Killing superbugs

[pendell]

As seen in science alert (http://www.sciencealert.com/the-science-world-s-freaking-out-over-this-25-year-old-s-solution-to-antibiotic-resistance)



Shu Lam, a 25-year-old PhD student at the University of Melbourne in Australia, has developed a star-shaped polymer that can kill six different superbug strains without antibiotics, simply by ripping apart their cell walls.

"We’ve discovered that [the polymers] actually target the bacteria and kill it in multiple ways," Lam told Nicola Smith from The Telegraph. "One method is by physically disrupting or breaking apart the cell wall of the bacteria. This creates a lot of stress on the bacteria and causes it to start killing itself."

The research has been published in Nature Microbiology, and according to Smith, it's already being hailed by scientists in the field as "a breakthrough that could change the face of modern medicine".


So what did you do for your doctoral dissertation? :smallamused:

Respectfully,

Brian P.

[Jothki]

That just means that superbugs are soon going to be able to resist that as well.

Still, though, the more things that a bacteria puts effort into resisting, the more limitations they'll have on functioning in other ways.

[Douglas]

That just means that superbugs are soon going to be able to resist that as well.

Still, though, the more things that a bacteria puts effort into resisting, the more limitations they'll have on functioning in other ways.
Sooner or later the mutations that develop to resist the newest medicine will result in losing resistance to an old one, and that's when we really win the antibacterial arms race.

[Grinner]

Sooner or later the mutations that develop to resist the newest medicine will result in losing resistance to an old one, and that's when we really win the antibacterial arms race.

That's already a thing, actually. Turns out that between antibiotics and bacteriophages (bacteria-specific viruses), bacteria can only maintain resistance to one or the other, not both. In fact, bacteriophage research is presently undergoing a revival for its possible medicinal applications.

[Knaight]

I wouldn't get my hopes too high just yet - things that work on mice and fail on humans are routine in medical testing, there's a lot of winnowing at every stage.

With that said: while the article uses cell wall and cell membrane interchangeably (which is obnoxious), if it is the cell wall targeted that's a good sign for specificity - peptidoglycan isn't exactly ubiquitous in human cells. The use of a non-antibiotic method is also promising.

[pendell]

Fun fact: One theory is that the magic spell 'abracadabra' was originally created to destroy disease (http://www.todayifoundout.com/index.php/2013/11/origin-word-abracadabra/). To kill, annihilate, whatever it was that was troubling the body. Funny how the tools change but the basic principles remain the same over the centuries.

.. So does that make our researcher a wizard? Should we give her a pointy hat? :smallamused:

Respectfully,

Brian P.

[Khedrac]

Physical attack on bacteria has been known about for a while - it is why wooden chopping boards are actually usually healthier than glass and definitely healthier than plastics.
The little spikes of wood tend to poke holes in bacteria successfully killing them even though the rough surface makes them hard to clean.
Glass's smooth surface is easy to clean.
Plastics tend to develop a rough surface which is hard to clean without the sharp points that kill the bugs...

There are actually lots of old 'traditions' that tend to make a real difference when studied with modern knowledge.
Another good example is the preference for silver cutlery for those who can afford it - silver is naturally anti-microbial.

[Yora]

Matters rather little for cuttlery. But it's wonderful for surgery tools. Silver does indeed make magical blades. :smallwink:

There's also been a trial in which brass door handles significantly reduced infections in hospitals. They are probably the most touched surfaces by the largest number of people you find anywhere in a hospital and brass is also a really awful surface for bacteria.

[Porthos]

Hmmm....

From the article:


Unlike antibiotics, which 'poison' bacteria, and can also affect healthy cells in the area, the SNAPPs that Lam has designed are so large that they don't seem to affect healthy cells at all.

"With this polymerised peptide we are talking the difference in scale between a mouse and an elephant," Lam's supervisor, Greg Qiao, told Marcus Strom from the Sydney Morning Herald. "The large peptide molecules can't enter the [healthy] cells."

Okay, great. But do the SNAPPs stay in the body (presuming they are actually put inside a human to attack bacteria)? Like, forever? Dunno, my 'unintended consequences' sense is tingling. I mean, I know these folks are a hell of a lot smarter than me, but it's one of the first thing that comes to mind: What happens five, ten, fifteen years down the road as these things keep bouncing around inside a person?

Obviously a short article like that isn't going to cover everything. Still, something that came to mind.

[Lord Torath]

Or, if they do pass from the body, what happens then? They presumably make their way to the wastewater treatment plant, where they are either filtered out and added to the solids handling - generally ending up as compost - or pass through, ending up in the waterways. What effects will they have on the micro-biospheres they encounter? Microbeads (used for a time in cosmetics) have a harmful effect on microorganisms, and I don't see these being any easier on then. Further testing is definitely called for.

