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Biotech Medicine

Researchers Find "Achilles Heel" of Drug Resistant Bacteria 106

Rambo Tribble writes Researchers in Britain are reporting that they have found a way to prevent bacteria from forming the "wall" that prevents antibiotics from attacking them. “It is a very significant breakthrough,” said Professor Changjiang Dong, from the University of East Anglia's (UAE) Norwich Medical School. “This is really important because drug-resistant bacteria is a global health problem. Many current antibiotics are becoming useless, causing hundreds of thousands of deaths each year. Many bacteria build up an outer defence which is important for their survival and drug resistance. We have found a way to stop that happening," he added. This research provides the platform for urgently-needed new generation drugs.
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Researchers Find "Achilles Heel" of Drug Resistant Bacteria

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  • E. Coli and salmonella are not caused by the same "bug".
    • by theshowmecanuck ( 703852 ) on Friday June 20, 2014 @01:54AM (#47279295) Journal
      They are talking about the class of bacteria that can form the barrier they mention. That is, "Gram-negative bacteria" [wikipedia.org] which includes "Escherichia coli (E. coli), Salmonella, Shigella, and other Enterobacteriaceae, Pseudomonas, Moraxella, Helicobacter, Stenotrophomonas, Bdellovibrio, acetic acid bacteria, Legionella etc.". (Courtesy of Wikipedia)
      • The article also uses MRSA, which is gram positive, as their prime example of resistant bacteria.

        • by MrBingoBoingo ( 3481277 ) on Friday June 20, 2014 @02:48AM (#47279435) Homepage
          The mention of MRSA in the article was probably erroneous and sloppy reporting. Gram Negative bacteria tend to resist chemotherapy due to robust cell walls. Gram Positive bacteria like MRSA, VRSA, VRE, et al... resist drug therapy by other means. This covers nothing of the most concerning drug resistant bacteria, but merely offers a way to make some bacteria vulnerable to drugs that they were not vulnerable to before.
          • by dfm3 ( 830843 ) on Friday June 20, 2014 @08:32AM (#47280443) Journal
            As a microbiologist, I agree that the Telegraph article is rife with errors. The original article is paywalled, but from the abstract it sounds as if the researchers described a mechanism by which lipopolysaccharide, a component of the gram-negative cell wall which provides some degree of antibiotic resistance, is exported from the cell. I understand Dong, et al to be suggesting that a compound which prevents proper transport of LPS could be used synergistically with another drug which would otherwise be blocked from entry into the cell by LPS.

            Further, the use of the term "immunity" to describe antibiotic resistance is a pet peeve of mine, as these terms do not mean the same thing!
            • What are you doing around here? I thought all original, intelligent, knowledgeable commenters had left /.?
            • by Anonymous Coward

              Blocking LPS trasnsport is fatal to Gram-negative bacteria. As this protein is on the surface it can be targeted without a drug having to enter the cell (and hence avoiding most antibiotic resistance methods). There are already very effective small peptide-like compounds that insert directly into the membrane, bind to the pore and block the transport. This structure (and the other one published in the same issue of Nature) give a model to base further development on.

  • Or their enchanted shin.
    • I read that as enchanted skin, which would have been entirely appropriate for Achilles, as well. And that's what we don't have when we use a bunch of funky cleaners on our skin, removing its natural acidity. Even our washing habits impinge on our body's ability to protect itself.

      • I read that as enchanted skin, which would have been entirely appropriate for Achilles, as well. And that's what we don't have when we use a bunch of funky cleaners on our skin, removing its natural acidity. Even our washing habits impinge on our body's ability to protect itself.

        I rather deal with bacteria than with rancid-smelly people. YMMV :)

  • HOPE to exploit it (Score:5, Informative)

    by kae77 ( 1006997 ) on Friday June 20, 2014 @01:44AM (#47279267)

    From TFA ... researchers have discovered what causes anti-biotic resistance, and HOPE to use that to discover how to stop them from becoming resistant.

    The summary suggests that they already have. The summary will be perfect in "a few years time" when the researchers hope to have the solution.

