# The antibiotic apocalypse - how scared should we be? **URL:** \ **Category:** Factual Questions\ **Created:** [February 3, 2013, 12:02am UTC](https://boards.straightdope.com/t/the-antibiotic-apocalypse-how-scared-should-we-be/649164 "2013-02-03T00:02:20Z")\ **Posts on this page:** 20\ **Page:** 3
**Author:** ![deltasigma](https://avatars.discourse-cdn.com/v4/letter/d/e5b9ba/32.png) [@deltasigma](https://boards.straightdope.com/u/deltasigma)\ **Post date:** [February 4, 2013, 11:27pm UTC](https://boards.straightdope.com/t/the-antibiotic-apocalypse-how-scared-should-we-be/649164/41 "2013-02-04T23:27:42Z")
> [@DSeid](#): > > The frog’s peptides are just one example of the already referenced innate immune system. Innate mechanisms work pretty well; the problem is that they are often fairly nonspecific. It’s enough that one’s innate system is able to attack only bacteria; differentiating between bacteria you need and pathogenic ones is a whole 'nuther thing. In general innate mechanisms therefore location specific. Hence not great as systemic antibiotics. > > Bacteria adapting to innate mechanisms is more difficult but generally not impossible. Change to charge of exposed bits of the cell wall and suddenly this one does not work any more. Can’t say I know how a bacteria would do that but I have great confidence that among the trillions and trillions of them out there, multiplying, multiplying, one would. Bacteria can adapt to virtually anything with enough consistent evolutionary pressure brought to bear. You’re talking about how an individual peptide targets the phospholipid layer of a bacterium and different peptides have different targeting techniques for just that reason - at least that what I’ve gleaned so far but if you can go into more depth I would be interested. That however wasn’t my point. My point was that bacteria aren’t going to develop immunity to having their cell walls punctured or chemically disrupted. Certainly being able to target the membrane in the first place is a prerequisite, but even if we want to argue that point, it’s going to depend on what we engineer the peptides to target. I mean I think we might be able to do a little better than the frogs in designing these things. ---
**Author:** ![DSeid](https://sea3.discourse-cdn.com/straightdope/user_avatar/boards.straightdope.com/dseid/32/20194_2.png) [@DSeid](https://boards.straightdope.com/u/DSeid)\ **Post date:** [February 5, 2013, 3:54am UTC](https://boards.straightdope.com/t/the-antibiotic-apocalypse-how-scared-should-we-be/649164/42 "2013-02-05T03:54:07Z")
I am talking about the very bit you quoted – about how these peptides target bacteria as a class over animal cells because bacterial membranes are negatively charged while animal cells are positively charged. Other antibiotics do that as well. [Yet](http://researchnews.osu.edu/archive/resistance.htm) it turns out bacteria already _have_ ways to change their charge (and targeting the means of doing so is one approach at limiting antibiotic resistance). > [@](#): > > Scientists have already observed that the cell membranes of many disease-causing bacteria develop resistance by changing their electrical charge from negative to positive. Many antibiotics work because they carry a positive charge that attracts them to negatively charged bacteria cells. The opposite charges allow antibiotics to penetrate and kill bacteria. But by changing their naturally occurring negative charge to positive, some bacteria cells establish a protective “coat” that repels the antibiotic. It can only punch through that which it binds to. Frogs have been at it for millions of years; I am not so sure we _can_ do any better than them. Meanwhile some good news. In Peds we’ve been vaccinating against the bacteria Pneumococcus since 2001 and have also come up with guidelines that advised sticking with plain old Amox but using it in a higher dose range, reserving other meds for treatment failures. [The result](http://www.metroatlantaotolaryngology.org/journal/sept08/Sinusitis%20after%20pneumovax.pdf) has not only been fewer persistent otitis media episodes and fewer treatment failures in kids, but a herd immunity effect on adults with fewer invasive disease cases in adults. FWIW. ---
