Antibiotic resistance. Suggested tactics

[mistermack]

I'm going to start off with my own suggestion. But the thread would maybe more valuable if it was open to other suggestions, and the latest news.

My own idea, ( which I'm not wedded to, but I think it's worth proposing ) is to fight bugs with bugs. 

The bugs are evolving antibiotic resistance by natural selection. But selective breeding works quicker than evolution. If a nasty bug has evolved resistance, how long would it take to BREED  a strain with the opposite characteristic? i.e.   A strain of the same bug that keels over at the slightest hint of the cheapest antibiotic. What use would that be ? Well, instead of trying to scrub every nook and cranny clean, you could dust or spray with a culture of your specially bred bacteria, so that if a patient gets an infection, the chances are it will be one of your super-sensitive bugs that caused it, and not one of the resistant strain.

If that were to happen, the infection would be quickly and cheaply cleared using a stock antibiotic.

Maybe the nasty ones could be crowded out by your sensitive ones in the environment. The only place where the resistant bugs would have an advantage would be on or inside the patient who was on a course of antibiotics. Everywhere else, it would just be a numbers game which you could win by breeding your creation in it's billions. You could even get visitors to dust their hands and faces with your created bugs, so that if they picked up a resistant bug, it would find itself crowded out, before it could be passed on.

I dreamed this idea up years ago, and also foresaw drawbacks with it. I can't remember what they were but I'll post them if they come back to me. 

Any other ideas welcome.  

[hypervalent_iodine]

You realise of course that resistance can be an acquired trait as well as an inherent one? 

[mistermack]

15 minutes ago, hypervalent_iodine said:

You realise of course that resistance can be an acquired trait as well as an inherent one? 

I'm not pretending to be well-read in the subject, so no it hasn't occurred to me. But if that were a serious factor, then maybe the exchange could go the other way too. i.e. Your specially bred bugs could pass genes to the resistant ones, weakening their resistance? 

[hypervalent_iodine]

It is quite a serious factor, and one of the reasons why resistance is on the rise. One of the issues with your last statement is that you still plan to try and kill these microorganisms with antibiotics. This places selective pressure on the population such that the individuals more likely to survive and replicate are the ones that are resistant. 

[CharonY]

None of that would work based on our understanding of basic microbiology. First, genetically engineered organisms are usually not terribly competitive. Also there are many different reservoirs of resistant bacteria and it is virtually impossible to replace them with sensitive strains. Take wastewater, for example, a huge reservoir of resistant bugs. There is no physical means to replace that biota with something artificial, other than sterilizing the everything, put the new strains in. And even then, unless everything is kept perfectly sterile, as long as there is selective pressure, selective bugs will become dominant again.

In other surface it amounts to the same issue, there is generally no way to simply stabilize an artificial microbiota. And as hypervalent mentioned, the moment antibiotics in play, the selection favours the rise of antibiotic bacteria again.

[mistermack]

11 minutes ago, hypervalent_iodine said:

It is quite a serious factor, and one of the reasons why resistance is on the rise. One of the issues with your last statement is that you still plan to try and kill these microorganisms with antibiotics. This places selective pressure on the population such that the individuals more likely to survive and replicate are the ones that are resistant. 

I did say that the one place that resistant strains would have the advantage is inside the patient being treated with antibiotics. That's obvious. However, if the initial infection is by a sensitive strain, then it's easily cleared. The idea is that if you do pick up the bug, it's far more likely to be one of the sensitive strain than a resistant one, because of the numbers factor. 

A resistant bug would have no initial advantage, if the patient was not yet on a course of antibiotics. 

12 minutes ago, CharonY said:

First, genetically engineered organisms are usually not terribly competitive.

I didn't suggest genetically engineering them. I said selectively bred. And of course, like cattle, you could keep improving the breed as time goes on.

16 minutes ago, CharonY said:

Take wastewater, for example, a huge reservoir of resistant bugs. There is no physical means to replace that biota with something artificial,

Resistant bugs only evolve resistance on or inside the animal being treated with the antibiotic. And that's the only place that they have an advantage. I can't see wastewater having enough antibiotic in it to ever enable resistance to evolve. 

In a hospital, if you do your normal thorough cleaning, then the remaining numbers of the resistant strain would be very low. Then you dust or spray with your sensitive strain, the resistant strain will be a minute percentage in the environment and hopefully get crowded out before they can infect someone. It could even be possible that the sensitive strain could stimulate an immune reaction in a patient, and prevent infection from a much worse resistant one. 

Also, as I suggested, if visitors got the dust or spray treatment, then any resistant bug that they picked up and carried out would be in the minute minority, and be less likely to get passed around from person to person.

[CharonY]

39 minutes ago, mistermack said:

I didn't suggest genetically engineering them. I said selectively bred. And of course, like cattle, you could keep improving the breed as time goes on.

