New antibiotic kills off persistent infections

http://phenomena.nationalgeographic.com/2013/11/13/killing-sleeper-cells-and-superbugs-with-assassin-janitors/

by oyvindeh • 13 years ago

187 84 13 years ago

phenomena.nationalgeographic.com

sgarlatm• 13 years ago

It's nice to know that despite all the alarmist articles about the end of antibiotics, good progress is being made. If this works, it could completely replace traditional antibiotics. In that case, I could see dozens of new drugs in this class developed by the antibiotic companies. This would be similar to the race to develop new antidepressants, HIV drugs, and erectile dysfunction drugs. Any drug you have to take over and over again is a huge draw for the pharmaceuticals.

zabraxias• 13 years ago

This is really fantastic news but I too am skeptical of the drug companies being interested in a cure as opposed to a repeatable treatment.

As a side note the article seems very well written for non-medical folks like myself.

Fomite15• 13 years ago

This line of reasoning doesn't really apply to antibiotics - because you're likely to get another infection in your lifetime, and many people have infections at any given time, they're perfectly fine eradicating this one.

Believe me, in the infectious disease space, drug companies tend to look for cures and prevention. For example, Merck and GSK spent staggering amounts of money on the HPV vaccine.

giarc5• 13 years ago

This won't completely replace traditional antibiotics. As the article states this acts on Gram positive persister cells (a very specific group). The coming storm is from Gram negative bacteria such as Klebsiella, Actinetobacter and Pseudomonas.

There is actually very little activity occurring in the field of antibiotic drug discovery and you identified the issue; no money in drugs that someone takes for 14 days and stops. Pharmaceutical companies are driven by stockholders and therefore they want them developing drugs that someone takes for the rest of their life (anti-depressants). Much of the research for abx discovery comes from academia who struggle with budgets that are pennies compared to what Pfizer, GSK, Wyeth, Astra can afford.

im3w1l• 13 years ago

The scary thing is what would happen if these bacteria fell into the hands of terrorist extremists. They could potentially create bio-weapons of mass destruction. Or imagine if some suicide cult decided that the time has come for the doomsday of reckoning. Al-Qaeda anthrax letters are nothing compared to this. It could also be used to threaten mutually assured destruction in asymmetric warfare. Iran could probably develop it more easily and stealthily than their (not very) secret nuke program. Developing countermeasure to this is a matter of national security. Insha'Allah people will come to their senses and please think of the children: We must secure the existence of our people and a future for white children before it is too late.

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JunkDNA2• 13 years ago

You're right that it's about profits when pharma is involved, but you are wrong about the reason (otherwise vaccines would not exist). I can tell you from firsthand experience that the length of time someone is on a drug makes almost no difference in where research priorities are.

The primary issue with antibiotics is that since the late 1990's, if you succeed, and you develop the best antibiotic the world has ever seen, the FDA will require it to be a "drug of last resort". It will therefore sit on the shelf and be guaranteed to not be prescribed very much during the life of its patent. Once enough time goes by, and other drugs come out if (and that's a big if) it is no longer a drug of last resort, it is likely off patent and therefore can be made in generic form for pennies by generic manufacturers. Regardless of what you think about patents, these incentives are completely misaligned with companies going all-in and taking a risk on new antibiotics.

w1ntermute• 13 years ago

Sounds like something the Gates Foundation should get on.

larrys• 13 years ago

"no money in drugs that someone takes for 14 days and stops. Pharmaceutical companies are driven by stockholders"

You wonder of course why, if that is the case (and I do agree), that the government doesn't get involved with more funding or subsidies for these types of less profitable drugs. The same way they spend countless dollars on other things for the public good (and company profit obviously).

spindritf3• 13 years ago

it only works the bacteria known as gram-positives, which includes problematic bugs like Staphylococcus

I have had one of those for almost a decade now.

He hasn’t tested it in humans yet

How long is the road ahead before it becomes available to regular patients? Should I get my hopes up?

unclebucknasty4• 13 years ago

I have had one of those for almost a decade now.

