[HN Gopher] Polymers capable of killing bacteria without inducin...
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       Polymers capable of killing bacteria without inducing antibiotic
       resistance
        
       Author : geox
       Score  : 121 points
       Date   : 2023-12-22 18:07 UTC (4 hours ago)
        
 (HTM) web link (today.tamu.edu)
 (TXT) w3m dump (today.tamu.edu)
        
       | jjkeddo199 wrote:
       | I have been colonized with "mostly" dormant MRSA for a couple
       | years now. The idea of ever needing surgery terrifies me because
       | I know I could die from a flareup in the "weakened" part of my
       | body.
       | 
       | I tried fighting it in the past but the stomach damage from long
       | treatment regiments just wasn't worth it, not to mention the risk
       | of getting reinfected from my home. I hope a non-harmful and
       | reliable cure is available someday.
        
         | orangepurple wrote:
         | Where is the colonization?
        
           | kulahan wrote:
           | His body.
        
             | samstave wrote:
             | Which sector?
             | 
             | Build more Polymers.
        
         | epgui wrote:
         | MRSA is everywhere now, so being colonized by it is pretty much
         | the norm. Most _S. aureus_ is MRSA in many parts of the world.
        
         | echelon wrote:
         | How did you find out you'd been colonized?
         | 
         | Is there no way to purge it? (Isopropyl bath?)
        
           | gorkish wrote:
           | Turns out the colonists don't get along with the natives, and
           | yes, soaking your organs in antiseptic would indeed take care
           | of it!
        
             | jjkeddo199 wrote:
             | Yep. Its inside me :)
        
         | qvrjuec wrote:
         | Interesting - how is it not outcompeted by regular staph?
         | Wouldn't it be over a long enough time period without
         | introducing it to methicillin?
        
           | jjkeddo199 wrote:
           | I didn't pick up regular staph -- I picked up an already
           | moderately resistant strain that became more resistant due to
           | treatments stopped too-early due to both allergic reactions
           | (my issue), illness/vomiting due to collapsed "stomach biome"
           | (my issue), and undersized prescription lengths (doctors
           | issue).
        
         | smegsicle wrote:
         | tried fasting?
        
           | jjkeddo199 wrote:
           | Unfortunately, as a practicing Muslim, I can report that
           | doesn't help much. On the plus side, my infection doesn't
           | flare up too often -- And when it does, I have some
           | mitigations I usually take to get it to taper off.
        
         | JoshTko wrote:
         | Are there no phage treatments for MRSA yet?
        
           | jjkeddo199 wrote:
           | I could probably get decolonized by simultaneously
           | hospitalizing myself, my family, and bleaching everything we
           | own while we get pumped with heavy anti-biotic cocktails --
           | But that just isn't worth it to me.
        
       | xxpor wrote:
       | Unless it's 100% effective, how could it not induce antibiotic
       | resistance? And anything that's 100% effective is likely going to
       | do damage to something else, no?
        
         | epgui wrote:
         | You ask the right questions, and what you're suggesting is
         | correct.
        
         | echelon wrote:
         | I'd like to see them evolve isopropyl alcohol resistance. Or
         | bleach resistance. Things that the prokaryotic biology is
         | outright incompatible with.
         | 
         | Obviously not the best for human application, but it'll work in
         | the lab.
        
           | jtriangle wrote:
           | Fire cleanses all.
        
             | bigbillheck wrote:
             | For now.
             | (https://en.wikipedia.org/wiki/Deinococcus_radiodurans
             | https://en.wikipedia.org/wiki/Thermophile)
        
           | p1mrx wrote:
           | Bleach-resistant C. diff was in the news recently:
           | 
           | https://www.microbiologyresearch.org/content/journal/micro/1.
           | ..
        
           | jMyles wrote:
           | Both of these have now been observed. Of course your
           | underlying observation holds: prokaryotes nuclei are
           | fundamentally fragile in the face of these compounds.
           | However, my understanding is that in both cases, it appears
           | that microscopic pathogens are capable of rapidly evolving
           | rudimentary mechanical barriers.
           | 
           | Alcohol resistance:
           | https://www.medicalnewstoday.com/articles/322646
           | 
           | Bleach resistance:
           | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464077/
        
             | echelon wrote:
             | > it appears that microscopic pathogens are capable of
             | rapidly evolving rudimentary mechanical barriers.
             | 
             | Probably/hopefully at great cost to the organism that would
             | ordinarily allow it to be out-competed.
             | 
             | This does pose a problem, however. Especially in
             | environments where frequent sterilization takes place.
        