    • by Bob_Who ( 926234 )

      The summary will be perfect in "a few years time" when the researchers hope to have the solution.

      So this is less a news story and more a fund raising effort. That rings true to me. I think we're seeing a lot more advertisement built right into the programming these days... What a novel idea: sell a lot of snake oil to sick people.

      • Re: (Score:3, Insightful)

        by Anonymous Coward

        Well they did make a discovery. What do you suggest? That science not raise funds for continued research? Nothing was mentioned in the article to send them money btw. Money is needed for science, those who make advances should get it.

    • More importantly, is this something fundamental to how gram-negative bacteria develop, or is it simply the current solution evolution has produced ? It would be nice to develop biotechnology that takes evolution into account and is ready to predict a few moves ahead and minimize the probability of a helpful mutation.

      It seems to me that from a computer security point of view, the human biological computer has low entropy keys and we are dealing with a massively parallel adversary that tries trillions of keys

  • by El Puerco Loco ( 31491 ) on Friday June 20, 2014 @01:50AM (#47279285)

    Does this only work on bacteria that are pretending to be gram-negative? It's like the menu from the pizza place in my neighborhood that uses quotes around words like "chicken." What are they really serving?

  • Easier (Score:2, Insightful)

    by Hamsterdan ( 815291 )

    Stop disinfecting and over-cleaning everything. Remove the Purell crap. Let kids eat dirt.

    1- It will force people to build their immune system (I'm not always sick like younger generations)
    2- If you stop killing 99.999% of all bacteria, it will put an end to super-bacteria (the 0.0001% that survive and reproduce)

    I *never* use any kind of medicine (unless I have no choice), I never use band aids on nicks and scratches (don't disinfect them either). I have no food intolerance, food allergies or other weird ai

    • Re:Easier (Score:5, Informative)

      by rsmith-mac ( 639075 ) on Friday June 20, 2014 @03:02AM (#47279473)

      Stop disinfecting and over-cleaning everything. Remove the Purell crap

      Purell is alcohol based (good ole' ethanol). That has nothing to do with antibiotics and the antibiotic resistant bacteria in TFA.

      • Re:Easier (Score:5, Interesting)

        by Rei ( 128717 ) on Friday June 20, 2014 @04:56AM (#47279801) Homepage

        Yeah, not everything is practical to develop resistance to. I mean, you're not going to have bacteria developing resistance to, say, a flame thrower ;) Even yeast, who make the stuff, get killed by alcohol when it's in too strong of a concentration. Don't get me wrong, there are alcohol-resistant bacteria. But we're not talking about a surface protein difference here or anything, we're talking "entirely spored off to stop the alcohol from dissolving the cell membrane". To resist alcohol the cell has to be so encased that it can't do anything else but wait for the alcohol to go away. And it has to be so encased at the time of exposure, not afterwards.

        Alcohol-resistant species, most notably Clostridium, can be a problem for people who are sterilizing equipment. But these aren't species that developed alcohol resistance in response to doctors, these are naturally spore-forming species. Alcohol is such a brute force attack, a simple tweak to a cell just doesn't cut it. And alcohol has been a threat to microbes for a long, long time. And even if some species did develop an alcohol resistance and began to pose a threat, that would only have significance to people sterilizing equipment / surfaces. It wouldn't make a difference in terms of how to treat an infection once its in the body; it's not like you're not going to replace your blood with 90% isopropyl alcohol. ;)

        • by Anonymous Coward

          I mean, you're not going to have bacteria developing resistance to, say, a flame thrower

          They worked hard at it though:
          https://en.wikipedia.org/wiki/Pyrolobus_fumarii

          • by kesuki ( 321456 )

            yes hydrothermal life can resist an autoclave but... "However, Strain 121 is non-infectious because it cannot grow at temperatures near 37 ÂC.[citation needed]"http://en.wikipedia.org/wiki/Strain_121 [wikipedia.org]
            also flame throwers are considerably hotter than an autoclave, but they might be able to grow again after being flame thrown we won't know til someone tests it out.