Sinuses?

spindritf3• 13 years ago

No, just an ear infection. More annoying than anything. Although it does supposedly carry some risk of hearing loss should it come back hard.

giarc5• 13 years ago

It's going to be a long time before it is readily available for human use. Expect three, maybe four stages of clinical trials. There is also the risk that it doesn't even work in humans or has major side effects that outweigh the benefit.

This is sensationalism news, or as it is most often called, news.

javanix• 13 years ago

I would call it a sensationalist title, but the article itself is far from sensational.

I actually found the writing to be pleasantly balanced and scientifically detailed, without jumping to unreasonable conclusions.

emiliobumachar• 13 years ago

Consider writing to the researchers volunteering for a clinical trial.

It does, of course, involve a certain risk. You should do a lot of thinking before taking such a leap.

throwaway0094• 13 years ago

New antibiotic kills off persistent infections

Now available in hand-soap.

angersock• 13 years ago

oh god damn it >:(

Brakenshire2• 13 years ago

What's that? Inject the hand-soap directly into my veins?

AaronFriel2• 13 years ago

The most understated portion of the article is that there is a method discovered that can kill biofilms. The discovery of new antibiotics and delivery techniques leaves me less optimistic for long-term change in the availability of life-saving antibiotics. I suspect bacteria can, and will, evolve around almost any mitigating technique we develop.

Yet I'm optimistic, because tools that crack biofilms are a new are of development and promise hope for exploring new attacks on bacteria. Current methods of biofilm dispersal are application of strong acids and bases or an autoclave. You can't treat a hospital room with an autoclave, and comprehensive treatment of a room with very strongly ionizing agents has its own risks. There are other, experimental methods, but all are worth examining.

I hope research like this continues.

_Adam3• 13 years ago

I suspect bacteria can, and will, evolve around almost any mitigating technique we develop.

That's a baseless suspicion. Bacteria are ultimately bound by physical laws, and while they've proven resilient, there's no reason to suggest we will be unable to develop the means to annihilate them at will. Humans are creative - bacteria just evolve fast.

I agree about the importance of the biofilm claim, but what they don't explain is how they actually achieve this. Their method of disabling that particular protein doesn't directly address the problem of the biofilms having a less-permeable extracellular matrix.

gnaffle• 13 years ago

What I'm more concerned about is that new, creative innovations (nanobots etc) can have more sinister uses and might ultimately prove a bigger risk than our current bacteria.

AaronFriel2• 13 years ago

The problem of killing bacteria, as I see it, will increasingly become something akin to the demarcation problem of philosophy. Why would it not be? It is natural that the optimal situation for pathogenic bacteria to be in is one in which they are indistinguishable from necessary cells. It may take an extraordinarily long time, but until we are able to completely eradicate a pathogenic bacteria from the earth, we will remain in that arms race.

Humans are creative at killing bacteria, though it's already not difficult to "annihilate them at will". It's much harder to annihilate only the ones we don't like, only the ones that harm us, and only the ones that pose the greatest risk.

crusso• 13 years ago

Humans are creative - bacteria just evolve fast

Yeah, but once we get good enough to annihilate them at will we will also have a similar power to improve them through tinkering.

Just like computer viruses continue to be developed by people, biological agents will be developed as well.

Some human tinkering will be for the heck of it. Some will be government level projects that get out of control. Eventually, organized crime will be in on the action.

Imagine Cryptolocker (http://en.wikipedia.org/wiki/CryptoLocker) but with a biological agent.

joe_the_user4• 13 years ago

I agree that we humans don't have to expect bacteria to always evolve methods to resist our medical interventions. However, I think the most effective thing, maybe the only, we can do is actually look at the process of bacterial evolution.

That is, unless antibiotics are wildly over-used and human pathogens are concentrated in one place facing constant medical intervention, human medical intervention is going to be a very small, unimportant part of bacterial evolution.

Unfortunately, antibiotics are widely over used and pathogens are concentrated in poor administered hospitals.

If we stop these practices and we could stop these practices, then antibiotic-resistant bacteria would have little evolutionary incentive to exist.