         | burlesona wrote:
         | From the article: "The new polymers we synthesized could help
         | fight antibiotic resistance in the future by providing
         | antibacterial molecules that operate through a mechanism
         | against which bacteria do not seem to develop resistance."
         | 
         | The word "seem" is doing a lot of work there. I guess we'll
         | have to wait and see what the long term / extensive tests show.
        
         | efitz wrote:
         | Antibiotics produce chemical effects in the bacteria; eg
         | disrupting metabolic processes. We like antibiotics because
         | they target bacteria without injuring the host. Antibiotics are
         | subject to antibiotic resistance because some bacteria are
         | resistant to the chemical mechanism used.
         | 
         | There are antibacterial substances that don't target metabolic
         | processes. They function in various ways- soap binds to the
         | bacteria and to water and allows them to be washed away. Lysol
         | uses a heavily basic solution to chemically damage the
         | bacteria. These are not 100% effective because nobody uses them
         | long enough or in enough concentration to be 100% effective,
         | because they also affect the host. I guess it's conceivable
         | that a bacterium could evolve a non-lipid cell membrane or
         | resistance to high pH, but these would be much more massive
         | mutations than slight changes in metabolism.
        
         | DistractionRect wrote:
         | It's a mechanical method of action rather that chemical (think
         | targeted receptors/activation sites). An oversimplication would
         | be to liken it to barbed wire.
         | 
         | As for you next question, they call out the need to investigate
         | making it selective for bacteria vs human cells. So it seems it
         | has no selectivity at present and will kill other things. And,
         | as I understand it, changing it from being 100% effective to
         | being selective will introduce evolutionary pressure for
         | resistence bateria strains.
         | 
         | So this might be neat for materials and creating a sterile
         | environment rather than _chasing in vivo applications.
         | 
         | Edit: autocorrect wronged a word_
        
           | bigmattystyles wrote:
           | So at this point it might as well be bleach then?
        
             | DistractionRect wrote:
             | Bleaching something is an active measure. How well you
             | clean depends on how long you let the bleach work, how
             | thorough you are at getting full/consistent coverage, how
             | frequently you sterilize the surface, etc.
             | 
             | This can be a passive way to achieve sterilization, much
             | like silver nano particles and brass surfaces have been
             | shown to passively kill bacteria, except without metal
             | working/precious metals/oxide layers that make those
             | solutions less scalable.
        
       | gentleman11 wrote:
       | > without inducing antibiotic resistance
       | 
       | Isn't that a way of saying "no bacteria can ever adapt to this
       | method of killing them"? Won't at least 0.1% of them find a way
       | to survive, and gradually adapt to this as well?
        
         | kulahan wrote:
         | >Cationic polymers are a promising class of bioactive agents,
         | which trigger bacterial cell death through physical disruption
         | of their membranes.
         | 
         | It sounds like it would be equivalent to humans evolving
         | bulletproof skin. (quote is from their original paper which is
         | linked in the article)
        
           | teppic wrote:
           | > It sounds like it would be equivalent to humans evolving
           | bulletproof skin.
           | 
           | You don't need bulletproof skin if you can avoid being shot.
        
           | roughly wrote:
           | Yeah, and I think that's where the tension is:
           | 
           | - bacteria evolve much, much faster and over a wider range of
           | capabilities than you'd think, so this is possible - hell,
           | even probable - given the range of extremophiles we've seen
           | 
           | - for practical purposes, though, every adaptation comes with
           | a cost, though, and the bacteria are not currently immune to
           | this treatment because whatever they use for their membranes
           | in absence of this threat is cheaper than something not
           | vulnerable to this, which means this adaptation is
           | disadvantaged where the polymers are not present
           | 
           | - the amount of time a bacterial colony has to evolve a
           | response is basically limited to the amount of time it takes
           | for a dose to kill the entire colony, which may not be long
           | enough to reach a solution given the distance the genome
           | would have to travel
           | 
           | - but, re: point 1, it's not guaranteed forever, which is why
           | no scientist will say so
           | 
           | - but the media sure will, and for practical purposes may not
           | be wrong
        
             | kulahan wrote:
             | The scientist in the article is quoted as saying that
             | bacteria do not appear to develop resistance to this.
        