**Author:** ![deltasigma](https://avatars.discourse-cdn.com/v4/letter/d/e5b9ba/32.png) [@deltasigma](https://boards.straightdope.com/u/deltasigma)\ **Post date:** [February 5, 2013, 4:08am UTC](https://boards.straightdope.com/t/the-antibiotic-apocalypse-how-scared-should-we-be/649164/43 "2013-02-05T04:08:31Z")
> [@DSeid](#): > > It can only punch through that which it binds to. I think I already made that observation and mentioned that wasn’t my main point. :dubious: ---
**Author:** ![DSeid](https://sea3.discourse-cdn.com/straightdope/user_avatar/boards.straightdope.com/dseid/32/20194_2.png) [@DSeid](https://boards.straightdope.com/u/DSeid)\ **Post date:** [February 5, 2013, 11:25am UTC](https://boards.straightdope.com/t/the-antibiotic-apocalypse-how-scared-should-we-be/649164/44 "2013-02-05T11:25:24Z")
I am sorry then. I don’t get your point. I thought the issue was bacteria potentially developing resistance to these particular peptides and the claim that such “cannot happen.” Resistance occurs in many ways. Amoxicillin works by preventing cell wall synthesis (thus similarly disrupting cell walls). Bacteria have not developed a way to avoid having cell wall synthesis disrupted no longer kill them. They instead produce something that destroys Amoxicillin. Augmentin (the souped up response to that) works by adding in something to suck up that enzyme, restoring Amoxicillin to more effective potency. Would your point be that then there is not really any Amox resistance? I am not meaning to come off snarky, I really am not getting what your main point is. ---
**Author:** ![deltasigma](https://avatars.discourse-cdn.com/v4/letter/d/e5b9ba/32.png) [@deltasigma](https://boards.straightdope.com/u/deltasigma)\ **Post date:** [February 5, 2013, 3:22pm UTC](https://boards.straightdope.com/t/the-antibiotic-apocalypse-how-scared-should-we-be/649164/45 "2013-02-05T15:22:25Z")
There are 2 mechanisms right? A cytotoxic one and a targeting one. They are independent. My focus was on the former. What is so hard about that? Now if you want to know how we make the targeting mechanism better, IDK, I’m not a molecular biologist, but I won’t accept your baseless claim that we can’t. I think there are probably any number of well conserved parts of an organism’s genome that could be used. ---
**Author:** ![DSeid](https://sea3.discourse-cdn.com/straightdope/user_avatar/boards.straightdope.com/dseid/32/20194_2.png) [@DSeid](https://boards.straightdope.com/u/DSeid)\ **Post date:** [February 5, 2013, 6:37pm UTC](https://boards.straightdope.com/t/the-antibiotic-apocalypse-how-scared-should-we-be/649164/46 "2013-02-05T18:37:50Z")
I have no knowledge as to whether or not the cytotoxic part can have resitance develop to it or not. The comment made was in response to your claim that resistance to these sorts of peptides could not develop. That is clearly a baseless claim. To use your hammer to the head analogy – you seem to be taking the perspective that learning to hide from someone with a hammer, or wearing a helmet, or having something that destroys the hammer before it reaches your head, or something that makes the aim go off, would all not count as developing defense against hammer to the head. So sure, the hammer to the head will always work if the head can be found, if no helmet is worn, and if the hammer can reach the head without being destoyed. So? What is the point of that comment? There must be more to what you are trying to say than that, because that point is amazingly trite. ---
**Author:** ![eltro102](https://avatars.discourse-cdn.com/v4/letter/e/7cd45c/32.png) [@eltro102](https://boards.straightdope.com/u/eltro102)\ **Post date:** [February 5, 2013, 6:43pm UTC](https://boards.straightdope.com/t/the-antibiotic-apocalypse-how-scared-should-we-be/649164/47 "2013-02-05T18:43:19Z")
We still have a huge array of tools being developed (or which already exist!) that can kill bacteria, such as bacteriophages (set to become more common as we can do more and more cool stuff with genetics), new non-biological methods such as nanotech coatings which can kill MRSA on contact to new enzymes with a 100% death rate so no resistance can even develop ---
