# New antibiotic that kills drug resistant bugs and is 'drug-resistant resistant' **URL:** \ **Category:** Miscellaneous and Personal Stuff I Must Share\ **Created:** [April 11, 2013, 7:53am UTC](https://boards.straightdope.com/t/new-antibiotic-that-kills-drug-resistant-bugs-and-is-drug-resistant-resistant/655385 "2013-04-11T07:53:12Z")\ **Posts on this page:** 15\ **Page:** 1
**Author:** ![deltasigma](https://avatars.discourse-cdn.com/v4/letter/d/e5b9ba/32.png) [@deltasigma](https://boards.straightdope.com/u/deltasigma)\ **Post date:** [April 11, 2013, 7:53am UTC](https://boards.straightdope.com/t/new-antibiotic-that-kills-drug-resistant-bugs-and-is-drug-resistant-resistant/655385/1 "2013-04-11T07:53:12Z")
Bullshit right? You have to read the [article](http://www.sciencedaily.com/releases/2013/04/130410201828.htm). The drug is called Epimerox. The approach is Machiavellian in its brilliance - especially since it gets someone (thing) else to do few million years of the hard work. Bacteria have enemies too. They’re viruses called phages. These tend to be specialized for infecting a specific class of bacteria. In this case they were interested in anthrax which apparently is in the same class as bugs like MRSA. The idea was that since these phages have been infecting the same types of bugs for millions of years, if the bacteria could mutated around being infected by now, they would have. So let’s see how the phages do it and see what we can learn. What they found was that it targets an enzyme (actually, specific docking sites on the protein structure) called 2-epimerase. > [@](#): > > Through the collaboration with Astex, initiated by co-author Allan Goldberg, an inhibitor of 2-epimerase named Epimerox was developed. Raymond Schuch, a former postdoctoral researcher in Fischetti’s lab, tested the inhibitor in mice infected with _Bacillus anthracis_. He found that not only did Epimerox protect the animals from anthrax, but the bacteria did not develop resistance to the inhibitor. The researchers also found that Epimerox was able to kill methicillin-resistant _Staphylococcus aureus_ (or MRSA) with no evidence of resistance even after extensive testing. Their work was published this week in _PLOS ONE_. > “Since nearly all Gram-positive bacteria contain 2-epimerase, we believe that Epimerox should be an effective broad-range antibiotic agent,” says Fischetti. “The long-term evolutionary interaction between phage and bacteria has allowed us to identify targets that bacteria cannot easily change or circumvent. That finding gives us confidence that the probability for developing resistance to Epimerox is rather low, thereby enabling treatment of infections caused by multi-drug-resistant bacteria such as MRSA. It is a very encouraging result at a time when antibiotic resistance is a major health concern.” ---
**Author:** ![Senegoid](https://sea3.discourse-cdn.com/straightdope/user_avatar/boards.straightdope.com/senegoid/32/6606_2.png) [@Senegoid](https://boards.straightdope.com/u/Senegoid)\ **Post date:** [April 11, 2013, 8:52am UTC](https://boards.straightdope.com/t/new-antibiotic-that-kills-drug-resistant-bugs-and-is-drug-resistant-resistant/655385/2 "2013-04-11T08:52:01Z")
Any mention of its side-effects or adverse effects on the test subjects? Did it kill them too? Or have any other apparent problems? ---
**Author:** ![deltasigma](https://avatars.discourse-cdn.com/v4/letter/d/e5b9ba/32.png) [@deltasigma](https://boards.straightdope.com/u/deltasigma)\ **Post date:** [April 11, 2013, 9:01am UTC](https://boards.straightdope.com/t/new-antibiotic-that-kills-drug-resistant-bugs-and-is-drug-resistant-resistant/655385/3 "2013-04-11T09:01:51Z")
The article mentions that the drug targets an allosteric site on the enzyme not present in humans so presumably the only issue would be if it happened to be a ligand for a critical site on some other human protein. But IDK. I’m sure there are probably a lot of other considerations too. edit: allosteric sites are ones that are not the active site of an enzyme. Ligands that bind to the active site tend to shut down activity. Binding to an allosteric site can modulate it. ---