         | xaellison wrote:
         | "bacteria do not seem to develop resistance" - Dr. Quentin
         | Michaudel
         | 
         | The press release is (predictably) more cavalier in its claim!
         | 
         | All this release says is that the polymers "[disrupt] the
         | membrane of these microorganisms". At that level of detail,
         | penicillin works similarly, and is vulnerable to resistance.
         | 
         | I'd love to know more detail about how this is a different kind
         | of disruption.
        
         | lainga wrote:
         | I thought there was a sort of "iron triangle" between
         | antibiotics and phage therapy where bacteria couldn't maintain
         | resistance to both. But OTOH phage therapy is several decades
         | old and still rarely used
        
           | corethree wrote:
           | It's well developed and used by doctors in Russia I hear.
        
         | bawolff wrote:
         | I dont see why that would be true. The liklihood of adaption
         | depends on the details of the method. Not everything is easily
         | adapted out of.
         | 
         | Humans have been shooting each other with guns, and before that
         | bows and arrows for a long time, and yet evolution hasn't
         | provided us with fire-arm resitance yet.
        
           | acover wrote:
           | Another example: boiling kills most bacteria, very few have
           | evolved to survive it.
        
           | arrowleaf wrote:
           | I'm assuming the intended application of this is to kill
           | bacteria colonizing a biological host. In order for that to
           | work, the treatment needs to be selective in what it kills.
           | If human/animal/plant cells have any mechanism to avoid being
           | killed by the antibiotic, eventually the bacteria will adapt
           | them.
        
           | BobaFloutist wrote:
           | Humans take a much much longer time to evolve than bacteria
           | (and much longer than we've been shooting each other), and
           | your average human doesn't die to gunfire before they get to
           | reproduce.
           | 
           | I'm sure if you put humans in an environment with a major
           | chance of dying to gunfire before they reproduced for
           | hundreds of millions of years or whatever we'd start to
           | develop thicker bones or something - or just earlier and
           | faster reproduction.
        
       | efitz wrote:
       | In 30 years we will be seeing class action lawsuits and
       | regulatory action about bacteria-inhibiting polymers
       | contaminating food supply and particles in the oceans.
       | 
       | No one will look back and estimate the number of lives saved;
       | they and their lawyers will simply bankrupt the company that
       | productizes this technology.
        
         | hinkley wrote:
         | Imagine these lodged in your intestines.
        
           | firtoz wrote:
           | It's ok we will produce polymer killing polymers
        
             | hinkley wrote:
             | And when winter comes it will freeze to death?
        
           | jjtheblunt wrote:
           | It's interesting you say that, as i remember seeing an
           | article years ago about asbestos in water pipes in
           | California, and thought the same as you (i think) imply:
           | that's got to be super dangerous.
        
             | jjtheblunt wrote:
             | multiple downvotes but no comments: loss of chance to share
             | presumed wisdom is a bummer for the HN community.
        
           | ssnistfajen wrote:
           | Bye-bye gut flora!
        
       | jcoc611 wrote:
       | How long until this is weaponized?
        
       | apienx wrote:
       | This is really cool and humans are amazing. You have to be
       | relentlessly resourceful to engineer a material and study it like
       | they've done.
       | 
       | If you read the paper, however, you see that it's more about
       | chemists showing off a tour de force. The application itself is
       | not exactly novel. It's a solution looking for a problem.
       | https://www.pnas.org/doi/10.1073/pnas.2311396120
       | 
       | Which takes nothing away from their remarkable effort. Kudos!
        