ImprovedSilence• 13 years ago

killing bacteria alone isnt a problem. Killing bacteria while keeping a human alive starts to complicate the problem. Killing certain bacteria while keeping a human and the rest of said humans helpful bacteria alive but not resistant to anti-bodies, is a whole different ballgame...

rsync• 13 years ago

"You can't treat a hospital room with an autoclave"

Hmmm... that sounds like an awfully good idea, actually...

Build the hospital room with the ability to be airtight, make sure all materials can withstand 134 C (or remove things that can't for their own cleaning) ... and autoclave the room ...

joe_the_user4• 13 years ago

There are simpler things.

Like not having mega-hospitals that are impossible to keep entirely clean.

Growing up near the UCLA Medical Center, a vast, vast complex, I heard tales that there were diseases that existed there and nowhere else in the world. Most patients derive little benefit from the scale of the hospital and the fact that in a huge hospital getting all rooms clean at once is logistically very difficult means that scale can be very dangerous.

jlgreco• 13 years ago

Hospital rooms with built-in autoclaves would give horror movies a lot more material to work with...

Fomite15• 13 years ago

There's also some research into surfaces that combat the formation of biofilms.

mjn• 13 years ago

Some background, based on quick research, not personal knowledge, so please correct if anything's wrong:

This class of antibiotics, ADEP, was discovered as a naturally produced substance isolated from the bacteria Streptomyces hawaiiensis in 1985 (Streptomyces has been a fertile source of naturally occurring antibiotics). After some promising results, there was work on synthetically synthesizing it and producing "optimized" synthetic variants. ADEP4 is one of those, and was reported in a paper published in 2005. There's a short 1-page summary of that work in Nature Reviews Drug Discovery 4: 957. See page 19 of this PDF, article "Peptide power": http://journals2005.pasteur.ac.ir/NR/4%2812%29.pdf

There's a lot of work trying to understand its mechanism, e.g. here's one open-access paper that also has some background: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2955292/

Here's the paper discussed in the linked article, unfortunately paywalled, but with an abstract available that's actually a good summary: http://www.nature.com/nature/journal/vaop/ncurrent/full/natu...

Brakenshire2• 13 years ago

isolated from the bacteria Streptomyces hawaiiensis in 1985 ... ADEP4 is one of those, and was reported in a paper published in 2005 ... [potential trials in coming years]

Gives an idea of the sort of development timescale we're talking about. It's almost 30 years from isolation to this point. Clinical trials would take another 10-15 years. So, if all goes well, that's 40 years from the initial discovery until a doctor starts making up prescriptions.

ChuckMcM• 13 years ago

Excellent summary. I look forward to when our knowledge of cell biology is so complete that there isn't any time wasted on 'trying to understand its mechanism' rather we can explain such mechanism from first principles and know with certainly not only how it works, but how to adjust it to work most effectively to our benefit.

girvo• 13 years ago

It's a peptide? Neat!

atmosx• 13 years ago

That's very good news actually. If first stage trials are successful might be marketed sooner than expected. However, I didn't read the paper, so I can't comment on the mechanism of action which the mos interesting part of an drug. Bacteria might become resistant if this procedure becomes overused (as usual) and it would be a shame.

driverdan• 13 years ago

Very interesting research but it doesn't mention any negatives of ADEP4. What kind of effects could it have on the human body?

Fomite15• 13 years ago

Many antibiotics are fairly nasty drugs - they're associated with kidney failure and other negative outcomes, especially for long term treatment. But it's hard to know for sure until things progress to the point where we are doing toxicity studies.

Which you don't bother with until you know the thing can work in the first place.

davidjnelson• 13 years ago

I wonder if this approach will eventually be useful in eliminating Chronic Lyme Disease.

Fomite15• 13 years ago

Doubtful, as there's little to no scientific evidence that Chronic Lyme Disease is actually a bacterial infection.

brandoncarl4• 13 years ago

That's actually a bit of a dated response:

See recent study on Rhesus monkeys: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjourna...