[Porthos]

Or, if they do pass from the body, what happens then? They presumably make their way to the wastewater treatment plant, where they are either filtered out and added to the solids handling - generally ending up as compost - or pass through, ending up in the waterways. What effects will they have on the micro-biospheres they encounter? Microbeads (used for a time in cosmetics) have a harmful effect on microorganisms, and I don't see these being any easier on then. Further testing is definitely called for.

Great point that I hadn't thought of. Basically the enviornmental impact.

Reminds me of a perhaps apocryphal take that back in the day, the arrival of gas powered cars were welcomed in part because then cities wouldn't smell so foul from all of the horse crap that lined the streets (even if you had regularly scheduled pickup, the smell still was there until it was dealt with).

An article here (http://www.banhdc.org/archives/ch-hist-19711000.html) talks about the phenomenon.

That's what I also meant about 'unintended consequences'.

And while I'd like to think we're smarter (or at least more saftey aware) than we were back in the day (and we are in fact), I can't help but think of the problems that CFL lightbulbs caused. Whose, ahem, bright idea was it to mass produce a highly fragile product that has an, ahem again, insanely dangerous chemcial (mercury)? When I first found out about the risks of mercury poisioning from shattered CFL blubs, I just had to wonder how they hell they ever got approved. As well as wonder why people weren't being mass educated about the hazard caused by shattered CFL bulbs.

Thankfully we now seem to be quickly shifting to LED lights, but even that might have issues.

[halfeye]

Sooner or later the mutations that develop to resist the newest medicine will result in losing resistance to an old one, and that's when we really win the antibacterial arms race.

If that's winning.

It's interesting that cancer took off big time when penicillin became widely used. There's the new recognition that our gut bacteria influence our ability to lose weight, and that they tend to get trashed in the crossfire when we take antibiotics to deal with a dangerous infection.

I don't know what the situation is with bacteria, but I suspect we don't really want to be sterile.

[Knaight]

It's interesting that cancer took off big time when penicillin became widely used. There's the new recognition that our gut bacteria influence our ability to lose weight, and that they tend to get trashed in the crossfire when we take antibiotics to deal with a dangerous infection. As far as cancer goes, cancer took off when life expectancy went up - and if you look at cancer rates by age, and consider the whole mutation accumulation mechanism that makes a great deal of sense without penicillin somehow causing it. As for gut bacteria, they're absolutely critical, but some casualties there to deal with something dangerous is generally a good thing.


I don't know what the situation is with bacteria, but I suspect we don't really want to be sterile.
We need our microbiomes, and the overuse of things like antibacterial soaps caused a problem here. That doesn't mean that antibiotics are a bad idea for when you actually have nasty bacteria that you need to get rid of.

[Spiryt]

Or, if they do pass from the body, what happens then? They presumably make their way to the wastewater treatment plant, where they are either filtered out and added to the solids handling - generally ending up as compost - or pass through, ending up in the waterways. What effects will they have on the micro-biospheres they encounter? Microbeads (used for a time in cosmetics) have a harmful effect on microorganisms, and I don't see these being any easier on then. Further testing is definitely called for.

I imagine that if they were used to kill superbugs, they would be used in hospitals, on badly ill patients, in strictly controlled environment?

Everything patient excretes is handled, filtered/destroyed etc. Not just released into the sewage?

[Grinner]

I imagine that if they were used to kill superbugs, they would be used in hospitals, on badly ill patients, in strictly controlled environment?

Everything patient excretes is handled, filtered/destroyed etc. Not just released into the sewage?

No, that sounds too expensive for just bacterial infections. There's nothing special about so-called superbugs except their unusually strong antibiotic resistance. With any antibiotic replacement, we'd ideally be able to use them in the same capacity.

[tantric]

That's already a thing, actually. Turns out that between antibiotics and bacteriophages (bacteria-specific viruses), bacteria can only maintain resistance to one or the other, not both. In fact, bacteriophage research is presently undergoing a revival for its possible medicinal applications.

this concept is why the three drug cocktail continues to work against hiv. in grad school we actually had to model the evolutionary logic as to why the virus would never develop resistance to all three drugs.

my dissertation, which i never finished, involved modeling multiparasite infections using ecosystem models, particularly helminths in white tailed deer.

[Dodom]

I tried to click the sources of the article but got a page not found on one side and a paywall on another, so unfortunately I'm replying without knowing all the available technical details.

I'm fairly optimistic about the risk of such a molecule accumulating in the environment or even the body. Peptides are, to simplify, smaller proteins. There's usually *something* that can digest those, though it can take a while in some cases (keratin is a protein and it still clogs drains; there ARE tough ones).

Peptides as a class have downsides too: they're easily allergenic, don't cross anatomical barriers easily and they might be too digestible to take orally.
Not crossing an anatomical barrier easily is both a pro and a con: while it means there are organs it can't reach (no good for UTIs, especially), it also means having it in one place might not wreck your flora some other places.