**Author:** ![mozchron](https://avatars.discourse-cdn.com/v4/letter/m/c2a13f/32.png) [@mozchron](https://boards.straightdope.com/u/mozchron)\ **Post date:** [February 5, 2013, 6:57pm UTC](https://boards.straightdope.com/t/the-antibiotic-apocalypse-how-scared-should-we-be/649164/48 "2013-02-05T18:57:41Z")
Of course bacteria could evolve resistance to physical disruption. [Spore-forming bacteria anyone?](http://en.wikipedia.org/wiki/Endospore) This is often a variable trait used in response to stressful conditions. I can easily envision the evolution of tougher/thicker spore walls and a greater propensity to form spores. ---
**Author:** ![bump](https://avatars.discourse-cdn.com/v4/letter/b/7c8e57/32.png) [@bump](https://boards.straightdope.com/u/bump)\ **Post date:** [February 5, 2013, 7:40pm UTC](https://boards.straightdope.com/t/the-antibiotic-apocalypse-how-scared-should-we-be/649164/49 "2013-02-05T19:40:03Z")
> [@DSeid](#): > > So? What is the point of that comment? There must be more to what you are trying to say than that, because that point is amazingly trite. I think I understand what he’s getting at, and it may be a little more subtle than what you’re saying. What you’re saying is that bacteria can develop resistance to anything, and what he’s saying is that they can’t develop resistance to certain types of attacks/injury, specifically cell wall lysis and penetration. To use a human metaphor, we may evolve resistance to certain diseases and environmental factors, but it’s unlikely that we’ll develop resistance to being shot, drowned, or run over by a steamroller, no matter how much we mutate. That’s, I think what **deltasigma’s** trying to get at- antibiotic resistance is more analogous to some populations being resistant to plague and HIV, but these peptides are more similar to a gunshot or drowning. ---
**Author:** ![deltasigma](https://avatars.discourse-cdn.com/v4/letter/d/e5b9ba/32.png) [@deltasigma](https://boards.straightdope.com/u/deltasigma)\ **Post date:** [February 5, 2013, 9:44pm UTC](https://boards.straightdope.com/t/the-antibiotic-apocalypse-how-scared-should-we-be/649164/50 "2013-02-05T21:44:50Z")
> [@DSeid](#): > > I have no knowledge as to whether or not the cytotoxic part can have resitance develop to it or not. IOW, there’s really no point in trying to discuss this with you then. ---
**Author:** ![dstarfire](https://sea3.discourse-cdn.com/straightdope/user_avatar/boards.straightdope.com/dstarfire/32/5762_2.png) [@dstarfire](https://boards.straightdope.com/u/dstarfire)\ **Post date:** [February 5, 2013, 10:07pm UTC](https://boards.straightdope.com/t/the-antibiotic-apocalypse-how-scared-should-we-be/649164/51 "2013-02-05T22:07:41Z")
> [@FoieGrasIsEvil](#): > > Other than a perhaps misplaced faith in medicine and technology? No. As \*\*ForYou \*\*alludes to, we have become an overly sanitary society in some respects and I think I have read some reports from the medical world that indicate that we might be better off if our children played in the dirt a little more. > > I don’t know the answer. I’ve seen a few reports (likely stemming from the same study) like that, hypothesizing a link between improved hygiene and the increase in allergies and other immune system malfunctions in modern society. ---