There is not a huge difference as far as lab strains go. Due to the fairly permissive situation in the lab the strains are not competitive. What you would need to do is recreate a bacterial community for almost any possible surface and reservoir.

Quote

However, if the initial infection is by a sensitive strain, then it's easily cleared. 

How would that happen? Unless you spread AB-sensitive pathogens around (and get arrested for bioterrorism). Sensitivity is not a particular trait that spreads around.

 

39 minutes ago, mistermack said:

Resistant bugs only evolve resistance on or inside the animal being treated with the antibiotic.

Nope, everywhere where you can find antibiotics you select for those bugs. These include wastewater, manure and basically everywhere they end up, ranging from soil to water sources. This is why the current situation has become so dire.

 

39 minutes ago, mistermack said:

get crowded out before they can infect someone.

It again implies something that is competitive. In a given environment. Unless you want to smear everything with a biofilm, which again is a horrible idea. If only because you cannot prevent the strains put out not to acquire or become resistant.

Look, you need to know the basics of resistances. Some of which require a simple point mutation. You cannot breed that away, bacteria are not cattle.  Even if we only think about more complex systems, such as efflux pumps, what is going to happen is that the existing traits will spread including through your artificial population (assuming they manage to persist a significant time frame), creating a brand new reservoir of resistances.

It is simply a bad and unrealistic idea. 

[hypervalent_iodine]

30 minutes ago, mistermack said:

I did say that the one place that resistant strains would have the advantage is inside the patient being treated with antibiotics. That's obvious. However, if the initial infection is by a sensitive strain, then it's easily cleared. The idea is that if you do pick up the bug, it's far more likely to be one of the sensitive strain than a resistant one, because of the numbers factor.

A resistant bug would have no initial advantage, if the patient was not yet on a course of antibiotics.  

 

You're missing the point. If there are resistant strains about, and you are treating infection of the sensitive strain with antibiotics, the resistant strain will quickly outcompete the sensitive strains. I also mentioned that acquired resistance exists. My work is in antifungals, but bacteria are similar in the sense that populations that are not initially resistant can become resistant over time through exposure. As CharonY said, you don't appear to know much about resistance mechanisms and how it can spread. I would suggest reading up on it and then revisiting your idea to understand why it won't work, bioterrorism aspects notwithstanding. 

 

[CharonY]

I should also clarify why I said it was bad. To be precise, it is also dangerous. While there are strains out there that are considered to be safe, we do not actually know if we put them in high concentration somewhere where they should not, e.g. due to inhalation. Opportunistic pathogenesis can arise under these conditions, which is really bad news.

[hypervalent_iodine]

8 minutes ago, CharonY said:

I should also clarify why I said it was bad. To be precise, it is also dangerous. While there are strains out there that are considered to be safe, we do not actually know if we put them in high concentration somewhere where they should not, e.g. due to inhalation. Opportunistic pathogenesis can arise under these conditions, which is really bad news.

Not to mention the risk to people already highly susceptible towards infection or for whom antibiotics / antifungals are contraindicated. 

[mistermack]

3 minutes ago, hypervalent_iodine said:

You're missing the point. If there are resistant strains about, and you are treating infection of the sensitive strain with antibiotics, the resistant strain will quickly outcompete the sensitive strains.

You're not really making a lot of sense. If a patient has an infection, it's likely to be one strain or the other. Are you suggesting a patient is likely to be infected with both strains at once? How often would that happen? If he has the sensitive strain, it can be cleared quickly and fully. If he has the resistant strain, he is no worse off than he would be now. But it's far more likely that he will get the sensitive strain, because you clean first, and then introduce the safe strain. 

22 minutes ago, hypervalent_iodine said:

are similar in the sense that populations that are not initially resistant can become resistant over time through exposure.

And as I asked before, why would that not happen in the opposite direction? 

20 minutes ago, CharonY said:

I should also clarify why I said it was bad. To be precise, it is also dangerous. While there are strains out there that are considered to be safe, we do not actually know if we put them in high concentration somewhere where they should not, e.g. due to inhalation. Opportunistic pathogenesis can arise under these conditions, which is really bad news.

You're talking as if these things can't be tested first. In an industry where everything is tested first.

41 minutes ago, CharonY said:

Nope, everywhere where you can find antibiotics you select for those bugs. These include wastewater, manure and basically everywhere they end up, ranging from soil to water sources. This is why the current situation has become so dire.

Far more likely that the selection happens INSIDE the host, and the results then get flushed into the wastewater and manure etc. Which has the highest concentration of antibiotics, the pig or the dung heap ? 