I think it's a bit premature to say bacteria won't develop a resistance. Since it attacks the cell wall, bacteria that have a natural resistance to penicillin might resist it similarly: Mycoplasma, because it has no cell wall, Mycobacteria, because of their waxy mycolic acid layer, and some gram negative bacteria, because their cell wall relies on lipids more than peptidoglycan for its structure. Being a new class of antibiotic, we should be clear of acquired resistance for a while, but I wouldn't bet on it never happening.

Also he lack of cytotoxicity doesn't mean it won't have toxic effects on a whole body. Many existing peptidic antibiotics are seldom used internally because they're nephrotoxic. No need to enter cells for that, a lot of things can mess with a glomerulus basal membrane directly. So I'd rather see a thorough clinical study before concluding that disease has been banished forever.


Finally...
I hope we'll be seeing a follow up of that. A new class of antibiotics is good news, but the press might lose interest if it's not a panacea.
Many years ago, the idea of separating stereoisomers made the news: chemically synthetised molecules are racemic mixtures, but often, only one isomer is active, while both contribute to toxicity; eliminating the useless isomer doubles the effective dose without increasing the side effects and risks.
Pretty exciting idea right? So what happened with it?
It went on, a couple drugs with new commercial names appeared, and what was in fact a small revolution in antibiotic use went unnoticed to the public, because "Maybe we'll cure all diseases forever!" makes better headlines than "We actually improved our handling of infections, no maybes, we did it!"

[Brother Oni]

That just means that superbugs are soon going to be able to resist that as well.

Still, though, the more things that a bacteria puts effort into resisting, the more limitations they'll have on functioning in other ways.

As Dodom pointed out, all the technical details are either missing or paywalled, so we can only speculate on the mechanism. If it works on a purely physical level, then it would be very difficult to develop resistance to it.

To use a reductio ad absurdum example, suppose you had a mixed-gender prison and shanked each of the prisoners. Let the ones that survive breed, then shank all the offspring once they've grown up enough. Theoretically, over enough generations, you should evolve stab-proof inmates, which is as ridiculous as it sounds.

The Discoworld series had an excellent example of this in Small Gods (I think) - eagles eat tortoises by carrying them up high and dropping them onto rocks to smash their shells open. This means that eventually, a tortoise will learn how to fly.

[Khedrac]

To use a reductio ad absurdum example, suppose you had a mixed-gender prison and shanked each of the prisoners. Let the ones that survive breed, then shank all the offspring once they've grown up enough. Theoretically, over enough generations, you should evolve stab-proof inmates, which is as ridiculous as it sounds.
Umm, no - probably.
The above is much closer to Lamarkism than Natural Selection as an evolutionary mechanism. This was disproved by showing that if you cut the tails of mice before allowing them to breed the tailes don't get any shorter.
A better method to allow Natural Selection to select for the ability to survive being stabbed would be to allow all the inmates to breed before you stab them, then only raise the offspring of the ones that survive the longest - and even that is very poor for a Natural Selection method.
You would need to ensure that all the stabbings are identical and you would probably eventually select for a mutaion that moved things around slightly - so the same stabbing would not hit vitals, but a slightly different one would still kill.

The other problem is that I seem to remember that they recently (last year or so) found an example of evolution that does appear to be on Lamark's principles and not Natural Selection...

[Grinner]

Umm, no - probably.
The above is much closer to Lamarkism than Natural Selection as an evolutionary mechanism. This was disproved by showing that if you cut the tails of mice before allowing them to breed the tailes don't get any shorter.
A better method to allow Natural Selection to select for the ability to survive being stabbed would be to allow all the inmates to breed before you stab them, then only raise the offspring of the ones that survive the longest - and even that is very poor for a Natural Selection method.

I disagree. Brother Oni's proposition doesn't rely on Lamarckian inheritance at all; it's pretty straightforward survival-of-the-fitteset.


You would need to ensure that all the stabbings are identical and you would probably eventually select for a mutaion that moved things around slightly - so the same stabbing would not hit vitals, but a slightly different one would still kill.

For that reason, randomized approaches would likely produce a better result.


The other problem is that I seem to remember that they recently (last year or so) found an example of evolution that does appear to be on Lamark's principles and not Natural Selection...

Epigenetics?

[Leewei]

Epigenetics?

You know, when I first heard of Epigenetics, that (Lamarck) is exactly what went through my head.

[Tyndmyr]

I wouldn't get my hopes too high just yet - things that work on mice and fail on humans are routine in medical testing, there's a lot of winnowing at every stage.

As XKCD once illustrated, whenever you hear "kills cancer", remember, so does a handgun. There's a lot of pieces that have to work out to make something a viable cure.

I'm more confident in multi-drug regimens. Us accruing more and more treatment options is great, but multi-drug treatments to reduce or remove resistance options, as well as different tiers of antibiotics should work pretty well. We could do better in encouraging proper antibiotics usage, but even so, superbugs are not really the unstoppable menace they're often portrayed as.