**Author:** ![DSeid](https://sea3.discourse-cdn.com/straightdope/user_avatar/boards.straightdope.com/dseid/32/20194_2.png) [@DSeid](https://boards.straightdope.com/u/DSeid)\ **Post date:** [February 6, 2013, 1:36am UTC](https://boards.straightdope.com/t/the-antibiotic-apocalypse-how-scared-should-we-be/649164/52 "2013-02-06T01:36:15Z")
> [@bump](#): > > I think I understand what he’s getting at, and it may be a little more subtle than what you’re saying. > > What you’re saying is that bacteria can develop resistance to anything, and what he’s saying is that they can’t develop resistance to certain types of attacks/injury, specifically cell wall lysis and penetration. > > To use a human metaphor, we may evolve resistance to certain diseases and environmental factors, but it’s unlikely that we’ll develop resistance to being shot, drowned, or run over by a steamroller, no matter how much we mutate. > > That’s, I think what **deltasigma’s** trying to get at- antibiotic resistance is more analogous to some populations being resistant to plague and HIV, but these peptides are more similar to a gunshot or drowning. I’m sorry but I do not see what is additionally more subtle about that; it’s trite. What does it matter that bacteria have still not learned to deal with Amoxicillin disruption of cell wall synthesis? They are still resistant to the drug through another mechanism. The point of interest with the frog origin peptides was not that it could punch into the cell walls. That’s nothing too impressive. A whole host of antiseptics destroy cell walls. Heat does that. Problem is that those kill the host cells too. The point of interest was how these targeted bacteria and not animal cells, by being attracted to the charge of the bacterial cell wall. And it turns out that many pathogenic bacteria already have evolved ways around that. They are already prepared for this step in the arms race. Don’t get me wrong. The general subject of utilizing innate mechanisms (such as those frog peptides) to bootstrap the efficacy of antibiotics and/or or the adaptive immune system is exciting and promising. Beyond those frog peptides are a group of peptides present in human tissues called [defensins](http://microbiology.ucsf.edu/micro/pathogenesis/docs/4-8Discussion1.pdf) that work via similar mechanisms. Trying to claim, Borg-like, that resistance is futile, that _this_ is _the_ magick fix, OTOH, is just plain silly. > [@dstarfire](#): > > I’ve seen a few reports (likely stemming from the same study) like that, hypothesizing a link between improved hygiene and the increase in allergies and other immune system malfunctions in modern society. What you are referencing has often been called “the hygiene hypothesis.” Of late it has been a bit modified to [“The Old Friends Hypothesis.”](http://www.news-medical.net/news/20121003/e28098Hygiene-hypothesise28099-updated-to-e28098Old-Friendse28099-hypothesis.aspx) I love this line from that short article: > [@](#): > > “One important thing we can do”, says Professor Bloomfield, “is to stop talking about ‘being too clean’ and get people thinking about how we can safely reconnect with the right kind of dirt”. ---
**Author:** ![deltasigma](https://avatars.discourse-cdn.com/v4/letter/d/e5b9ba/32.png) [@deltasigma](https://boards.straightdope.com/u/deltasigma)\ **Post date:** [February 6, 2013, 1:41am UTC](https://boards.straightdope.com/t/the-antibiotic-apocalypse-how-scared-should-we-be/649164/53 "2013-02-06T01:41:22Z")
bump: Thank you for the attempted assist, but it’s clear that dseid and I will only continue to talk past one another. ---
**Author:** ![Leo\_Bloom](https://sea3.discourse-cdn.com/straightdope/user_avatar/boards.straightdope.com/leo_bloom/32/10377_2.png) [@Leo\_Bloom](https://boards.straightdope.com/u/Leo_Bloom)\ **Post date:** [February 6, 2013, 7:26am UTC](https://boards.straightdope.com/t/the-antibiotic-apocalypse-how-scared-should-we-be/649164/54 "2013-02-06T07:26:29Z")
I learned about spore-forming from this thread. Could we have lost an immunity that the Pharoahs had or the amber ants had (egs from cite) that could be traced to mammals? Ie, kicking off a Jurassic Park apocalypse? ---
