Polymers capable of killing bacteria without inducing antibiotic resistance
today.tamu.edu
today.tamu.edu
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.
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.
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
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.
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.
That’s not how evolution works. A few bacteria could be resistant to low doses. After the low dose, and a short wait, now the entire population is resistant to the low dose.
That gives them a much better starting point for mutations to the resistance gene and for crossing with bacteria that have some other complimentary resistance gene.
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.
Human cells don’t have cell walls, so it would not affect them.
But there are also bacteria without cell walls.
- 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.
I hope these things are autoclaved and not just disinfected.
https://ethidelabs.com/depyrogenation-and-sterilization-for-...
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.
Sterilizing those often increases disease spread. By default, they are covered with a microbial community that can outcompete things that are human pathogens.
If you sterilize it, then you’re either leaving a coating of food (mostly dead skin cells) for pathogens to eat, or a coating of nasty poisons that strip the protective barrier off people’s skins, which undermines their ability to fight off what pathogens they do end up touching.
Probiotics can be applied to mitigate undesirable bacterial growth after sanitizing [1].
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.
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.
On the contrary. Animal cells do not have cell walls. They have cell membranes but that's a different thing. Many existing antibiotics interfere with the cell walls of bacteria.
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!
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?
It sounds like it would be equivalent to humans evolving bulletproof skin. (quote is from their original paper which is linked in the article)
You don’t need bulletproof skin if you can avoid being shot.
- 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
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.
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.
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.
Obviously not the best for human application, but it'll work in the lab.
https://www.microbiologyresearch.org/content/journal/micro/1...
Alcohol resistance: https://www.medicalnewstoday.com/articles/322646
Bleach resistance: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464077/
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.
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.
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.
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
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.
A more apt explanation would be to liken it to diatomaceous earth vs. pesticides. Insects can develop resistance to poisons, but when they cross diatomaceous earth it pierces their waxy exoskeleton coating and causes them to lose moisture, dry out, and eventually die... and evolution hasn't found a way around that yet.
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.
Build more Polymers.
Is there no way to purge it? (Isopropyl bath?)
I take that probiotic, sold as Evivo in the US, and Layer Origin 2’FL HMO and use it with my children.
1. https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(2...
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.