[Adamkins IV]

Your idea is to create a weak strain of a pathogen and purposely infect people with it, so that the strong version of that pathogen won't also infect the person, then we can cure that weak version?  It sounds a bit similar to a vaccination?  There is also the idea of using bacteriophages which specifically feed on bacteria which are harmful to us and infecting ourselves with those bacteriophages in order to gain immunity to that bacteria.  Why not continue to selectively breed the bacteria in your idea until they become actually beneficial for humans and don't give us any negative effects but in fact very positive effects.  Perhaps you can create a new breed of bacteria that will improve us and everyone will want to have it.  The problem with these ideas also is what if it mutates, the bacteriophage or the bacteria you've bred, it could turn into something harmful to us at some point.  All things to think about!  I like that your ideas are thinking of new things.

[hypervalent_iodine]

44 minutes ago, mistermack said:

because you clean first, and then introduce the safe strain.

Okay, several things. Cleaning doesn't remove everything. In the fungal world there are species that can colonise hospital surfaces and persist for up to 2 weeks without moisture, even after cleaning (see: Candida auris). Some strains make biofilms, which are resistant to disinfectants. Resistance to cleaning products may also be an acquired trait. Point being, you're not going to remove all of it and good luck stopping resistant strains from colonising patients just because they already have an infection from something else. Moreover, once you've cleared the infection of your susceptible strain, do you honestly think that the other pathogens hanging around won't infect? In reality, you've left them a lovely little niche ripe for abuse. And finally, resistance can be an acquired trait. This can happen during treatment. I'm going to switch back to fungi here because that's what I know, but there are cases where treatment with drugs that were initially effective stopped working before the course was finished because the fungi (Candida auris again) became resistant. 

53 minutes ago, mistermack said:

You're talking as if these things can't be tested first. In an industry where everything is tested first.

I would seriously question any ethics board that let you test this in animals / humans. 

[t686]

You can fight bacteria with moldy water.  I use it myself as a lid under an aquarium that grows moldy with water down there, and syringe it into the dirted tank.  The bacteria was making me sick until I added mold, and it has to cycle like a regular aquarium, adding it daily until it grows on the gravel and dirt  and then you don't have to add it any more.

What also controls bacteria is minerals and you can collect that during a rain where water flows over something rocky or concrete but best if it's like a concrete culvert that's homemade going over grass like a run where the water above is flowing over grass and pinestraw at the top of the hill and then flows over your culvert.  I'm trying to see if the moldy water will clear the mineral water because it's darker like iced tea, but doesn't smell bad due to the minerals.

 

[Sensei]

Quote

Antibiotic resistance. Suggested tactics

Antibiotics fight with bacteria. Bacteria can have altered DNA by viruses. There could be prepared custom virus attacking just enemy bacteria at interest. It does not even have to kill bacteria. It could just change bacteria DNA in such a way to have slower rate of reproduction, or change them to being antibiotics helpless again, reversing acquired resistance.

 

Edited October 17, 2019 by Sensei

[Sensei]

"Feeding mice helps them to fight viral infection, whereas starvation is a better strategy against bacterial infection — lending support to the proverb 'feed a cold, starve a fever'.

Ruslan Medzhitov and his colleagues at Yale University School of Medicine in New Haven, Connecticut, studied the effects of feeding on mice that were infected with either the bacterium Listeria monocytogenes or an influenza virus. Bacterium-infected mice that were deprived of food stayed alive, whereas well-fed animals died. By contrast, almost all mice with flu died when they were starved, but most survived when they were fed. During bacterial inflammation, glucose from food inhibited a metabolic process that protects brain tissue from damage, whereas the sugar protected the brain during viral inflammation."

https://www.nature.com/articles/537283c

 

[CharonY]

On 10/16/2019 at 11:24 PM, Sensei said:

Bacteria can have altered DNA by viruses.

Bacteria also freely mutate on their own.

 

On 10/16/2019 at 11:24 PM, Sensei said:

There could be prepared custom virus attacking just enemy bacteria at interest.

That would be bacteriophages and they are already in use. Phage therapy has been used since the Soviet Union. However,  they have a lot of limitations,  including the fact that they are highly targeted and have narrow uses. But there are more issues, which is why antibiotics have become so successful when they were available. They are getting now a revival because of the rise of resistances. However you generally would not want just to try resistance, as there would be no point to it. If phages were to reverse resistance in some strains, there would still be selective pressure to acquire resistance. So in order to suppress you would need to flood the patient with more phages and more antibiotics, which is not really a good therapy.

[mistermack]

On 10/17/2019 at 3:19 AM, hypervalent_iodine said:

good luck stopping resistant strains from colonising patients just because they already have an infection from something else.

Well actually, that could happen. If the patient gets infected by the sensitive strain, it could get the immune system up and ready with antibodies in place so that the resistant strain could struggle to get a foothold. It's only a possibility, but it could happen. Even though you kill off the infection with an antibiotic, the protection could linger on for some time.

 

On 10/17/2019 at 3:19 AM, hypervalent_iodine said:

I would seriously question any ethics board that let you test this in animals / humans. 

