...
[3] http://www.washingtonpost.com/news/speaking-of-science/wp/20...
[4] http://www.the-scientist.com/?articles.view/articleNo/41850/...
[5] http://www.theguardian.com/science/2015/jan/07/antibiotic-dr...
> Scientists have discovered an antibiotic capable of fighting infections that kill hundreds of thousands of people each year
Given it's potential as a medicine, the media will hype it into public consciousness. Marketers & Entrepreneurs will use this social inertia to sell it in places where it is dangerous to use. The FDA has a history of revolving doors with big pharma & playing loose in pandering to corporate interests, at the expense of the public & environment.
I'm merely presenting a minority view here on Hacker News. It's good to have all your t's crossed and i's dotted.