       | onetimeuse92304 wrote:
       | The problem with killing bacteria isn't that we are lacking ways
       | to do so. Steeping them in a strong acid should make sure they
       | are killed and they should not find a way to develop resistance
       | to a strong acid.
       | 
       | The problem is we want to kill them, while in human body, without
       | causing too much detriment to the host.
       | 
       | To do this, we essentially need to develop something that will
       | cause serious harm to the bacteria and yet not harm human cells.
       | This means exploiting various differences between bacteria and
       | humans.
       | 
       | A polymer that kills cell walls indiscriminately is hardly an
       | acceptable solution for a human. Yes, bacteria may not be able to
       | gain resistance to it but also it can't ever be used on a real
       | human because mass cell death will cause too much damage to the
       | human.
       | 
       | And "solving the problem of selectivity" will cause bacteria to
       | be able to find their resistance eventually. Because if it is
       | possible to escape your cell wall getting disrupted because you
       | have specific DNA -- a bacteria can gain resistance.
       | 
       | I am firmly of the opinion it is not possible to develop an
       | antibiotic guaranteeing the bacteria will not be able to gain
       | resistance to it.
       | 
       | Simply -- the resistance can be had as evidenced by human cells.
       | And the genetic material is abundantly available to the bacteria
       | -- they are pretty much surrounded by it while in our bodies.
       | There is always going to be non-zero chance for resistance to be
       | acquired by a cell and then spread to the offspring.
        
         | londons_explore wrote:
         | > I am firmly of the opinion it is not possible to develop an
         | antibiotic guaranteeing the bacteria will not be able to gain
         | resistance to it.
         | 
         | I think the main approach to prevent antibiotic resistance is
         | coming up with a way to prevent bacteria ever coming across a
         | low dose of the antibiotic. As long as we make sure the dose is
         | either huge or zero, antibiotic resistance shouldn't evolve.
         | 
         | Unfortunately, humans aren't a well controlled lab experiment -
         | and there will always be people taking a half-dose, or flushing
         | the antibiotics down the drain where they get diluted and
         | suddenly trillions of sewer bacteria get exposed to a low dose
         | and suddenly start developing resistance.
        
           | onetimeuse92304 wrote:
           | > I think the main approach to prevent antibiotic resistance
           | is coming up with a way to prevent bacteria ever coming
           | across a low dose of the antibiotic (...)
           | 
           | That's not the only way. We have more ways:
           | 
           | * use low dose of antibiotic to kill enough bacteria to let
           | the immune system to deal with the rest. Then ensure the
           | subject is cured until all bacteria are killed so that none
           | escape. Low dose might be needed because most antibiotics are
           | actually pretty harmful and the harm is managed with low
           | dose.
           | 
           | * use more than one antibiotic in combination with the idea
           | there is very little chance bacteria will gain resistance to
           | both of them at the same time.
           | 
           | * use the antibiotic only as a last resort. This is
           | especially useful for bacterias that are not very harmful
           | normally, but might become harmful for certain subjects (for
           | example, immunosuppressed). If a bacteria with resistance
           | escapes, the resistance might not be very useful advantage in
           | outside environment where people do not need any help to
           | fight off infection or when infection can be more routinely
           | treated with another antibiotic.
           | 
           | Again, these are our current strategie
        
           | mike_hock wrote:
           | We don't need to develop an antibiotic that's impossible to
           | gain resistance to. We just need to stay ahead of the
           | cat&mouse game, which can go around in circles. If we start
           | using a completely new type of antibiotics and stop using the
           | old ones for a century, bacteria will gradually lose
           | resistance to the old ones as they gain resistance to the new
           | ones.
        
           | Dalewyn wrote:
           | >suddenly trillions of sewer bacteria get exposed to a low
           | dose and suddenly start developing resistance.
           | 
           | I think you're misunderstanding how resistances work.
           | 
           | Bacteria don't "start developing" resistance, if they survive
           | the antibiotic at all _they already had resistance_ by stroke
           | of luck. The surviving, resistant bacteria will subsequently
           | survive and outnumber the dead, not-resistant bacteria and we
           | generally call this  "developing resistance", but the
           | resistance itself is down to a simple question of whether it
           | was already there or not.
           | 
           | Resistances do not come to existence after bacteria come
           | across an antibiotic. If resistance is there, the dosage
           | won't matter because the resistant bacteria will survive
           | regardless.
        
             | e_y_ wrote:
             | I think the OP's statement is perfectly fine.
             | 
             | We don't really care which of those trillions of sewer
             | bacteria carries the pre-existing genes that resist an
             | anti-biotic; we care when a new strain starts becoming
             | prevalent and decreasing the effectiveness. From our
             | perspective, it's a new resistant strain.
        
         | lemmsjid wrote:
         | I am as layperson as they get on this subject matter, but I
         | would think that even if your statement is true, perhaps we can
         | get to the point where bacteria need to evolve so much to
         | overcome new antibiotic approaches that they lose some of the
         | properties that make them harmful and transmissible, i.e. it
         | becomes harder for them to exist outside of the host, penetrate
         | the host's defenses, etc. At some point a bacteria would need
         | to seem so like a human cell or beneficial bacteria that it
         | becomes non-harmful.
        