        • ...it's not like you're not going to replace your blood with 90% isopropyl alcohol. ;)

          Challenge accepted. *grabs bourbon*

        • it's not like you're not going to replace your blood with 90% isopropyl alcohol.

          God no, that'd give you the mother of all hangovers.

      • by Anonymous Coward

        Purell is alcohol based (good ole' ethanol). That has nothing to do with antibiotics and the antibiotic resistant bacteria in TFA.

        Parent was trying to advocate sterilizing less to keep an active immune system that is always seeing new things. The belief is that if you over sterilize, the immune system not only becomes less responsive but didn't develop immunity to low dose pathogens when it is less risky. Parent was not trying to say that Purell is responsible for antibiotic resistant bacteria in any form

    • Re: (Score:3, Insightful)

      by Anonymous Coward

      I never use band aids on nicks and scratches (don't disinfect them either)

      I didn't once, and I ended up in hospital on a drip with an infection in my finger.

      I'm not always sick like so many others, either.

      Random chance has a bit to do with it.

      • Re: (Score:2, Insightful)

        by Anonymous Coward

        There's a reason average life expectancy used to be 35 years.

        • The Reason... (Score:3, Interesting)

          The reason average life expectancy has more than doubled in a century or two is that infant mortality has been reduced, bringing the average up.

          There is not so much difference in survival expectancy once on is an adult.

          • Re:The Reason... (Score:5, Informative)

            by Overzeetop ( 214511 ) on Friday June 20, 2014 @06:49AM (#47280077) Journal

            Yeah, don't think so. I suggest this chart: http://www.infoplease.com/ipa/... [infoplease.com]

            The age of mortality for non-infants (those living past age 10) has increased by 20-25 years, a 50% increase in life expectancy, in the past century. Even if you look at "adults", or those who make it to age 20, there is still a 17-23 year increase. Again, a 50% increase in longevity for adults.

            • Why the percentages? In real terms life expectancy from adulthood (20+) increased 17-22 years while the infant (0) life expectancy has increased by 37-40 years. According to the chart you referenced.

              • Well, the whole discussion centered around is a ratio (doubling, a 100% increase). If you want to compare the veracity, you should use similar scales. 17-22 years means nothing unless you put it into the same context.

          • This must be why doctors tell you to fuck right off if you're over 18 and you stagger into a hospital with a severed arm tucked under the unsevered one.

            Because if they stop the bleeding, reattach it, give you a transfusion & antibiotics you're precisely as likely to survive as if they dripped holy water on your head and chopped the other one off.

          • The increased life expectancy probably has a lot more to do with widespread adoption of domestic refrigeration technology 75-100 years ago than sterilization techniques.
        • by alen ( 225700 )

          not in biblical times, back then it was like 900 years

    • by Bob_Who ( 926234 )

      I *never* use any kind of medicine (unless I have no choice), I never use band aids on nicks and scratches (don't disinfect them either). I have no food intolerance, food allergies or other weird ailment.

      You must be descended from wild men with stone tools who lived in caves and ate mastodon meat with the Flintstones. I think we're related.

    • by Anonymous Coward

      This. And more so in farm settings.

      Farms need to build upwards instead of trying to force so many animals in to a flat horizontal space.
      It is abusive, it is inefficient and just leads to abuse of antibiotics out the ass as a preventative measure.

      The only place that needs to be regularly cleaned is spaces around babies, hospitals and old people.
      Average population doesn't need any of that and it is abusive to allow it.
      All these stupid gels and such for your plates and kitchens aren't helping either. (the AB

      • The only place that needs to be regularly cleaned is spaces around babies, hospitals and old people.

        Nice try kid. Now go and clean up your room.

    • Right, because fewer people died of opportunistic infections before we had anti biotics and disinfectants.

    • Re:Easier (Score:5, Interesting)

      by duke_cheetah2003 ( 862933 ) on Friday June 20, 2014 @07:28AM (#47280181) Homepage

      Stop disinfecting and over-cleaning everything. Remove the Purell crap. Let kids eat dirt.