**Author:** ![Busy\_Scissors](https://avatars.discourse-cdn.com/v4/letter/b/d78d45/32.png) [@Busy\_Scissors](https://boards.straightdope.com/u/Busy_Scissors)\ **Post date:** [February 6, 2013, 11:28pm UTC](https://boards.straightdope.com/t/the-antibiotic-apocalypse-how-scared-should-we-be/649164/55 "2013-02-06T23:28:52Z")
> [@DSeid](#): > > I’m sorry but I do not see what is additionally more subtle about that; it’s trite. > > What does it matter that bacteria have still not learned to deal with Amoxicillin disruption of cell wall synthesis? They are still resistant to the drug through another mechanism. > > The point of interest with the frog origin peptides was not that it could punch into the cell walls. That’s nothing too impressive. A whole host of antiseptics destroy cell walls. Heat does that. Problem is that those kill the host cells too. The point of interest was how these targeted bacteria and not animal cells, by being attracted to the charge of the bacterial cell wall. And it turns out that many pathogenic bacteria already have evolved ways around that. They are already prepared for this step in the arms race. > > Don’t get me wrong. The general subject of utilizing innate mechanisms (such as those frog peptides) to bootstrap the efficacy of antibiotics and/or or the adaptive immune system is exciting and promising. Beyond those frog peptides are a group of peptides present in human tissues called [defensins](http://microbiology.ucsf.edu/micro/pathogenesis/docs/4-8Discussion1.pdf) that work via similar mechanisms. Trying to claim, Borg-like, that resistance is futile, that _this_ is _the_ magick fix, OTOH, is just plain silly. > : Antimicrobial peptides are quite difficult molecules for bacteria to adapt to due to their non-selectivity - they’re not targeting an enzyme active site, say, where a point mutation is enough to bollox binding and render the antibiotic useless. The corollary to this, though, is that they don’t tend to be that effective. They’re generally not offering a killer inhibitory binding event, it’s more a low affinity propensity to disrupt bacterial cell walls through pore formation etc. So the Lord giveth and the Lord taketh away. There’s also the domesday question that if bacteria can in fact evolve resistance to these peptides, e.g. through mass modulation of surface charge or some such mechanism through massive, forced exposure to a human AMP, than our endogenous immune systems could be fucked as all creatures use these molecules as part of their innate defences. May be a bit far-fetched - I am sure there is massive variation in antimicrobial peptide structure. I believe the discussion with the clinical development of these molecules is around these issues - whether it’s worth developing them as low potency antibiotics but ones that have good prospects to resist resistance. Given the often intractable pharmacokinetic properties of peptides, it might prove too much of a ballache. Some are on the market, though - Daptomycinis one that was developed recently - think it’s structure dictates an intravenous injection. ---
**Author:** ![DSeid](https://sea3.discourse-cdn.com/straightdope/user_avatar/boards.straightdope.com/dseid/32/20194_2.png) [@DSeid](https://boards.straightdope.com/u/DSeid)\ **Post date:** [February 7, 2013, 12:14am UTC](https://boards.straightdope.com/t/the-antibiotic-apocalypse-how-scared-should-we-be/649164/56 "2013-02-07T00:14:13Z")
The linked defensins article is a good read **Busy**. The most interesting research may be in the emerging understanding of how these molecules work other than increasing membrane permeability, as immune modulators of sorts. But agreed, less likely magic bullets and more likely adjuncts to other more specific mechanisms. ---
**Author:** ![Leo\_Bloom](https://sea3.discourse-cdn.com/straightdope/user_avatar/boards.straightdope.com/leo_bloom/32/10377_2.png) [@Leo\_Bloom](https://boards.straightdope.com/u/Leo_Bloom)\ **Post date:** [February 7, 2013, 1:05am UTC](https://boards.straightdope.com/t/the-antibiotic-apocalypse-how-scared-should-we-be/649164/57 "2013-02-07T01:05:49Z")
I’m surprised no one has said this yet, but I, for one, welcome our biota overlords. ---