The "no bacteria" perspective is usually based off of IDSA guidelines. Unfortunately, they've been successfully litigated against for providing incorrect information that appear to be linked to financial interests:

"My office uncovered undisclosed financial interests held by several of the most powerful IDSA panelists. The IDSA's guideline panel improperly ignored or minimized consideration of alternative medical opinion and evidence regarding chronic Lyme disease, potentially raising serious questions about whether the recommendations reflected all relevant science."

http://www.ct.gov/ag/cwp/view.asp?a=2795&q=414284

Good summary of Lyme: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3636972/

Needless to say, we've got a lot of people we're telling that they are not sick when symptomatically they appear to be.

evacuationdrill2• 13 years ago

Hm, that's interesting.

"Approximately 10 to 20% of patients treated for Lyme disease with a recommended 2–4 week course of antibiotics will have lingering symptoms of fatigue, pain, or joint and muscle aches. In some cases, these can last for more than 6 months. Although often called 'chronic Lyme disease,' this condition is properly known as 'Post-treatment Lyme Disease Syndrome' (PTLDS).

The exact cause of PTLDS is not yet known. Most medical experts believe that the lingering symptoms are the result of residual damage to tissues and the immune system that occurred during the infection. Similar complications and 'auto–immune' responses are known to occur following other infections . . .

Regardless of the cause of PTLDS, studies have not shown that patients who received prolonged courses of antibiotics do better in the long run than patients treated with placebo."

http://www.cdc.gov/lyme/postLDS/index.html

scottrudy• 13 years ago

can it be tested on Google+?

jes5199• 13 years ago

Reading about new treatments gives me a kind of anxiety: drug trials are so slow and the funding models are so removed from the actual human life-saving potential, that I just am filled with fear that this stuff will get mired in bureaucracy or otherwise defunded rather than getting FDA approved. I dread the idea that someone I know to get sick and die because we're so ploddingly slow at doing these trials.

For example: "DRACO" antivirals from MIT, were developed in 2011, and according to mouse model tests and tests on cultured human cells, is safe and effective against influenza and rhinovirus and everything else they threw at it (see http://mackinstitute.wharton.upenn.edu/wp-content/uploads/20... for details), and yet it could be a decade before we even try to answer questions like "wait, does this cure HIV? It sounds like it might actually cure HIV"

Fomite15• 13 years ago

The funding models actually aren't removed from the actual human life-saving potential. The NIH has been pushing translational research pretty heavily, and if anything there's been a fair amount of pressure on the basic science types to tie their research to something, anything that will manifest in Saving Lives.

Beyond that, it absolutely should take drugs many years to come to market. Research is hard. Research on human beings is very hard. You can't just take shots in the dark and hope something sticks - you have to understand how, and how well, something works. Even for the established antivirals we do have for HIV, we're still trying to figure out who to give them to and when.

Houshalter• 13 years ago

The bacteria evolving to go dormant reminds me scale insects that damaged citrus fruits. The farmers put a giant tent over every tree and gassed them. This worked at first, but after a few years the scale insects got resistant. Whenever startled, they would sit perfectly still and hold their breath for half an hour.

ffrryuu• 13 years ago

But does it kill the host as well?

shawn-furyan• 13 years ago

This is an awful headline change. National Geographic's title (Killing Sleeper Cells and Superbugs with Assassin Janitors) wasn't very descriptive, but at least it didn't leave room for a headline browser to take away the false conclusion that the CDC declared public health crisis of antibiotic resistance is near resolution.

According to the article, this new antibiotic has only been tested on mice and rats. These sort of preliminary results go bust all the time, and so I think that in this case, it's irresponsible to fail to indicate that these are preliminary studies and that the effect hasn't been demonstrated in humans. This could have been achieved by leaving the title the same, or by changing it to "New antibiotic kills off persistent infections in rats".

analog31• 13 years ago

If this is a novel antibiotic with any therapeutic potential, please let's outlaw feeding it to cattle by the ton.

GoodIntentions• 13 years ago

Pretty much exactly what I was going to post. Prophylactic use of antibiotics in hogs/whatever is stupidity in a class of its' own, selectively breeding organisms on an industrial scale for resistance to the drugs we might want to use to keep us alive.

New antibiotic kills off persistent infections

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