      1- It will force people to build their immune system (I'm not always sick like younger generations)
      2- If you stop killing 99.999% of all bacteria, it will put an end to super-bacteria (the 0.0001% that survive and reproduce)

      I *never* use any kind of medicine (unless I have no choice), I never use band aids on nicks and scratches (don't disinfect them either). I have no food intolerance, food allergies or other weird ailment.

      Not to burst your bubble, and not really saying these are bad ideas, I infact condone this. Buuut... killing bacteria, being cleanly does not create drug-resistant bacteria. People not finishing their meds after they feel better is what creates nasty bugs, along with a good dose of over prescribing antibiotics. But washing your hands with a disinfectant has little to nothing to do with this problem. They're not becoming resistant to our germ killing soaps and lotions... it's the medications once the bugs get inside you that they're getting good at protecting themselves against.

      • Re: (Score:2, Insightful)

        by Anonymous Coward

        You're missing the really troublesome one: low-level antibiotic use in livestock. As a society, it's cheaper to not treat sick animals. Just keep them out of human food, turn them into pet food. Cats and dogs are much more capable of dealing with the meat of sick animals. That's a predator thing, their predecessors have been hunting sick animals for millions of years. of course, what's profitable to society isn't always profitable to farmers. They'll make more money by using antibiotics and butchering the s

        • by gewalker ( 57809 )

          Actually, the real problem is not treating sick livestock. It is using antibiotic simply to make them fatten more quickly and this practice is very widespread.

          • by sudon't ( 580652 )

            Yes, this. I have long thought that the DEA's focus should be turned away from recreational drugs, and towards antibiotics. Antibiotic abuse, (mostly by factory farming operations), is a very real threat to society, unlike recreational drug use, plus, the drug warriors wouldn't have to fight legalization out of fear of losing their jobs.

            And yes, we need to reduce our germophobia, as well.

        • Oh, our predecessors weren't preying on sick animals for millions of years, just cats and dogs?

      • It is complex but antibacterial soaps do make the problem worse.

        The first line of defense your body has against foreign bacteria is not your immune system it is your own bacteria. When you wipe out them you create vulnerabilities in the system. Most antibiotic strains of bacteria don't survive very well compared to the non-antibiotic strains if no antibiotics are present. The same is true for many other resistance.

        What this means is don't take things to an extreme. After you go to the bathroom you should wa

        • After you go to the bathroom you should wash your hands and if you get a cut you should clean it and seal it.

          Meh. I just lick my hands/cut. Since it's my own body, how much can it hurt me?*

          * Joking (partially). I generally don't cover small scrapes and scratches and yes, I do lick my wounds, but yes, I do wash my hands.**

          ** Stated for those who don't grasp sarcasm/kidding.
      • Except washing your hands with antibiotic soap is introducing low levels of that antibiotic downstream from your sink. Into places where bacteria thrive, and compete with each other. Bacteria that develop antibiotic resistance in that environment are healthier and better able to compete.

        Unless you are boiling your gray water after washing up with antibiotic soap, you ARE contributing to the increase in low dose antibiotics in the greater ecosystem, and that is definitely a part of the problem.

        • by tibit ( 1762298 )

          There's no such thing as antibiotic soap. There is antibacterial soap. Those are very different things. The antibacterial compounds can't be and aren't taken internally and have nothing to do with antibiotics.

      • by dgatwood ( 11270 )

        They're not becoming resistant to our germ killing soaps and lotions...

        Actually, they are. Resistance to triclosan (one of the more popular germ killing agents used in soaps and lotions) is on the rise. The triclosan-resistant MRSA strains are particularly disconcerting, as they make disinfection in hospitals a lot harder. And given that the epidermal varieties of staph are showing increaed triclosan resistance while S. aureus (which is mostly found inside the body) isn't, there's little question at this

        • by Reziac ( 43301 ) *

          This is when I need an anti-microbial to use on surfaces, I use straight undiluted 6% bleach. From what I've read, since it pretty much dissolves microbes, there is no resistance.

          • by dgatwood ( 11270 )

            Except that bleach resistance is starting to show up in cholera [nih.gov].