**Author:** ![deltasigma](https://avatars.discourse-cdn.com/v4/letter/d/e5b9ba/32.png) [@deltasigma](https://boards.straightdope.com/u/deltasigma)\ **Post date:** [February 7, 2013, 2:25am UTC](https://boards.straightdope.com/t/the-antibiotic-apocalypse-how-scared-should-we-be/649164/58 "2013-02-07T02:25:51Z")
> [@Busy\_Scissors](#): > > Antimicrobial peptides are quite difficult molecules for bacteria to adapt to due to their non-selectivity - they’re not targeting an enzyme active site, say, where a point mutation is enough to bollox binding and render the antibiotic useless. The corollary to this, though, is that they don’t tend to be that effective. They’re generally not offering a killer inhibitory binding event, it’s more a low affinity propensity to disrupt bacterial cell walls through pore formation etc. > So the Lord giveth and the Lord taketh away. > There’s also the domesday question that if bacteria can in fact evolve resistance to these peptides, e.g. through mass modulation of surface charge or some such mechanism through massive, forced exposure to a human AMP, than our endogenous immune systems could be fucked as all creatures use these molecules as part of their innate defences. May be a bit far-fetched - I am sure there is massive variation in antimicrobial peptide structure. > > I believe the discussion with the clinical development of these molecules is around these issues - whether it’s worth developing them as low potency antibiotics but ones that have good prospects to resist resistance. Given the often intractable pharmacokinetic properties of peptides, it might prove too much of a ballache. Some are on the market, though - [Daptomycin](http://Daptomycin)is one that was developed recently - think it’s structure dictates an intravenous injection. I think the link is incomplete - hoping you could fix that. 🙂 I was wondering about the peptide thing too since they’d never survive the GI tract as is. Plus I guess there would be the absorption issue. In terms of targeting, I was thinking that you would have a specific organism in mind and you would look for well conserved parts of it’s genome to target - say some membrane structure that would be visible to a free floating molecule but which couldn’t be mutated significantly w/o impairing the organism’s fitness. Only I have no idea how complex bacterial membranes are and if any such targets would be available. Thanks. 🙂 ---
**Author:** ![DSeid](https://sea3.discourse-cdn.com/straightdope/user_avatar/boards.straightdope.com/dseid/32/20194_2.png) [@DSeid](https://boards.straightdope.com/u/DSeid)\ **Post date:** [February 7, 2013, 3:24am UTC](https://boards.straightdope.com/t/the-antibiotic-apocalypse-how-scared-should-we-be/649164/59 "2013-02-07T03:24:10Z")
Not sure if this is the one Busy had but [the Wiki article](http://en.wikipedia.org/wiki/Daptomycin) is actually well written. The targets are available; targeting particular features of specific bacteria’s cell walls and membrane structures is basically the adaptive immune system. Doing it other than using antibodies is a bit more difficult. Technology for getting peptides and proteins in without IV or injection (IM or SubQ) delivery OTOH is already in progress. One promising approach is using [microneedle enabled transdermal delivery systems](http://www.ncbi.nlm.nih.gov/pubmed/22342643). ---
**Author:** ![DSeid](https://sea3.discourse-cdn.com/straightdope/user_avatar/boards.straightdope.com/dseid/32/20194_2.png) [@DSeid](https://boards.straightdope.com/u/DSeid)\ **Post date:** [February 9, 2013, 2:15am UTC](https://boards.straightdope.com/t/the-antibiotic-apocalypse-how-scared-should-we-be/649164/60 "2013-02-09T02:15:42Z")
[This article](http://intimm.oxfordjournals.org/content/17/1/1.long) may be of interest to a few here. Turns out my above post is not completely accurate. There are other conserved features that are targets of elements of the innate system using “Toll-like receptors.” The features include various lipoproteins/lipopeptides, double-stranded RNA, flagellin (part of bacterial flagella), and some particular RNA strands. Substances that promote the expression of these peptides, [antimicrobial peptide elicitors](http://www.ncbi.nlm.nih.gov/pubmed/23160387), are apparently one promising avenue. [Previous page](https://boards.straightdope.com/t/the-antibiotic-apocalypse-how-scared-should-we-be/649164.md?page=2) [Next page](https://boards.straightdope.com/t/the-antibiotic-apocalypse-how-scared-should-we-be/649164.md?page=4)