**Author:** ![Lynn\_Bodoni](https://avatars.discourse-cdn.com/v4/letter/l/e47c2d/32.png) [@Lynn\_Bodoni](https://boards.straightdope.com/u/Lynn_Bodoni)\ **Post date:** [April 11, 2013, 9:52am UTC](https://boards.straightdope.com/t/new-antibiotic-that-kills-drug-resistant-bugs-and-is-drug-resistant-resistant/655385/4 "2013-04-11T09:52:15Z")
I’m allergic to half a dozen antibiotics, and I’ve had MRSA. This news makes me very happy. Not just for me, but for everyone. ---
**Author:** ![Gagundathar](https://avatars.discourse-cdn.com/v4/letter/g/a183cd/32.png) [@Gagundathar](https://boards.straightdope.com/u/Gagundathar)\ **Post date:** [April 11, 2013, 10:19am UTC](https://boards.straightdope.com/t/new-antibiotic-that-kills-drug-resistant-bugs-and-is-drug-resistant-resistant/655385/5 "2013-04-11T10:19:25Z")
This appears to be impressive work. I look forward to the clinical trials. ---
**Author:** ![lazybratsche](https://avatars.discourse-cdn.com/v4/letter/l/ba8739/32.png) [@lazybratsche](https://boards.straightdope.com/u/lazybratsche)\ **Post date:** [April 11, 2013, 12:14pm UTC](https://boards.straightdope.com/t/new-antibiotic-that-kills-drug-resistant-bugs-and-is-drug-resistant-resistant/655385/6 "2013-04-11T12:14:55Z")
Definitely cool. But be aware that there’s a humungous gap between initial promising results, the media hype, and having a drug that actually reaches FDA approval. That gap can be measured in 1% success rates and hundreds of millions of dollars. I’ve seen this sort of thing happen before: “the bacteria can’t possibly evolve resistance if we target _this_ protein!”. But they do, through some unanticipated mechanism. The target itself might not be able to mutate, but the bacteria has plenty of other potential ways to chew up and spit out any small molecules that might harm it. Full text is freely available here: > **[Use of a Bacteriophage Lysin to Identify a Novel Target for Antimicrobial...](https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0060754)** > > We identified an essential cell wall biosynthetic enzyme in Bacillus anthracis and an inhibitor thereof to which the organism did not spontaneously evolve measurable resistance. This work is based on the exquisite binding specificity of... ---
**Author:** ![Jackmannii](https://sea3.discourse-cdn.com/straightdope/user_avatar/boards.straightdope.com/jackmannii/32/311_2.png) [@Jackmannii](https://boards.straightdope.com/u/Jackmannii)\ **Post date:** [April 11, 2013, 12:59pm UTC](https://boards.straightdope.com/t/new-antibiotic-that-kills-drug-resistant-bugs-and-is-drug-resistant-resistant/655385/7 "2013-04-11T12:59:58Z")
> [@lazybratsche](#): > > Definitely cool. But be aware that there’s a humungous gap between initial promising results, the media hype, and having a drug that actually reaches FDA approval. That gap can be measured in 1% success rates and hundreds of millions of dollars. I’ve seen this sort of thing happen before: “the bacteria can’t possibly evolve resistance if we target _this_ protein!”. But they do, through some unanticipated mechanism. The target itself might not be able to mutate, but the bacteria has plenty of other potential ways to chew up and spit out any small molecules that might harm it. Yes, this unfortunately. It’d be nice if we could End Resistance As We Know It, but we won’t know it in this instance for years (even if the drug passes clinical trials). You’re always trying to stay a jump ahead of the pathogens, but they have other ideas. ---