            Yikes.

            • by Reziac ( 43301 ) *

              'Course, we've only recently had to tools to investigate and identify it...

              Also this obsession with "only use enough to do the job" -- er, no. That is what selects for resistance, by killing all the weaker individuals but leaving the strongest alive. If you're going to treat, do so at a level that kills ALL of the target species.

              In my application, I'm most interested in killing off parvovirus (a really tough virus, resistant to a lot of common chemicals, but reliably killed by bleach) and coccidia (another

      • " People not finishing their meds after they feel better is what creates nasty bugs"

        Agree, but then again, unless you kill 100% of the critters, the 0.001% that survives (and is immune to that antibiotic) will reproduce and create a strain that is resistant to that same antibiotic...

    • Re:Easier (Score:5, Interesting)

      by k8to ( 9046 ) on Friday June 20, 2014 @07:43AM (#47280243) Homepage

      I'm a medical minimalist, but refusing to sterilize cuts is kind of stupid.

      Your immune system doesn't need a significant exposure to antigens to trigger the normal hypothalamus reactions and induce immune-system learning and memory reactions. Meanwhile your immune system isn't guaranteed to win arbitrary scale battles and you don't really know what was on whatever cut you. It's not like really unfortunate bacteria are all that rare.

      You should also realize that you get away with this because you live in a relatively low-bacteria environment, such as an arid or temperate one. By your logic you should move to the tropics because you'll get far more exposure to diseases. Only there refusing to sterelize cuts will lead to some really bad situations.

    • I completely agree; we need sane preventitive health measures to become a priority. It is well known that this is also where the most is to be gained. However - antibiotics are still nice to have for those very extreme and nasty cases. I just hope we start learning to use them only when they are really needed.
    • So, you prove you are lucky. Nothing else. I smoke 20 cigarettes a day I am 37 and have no cancer. So smoke 20 cigarettes a day until 37. You are safe.
    • While some of what you are saying is reasonable and makes sense, you are about 1% away from being an anti-vaxer.

      You don't clean your wounds? Ok, you are pretty much on their level. Enjoy your Teatnus. [wikipedia.org]

    • Remove the Purell crap.

      Oh, come on! Purell is a good fire starting gel.

  • Whatever happened to the idea of using bacteriophage's? Against e-coli http://www.cellsalive.com/phage.htm or more generally http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3278644/ . Wasn't this the hot new way to fight superbugs? And the research mentioned is nothing more than a study of the creation methodology of the bacterias method of shielding itself, it doesn't even mention an actual counter or potential chemical cocktail to hit the infection with . Certainly it's a nice advancement but it's not a cure

    • Whatever happened to the idea of using bacteriophage's?

      Nobody knew which thing that belonged to a bacteriophage they were supposed to use.

  • Call me pedantic, but... It's the University of East Anglia (UEA), not the United Arab Emirates (UAE).
  • by Anonymous Coward

    One of the main mechanisms for antibiotic resistance is efflux pumping. Drug makes it across the membrane and then is pumped out before it can reach a lethal concentration. If you can attack the cell from outside then you can sidestep this mechanism.

    There are a natural class of antimicrobials called Protegrins that usually insert into the membrane from outside and combine to form a pore, spilling the cell contents. If you modify these you can make them lethal without forming a pore and in this state the pro

  • So once we create new antibiotics that can defeat these types of drug-resistant bacteria, how long will it be until a completely new resistance appears? Let's hope that in the next century our ability to engineer new antibiotics exceeds the pace that bacteria can evolve to evade them.

    • by Anonymous Coward

      "So once we create new antibiotics that can defeat these types of drug-resistant bacteria, how long will it be until a completely new resistance appears?"

      In other words the bacteria found a way to erect a wooden door to keep off the drugs we used to kill them (so they survive) and now we found the way to weaken that wooden door and allow the drugs to go inside and kill them and you are saying that the bugs may choose to erect a steel door next time, and start the war anew?

    • FTFA This wouldn't be an antibiotic, and it seems to happen outside the cell's defensive mechanisms that they can inherit.

