[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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