**Author:** ![Cheesesteak](https://sea3.discourse-cdn.com/straightdope/user_avatar/boards.straightdope.com/cheesesteak/32/3694_2.png) [@Cheesesteak](https://boards.straightdope.com/u/Cheesesteak)\ **Post date:** [April 11, 2013, 1:38pm UTC](https://boards.straightdope.com/t/new-antibiotic-that-kills-drug-resistant-bugs-and-is-drug-resistant-resistant/655385/8 "2013-04-11T13:38:32Z")
OTOH, targeting aspects of the pathogen that have already been proven resistant to… resistance is a clever way around the problem. If bacteria could develop resistance to phages, they would have done it already. Unless, of course, the phages change continually as well, which they may be. You can make weeds that are resistant to glyphosate by using it over and over. You’re not likely to make weeds resistant to pulling them out of the ground and burning them in a barrel by doing that over and over. ---
**Author:** ![gotpasswords](https://avatars.discourse-cdn.com/v4/letter/g/c57346/32.png) [@gotpasswords](https://boards.straightdope.com/u/gotpasswords)\ **Post date:** [April 11, 2013, 2:16pm UTC](https://boards.straightdope.com/t/new-antibiotic-that-kills-drug-resistant-bugs-and-is-drug-resistant-resistant/655385/9 "2013-04-11T14:16:42Z")
[QUOTE=Cheesesteak] You can make weeds that are resistant to glyphosate by using it over and over. You’re not likely to make weeds resistant to pulling them out of the ground and burning them in a barrel by doing that over and over. [/QUOTE] Ever hear of thorns? 😃 And burning stuff like poison ivy is rather bad idea. There are enough mopes out there who go to the doc with sniffles and demand antibiotics, that any developments in drug resistance-proof antibiotics are encouraging. ---
**Author:** ![Smeghead](https://avatars.discourse-cdn.com/v4/letter/s/f1d935/32.png) [@Smeghead](https://boards.straightdope.com/u/Smeghead)\ **Post date:** [April 11, 2013, 2:39pm UTC](https://boards.straightdope.com/t/new-antibiotic-that-kills-drug-resistant-bugs-and-is-drug-resistant-resistant/655385/10 "2013-04-11T14:39:39Z")
> [@Cheesesteak](#): > > OTOH, targeting aspects of the pathogen that have already been proven resistant to… resistance is a clever way around the problem. If bacteria could develop resistance to phages, they would have done it already. Unless, of course, the phages change continually as well, which they may be. This was my first thought as well. I didn’t read the article - did they measure the rate of evolution of this protein in the bacteria and the corresponding protein in the phages? I’d be very surprised to find that they’ve been static over evolutionary time. ---
**Author:** ![Boyo\_Jim](https://avatars.discourse-cdn.com/v4/letter/b/87869e/32.png) [@Boyo\_Jim](https://boards.straightdope.com/u/Boyo_Jim)\ **Post date:** [April 11, 2013, 5:55pm UTC](https://boards.straightdope.com/t/new-antibiotic-that-kills-drug-resistant-bugs-and-is-drug-resistant-resistant/655385/11 "2013-04-11T17:55:57Z")
Resistance is futile. ---
**Author:** ![Pai325](https://avatars.discourse-cdn.com/v4/letter/p/c68b51/32.png) [@Pai325](https://boards.straightdope.com/u/Pai325)\ **Post date:** [April 11, 2013, 10:19pm UTC](https://boards.straightdope.com/t/new-antibiotic-that-kills-drug-resistant-bugs-and-is-drug-resistant-resistant/655385/12 "2013-04-11T22:19:55Z")
> [@Lynn\_Bodoni](#): > > I’m allergic to half a dozen antibiotics, and I’ve had MRSA. This news makes me very happy. Not just for me, but for everyone. I’m allergic to many common antibiotics, too. Bet I’m allergic to this. Guess you can tell I’m a glass half empty person. ---
**Author:** ![aruvqan](https://sea3.discourse-cdn.com/straightdope/user_avatar/boards.straightdope.com/aruvqan/32/2891_2.png) [@aruvqan](https://boards.straightdope.com/u/aruvqan)\ **Post date:** [April 11, 2013, 11:26pm UTC](https://boards.straightdope.com/t/new-antibiotic-that-kills-drug-resistant-bugs-and-is-drug-resistant-resistant/655385/13 "2013-04-11T23:26:08Z")
> [@Pai325](#): > > I’m allergic to many common antibiotics, too. > > Bet I’m allergic to this. > > Guess you can tell I’m a glass half empty person. ROFLMAO I am also allergic to many antibiotics, though I am hoping I can use this one. I prefer my glass to be half full [or nick your glass …😛] ---