      • No, the outer membrane IS a genetic component, with many of the parts synthesized in the cell and transported outside to create the wall. The mechanism for doing this is partially elicited by the fine researchers. But the wall is coded by the critters genome.

        And. no, none of this is an actual antibiotic. The breathless hyperbole in TFA is the product of too much caffeine and too little attention in the 'ol classroom. The research points to targets that the putative antibiotic can exploit. Given the abi

    • So once we create new antibiotics that can defeat these types of drug-resistant bacteria, how long will it be until a completely new resistance appears? Let's hope that in the next century our ability to engineer new antibiotics exceeds the pace that bacteria can evolve to evade them.

      Nature is pretty astonishing, huh? In just 100 years, we've gone from finding antibiotics to bugs being able to defeat them. A blink of an eye in the scope of human history. I'm with ya, will it take another 100 years, or less for these bugs to evolve to resist whatever methods we discover to defeat them? I think it'll have a lot to do with what we've do with what we've learned this time. That being, we've learned that resistant bugs are completely our own darn fault.

      At least for now, we're keeping up

      • On the other hand, we have managed to totally defeat smallpox, rinderpest, and if we play our cards right, polio will soon join those ranks.
      • we'll win this arms race, because we're getting smarter and their just staying the same.

        it didn't take us very long to find something to kill them in the first place... once we knew they were there, 200 odd years.

        and in the last hundred look how fucking far we've come.

        • The most likely way we will 'win' this arms race is when we figure out how to fine tune the balance between pathogenic and commensal behavior. Right now, we're tossing grenades at mosquitoes. Works to some extent but there is significant collateral damage.

          We may get there - we've come a long way in understanding the complexities of the immune system and the molecular biology of bacteria.

          Now, if we could only pronounce and pay for the things scientists are developing, things could be golden.

      • At least for now, we're keeping up with them

        Over the commercial lifespan of 2000/XP, the cost of gene sequencing went down by five orders of magnitude (100,000 x) and there's still one more order of magnitude crumbling in full swing ($1b per human genome to $1000 per per human genome).

        We're not merely drinking their milkshake, we're reading their source code, and it's gone from the Manhattan project garage to hamburgers served in the length of time it takes for a helpless human baby to mature into a helples

    • by gewalker ( 57809 )

      There are evolutionary limits on how much bacteria (or other disease agents) can change. By the time you knock out the "low-hanging fruit" for possible resistance mechanisms, it is entirely possible that humans win in the war long-term. Assuming of course we don't lose the war in the short-term.

    • by Reziac ( 43301 ) *

      Well, in this case that's kinda like asking "How long before humans evolve a mechanism to prevent 'em from bleeding out if someone cuts their throat?" It's basically putting a hole in the bacteria's skin.

  • These grand announcements have a tendency to not pan out in 99% of the cases...

  • Bacteria have feet?
    Maybe the researchers aren't so drug resistant.
  • I told them to dip the bacteria in Iron Maiden, and not Styx. The heel vulerability was totally preventable.
  • In the article, Haohao Dong, another member of the UAE team, said: "Because new drugs will not need to enter the bacteria itself, we hope that the bacteria will not be able to develop drug resistance in future.".
    BS! Evolution teaches us that a members of the species that mutates into a species with a more effective wall, it will have beter survival rates and thus will have developed a resistance to these new drugs. So while wonderful that a new type of drug has been found, the overuse of antibiotics still n

  • Yeah I've had some of these so-called new Drugs like Antibiotics and such and the side-effects are worse than the disease. A lot of people including myself are unable to take some of the newer things like Avelox and Levaquin without turning yellow and having Heart palpitations. I think Aspirin and Penicillin were the last breakthroughs that gave the best performance with little to no side-effects for most people.

    Better testing and more focus on eradication of side-effects is what's really needed for any new

    • Sorry, both aspirin and the penicillins cause significant harm. In part because of the large quantity of the drugs that are used, they are relatively safe but even a drug with a good safety profile will cause problems if used often enough.

      TANSTAAFL.

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