           | erikerikson wrote:
           | https://xkcd.com/810/
        
           | dkz999 wrote:
           | >... the point where bacteria need to evolve so much to
           | overcome new antibiotic approaches that they...
           | 
           | Can't. Changed it a bit for ya.
           | 
           | This is the zone we need to be in for any successful
           | treatment. This is also why e.g. humans will never evolve
           | bullet resistance.
        
         | vmarovic wrote:
         | > A polymer that kills cell walls indiscriminately is hardly an
         | acceptable solution for a human.
         | 
         | Human cells don't have cell walls, so it would not affect them.
        
           | onetimeuse92304 wrote:
           | Funny... you are actually right.
           | 
           | But there are also bacteria without cell walls.
        
         | BiteCode_dev wrote:
         | The thing is, we need to kill bacterias in many other places
         | than the human body:
         | 
         | - medical equipment: handles for scalpels, syringes, operation
         | tables... All those things we need to clean again and again.
         | 
         | - passage ways: doors, handles, stairs handrails, subway grab
         | bars... All the things that propagate infections in very dense
         | populated areas.
         | 
         | - research fabs: hazmat suits, protection googles, fum hood
         | protections,... All the stuff you want to make sure don't end
         | up cross contaminate your batch or escape.
         | 
         | So it's still very useful.
        
           | heavyset_go wrote:
           | > _- medical equipment: handles for scalpels, syringes,_
           | 
           | I hope these things are autoclaved and not just disinfected.
        
             | Cerium wrote:
             | They also need to be mechanically cleaned. Simply sterile
             | is not sufficient due to the presence of pyrogens after
             | sterilization.
             | 
             | https://ethidelabs.com/depyrogenation-and-sterilization-
             | for-...
        
             | BiteCode_dev wrote:
             | Yes, but once they are out of their container, they start
             | collecting bacterias.
             | 
             | No matter how clean operating rooms are (which can vary a
             | lot), it's never perfectly sanitized.
             | 
             | A cheap way to get many surfaces agent free would be a nice
             | additional safety measure.
        
             | EA-3167 wrote:
             | It depends on the instrument, you can't autoclave the scope
             | used for cystology for example, they're generally treated
             | with vaporized Hydrogen peroxide. It's very effective, but
             | not as effective as an autoclave.
        
           | smileysteve wrote:
           | Out of the body, we have a number of solutions; fire, bleach,
           | uv-c, lye; on your list, only the plastics (personal
           | protection stuff) can't cleaned with these many times around
        
             | notamy wrote:
             | Unfortunately, bacteria resistant to bleach are starting to
             | develop https://www.microbiologyresearch.org/content/journa
             | l/micro/1...
        
         | sitharus wrote:
         | > To do this, we essentially need to develop something that
         | will cause serious harm to the bacteria and yet not harm human
         | cells.
         | 
         | The other problem is we depend on mutualistic bacteria to
         | survive, if we kill all bacteria in our bodies we'll die of
         | malnutrition. And even worse sometimes the problem is those
         | mutualistic bacteria getting out of balance, so we need to kill
         | some while promoting an increase of others.
         | 
         | And those bacteria are constantly topped up from the
         | environment, so we can live in a sterile environment our whole
         | lives. It's a delicate balance, we can't just throw anti-
         | bacterial things around without thought.
        
           | onetimeuse92304 wrote:
           | Usually antibiotic treatments do kill significant portion of
           | bacterial flora.
           | 
           | That's why antibiotics are typically followed by probiotic
           | preparations to replenish our bodies with "good" bacteria.
           | This is not necessarily done to prevent us from dying of
           | malnutrition. The bigger problem is that lacking "good"
           | bacteria, we can have "bad" bacteria take over the void,
           | causing even more problems.
        
       | ssnistfajen wrote:
       | How will the degradation of this material impact the environment
       | should it see mass application some day?
        
       | HankB99 wrote:
       | I wonder if this will provide any way to deal with resistant
       | tuberculosis. One of the treatments for MDR TB is removing the
       | infected portion of the lung.
       | https://pubmed.ncbi.nlm.nih.gov/26757804/
        
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