**Author:** ![lazybratsche](https://avatars.discourse-cdn.com/v4/letter/l/ba8739/32.png) [@lazybratsche](https://boards.straightdope.com/u/lazybratsche)\ **Post date:** [April 12, 2013, 12:18pm UTC](https://boards.straightdope.com/t/new-antibiotic-that-kills-drug-resistant-bugs-and-is-drug-resistant-resistant/655385/14 "2013-04-12T12:18:01Z")
> [@Cheesesteak](#): > > OTOH, targeting aspects of the pathogen that have already been proven resistant to… resistance is a clever way around the problem. If bacteria could develop resistance to phages, they would have done it already. Unless, of course, the phages change continually as well, which they may be. > > You can make weeds that are resistant to glyphosate by using it over and over. You’re not likely to make weeds resistant to pulling them out of the ground and burning them in a barrel by doing that over and over. It’s a clever approach, but targeting a particular bacterial enzyme that can’t mutate does not preclude resistance. The bacteria can still evolve a way to metabolize, sequester, or export the new antibiotic. That’s how bacteria resist lots of antibiotics. Penicillin, for example, binds to enzymes that build the bacterial cell wall (similar to this new enzyme in fact). Resistant bacteria produce an enzyme, beta-lactamase, that chews up penicillin (and the whole class of similar antibiotics). But as far as I know bacteria do not evolve resistance by mutating the target of penicillin. At first glance, the antibiotic in this study seems like it could be very easily metabolized by bacteria. One of its chemical groups is a common amino acid (phenylalanine). Though I’d WAG that the pharmaceutical company involved in this research is probably keeping their best candidate drugs secret for now, and just published this as a proof of concept with their least plausible candidate that had a useful effect. > [@Smeghead](#): > > This was my first thought as well. I didn’t read the article - did they measure the rate of evolution of this protein in the bacteria and the corresponding protein in the phages? I’d be very surprised to find that they’ve been static over evolutionary time. They don’t go that far, no. All they do in this study is observe that a flask full of bacteria doesn’t contain any that are spontaneously resistant to the new antibiotic (whereas you find a few that are resistant to other classes of antibiotic). A previous study I glanced over went a little further, and found that mutagenized bacteria didn’t become resistant to the phage lysin. (If I put on my “science snob” hat, I have to wonder why they published in PLOS One. That’s a journal for results that aren’t sexy or interesting enough to publish elsewhere (not that there’s anything wrong with that). My gut feeling is that they could have published this in a much higher-prestige microbiology or pharmacology journal if there was much merit to this approach.) ---
**Author:** ![Mangetout](https://sea3.discourse-cdn.com/straightdope/user_avatar/boards.straightdope.com/mangetout/32/19_2.png) [@Mangetout](https://boards.straightdope.com/u/Mangetout)\ **Post date:** [April 12, 2013, 12:43pm UTC](https://boards.straightdope.com/t/new-antibiotic-that-kills-drug-resistant-bugs-and-is-drug-resistant-resistant/655385/15 "2013-04-12T12:43:07Z")
Even if there is a way for bacteria to develop resistance to something like this, it’s still good news (I mean, assuming it can be made into a workable medicine), because it puts us ahead in the arms race against bacteria, even if only for a while.