You could say that about any new process or drug. What's different about this?

On 10/17/2019 at 3:01 AM, Adamkins IV said:

Your idea is to create a weak strain of a pathogen and purposely infect people with it, so that the strong version of that pathogen won't also infect the person, then we can cure that weak version?  It sounds a bit similar to a vaccination?

No, not purposely infect people. Just flood the environment with the weak strain, after cleaning, so that the resistant strain is crowded out. 

The idea is that the resistant strain will struggle to compete for space. Even on the person of patients and visitors, the resistant strain would not have and advantage. Only on a patient who is already on a course of antibiotics would the resistant strain have the edge. 

The point was made by Hypervalent Iodine that the sensitive strain that you've created could acquire resistant genes from the nasty version, which is true. But since regular cleaning would of course continue, those acquired genes would get flushed away, and new fully sensitive versions would be re-applied every time. So if there was any gene transfer going on, it would only act to dilute the resistance, in the hospital environment. 

[mistermack]

On 10/17/2019 at 8:02 AM, Sensei said:

"Feeding mice helps them to fight viral infection, whereas starvation is a better strategy against bacterial infection — lending support to the proverb 'feed a cold, starve a fever'.

Ruslan Medzhitov and his colleagues at Yale University School of Medicine in New Haven, Connecticut, studied the effects of feeding on mice that were infected with either the bacterium Listeria monocytogenes or an influenza virus. Bacterium-infected mice that were deprived of food stayed alive, whereas well-fed animals died. By contrast, almost all mice with flu died when they were starved, but most survived when they were fed. During bacterial inflammation, glucose from food inhibited a metabolic process that protects brain tissue from damage, whereas the sugar protected the brain during viral inflammation."

https://www.nature.com/articles/537283c

 

That's interesting, but I always thought that the main difference between a cold and flu was that with flu you run a high fever, and with a cold you don't. So if this Yale study is right, feed a cold/starve a fever would be bad advice for flu, as it's viral, but that's probably where the saying comes from. 

[MigL]

It doesn't really work that way.
Any population will have varying degrees of resistance to antibiotic agents, such that !0 % ( as an example ) would be completely impervious to that agent; even your so-called weaker breed.
Once the 90 % that are affected are killed off, the remaining 10 % will spawn a generation of bacteria that is immune o that specific agent.
Once the agent is removed however, over a period of time, random processes reintroduce weaker strains that are sensitive to that agent again.

The usual therapy, that was used before/after my eye operations, is using one gent to kill 90 % of bacteria, leaving the 'stronger' 10 %,and after two weeks switch to another agent ( yes, most poisoning has a 'half-life' ) which may kill another 90 % of the 'stronger' strain. You now have 1 % remaining, and you can repeat with a third agent, if needed, and so on.
This can be repeated until you run out of antibiotic agents, but you will never get rid of all the population.

Edited October 22, 2019 by MigL

[hypervalent_iodine]

On 10/19/2019 at 7:50 PM, mistermack said:

Well actually, that could happen. If the patient gets infected by the sensitive strain, it could get the immune system up and ready with antibodies in place so that the resistant strain could struggle to get a foothold. It's only a possibility, but it could happen. Even though you kill off the infection with an antibiotic, the protection could linger on for some time.

Citation needed. 

 

On 10/19/2019 at 7:50 PM, mistermack said:

You could say that about any new process or drug. What's different about this?

Because what you are suggesting is inherently unpredictable in its outcomes, more likely to be dangerous than helpful, and doesn't appear to have the foundation of good science to support it. 

[mistermack]

11 hours ago, hypervalent_iodine said:

Citation needed.

It's you that needs to provide a citation. I only said it's a possibility. If you disagree, explain why it's not a possibility, or perhaps you could cite your evidence. 

11 hours ago, hypervalent_iodine said:

Because what you are suggesting is inherently unpredictable in its outcomes, more likely to be dangerous than helpful, and doesn't appear to have the foundation of good science to support it. 

That's just more hand waving from you. No specific argument, just tush tush ! Or maybe you can provide citations for the above claims. 

I get the feeling that some people are thinking I'm suggesting deliberately infecting people with a sensitive strain. That's not it at all. I'm suggesting that the sensitive strain should be sprayed or dusted around the risky environment, like a hospital ward that has a particular resistant bug problem. You would breed a strain of the same species, that is hyper sensitive to the usual antibiotics. It wouldn't be hard to do. If you can breed a chihuahua from a wolf, you can use selection in bacteria with a deliberate aim in mind. They reproduce so fast, it wouldn't take forever. It wouldn't have to be an expensive process, and results should get better and better over time.

You could at the same time try to select for the most competitive ones, that tended to compete better for space.  

The treatment aim would still be to prevent any infection in all patients, but the intended outcome would be that if an infection did arise, it would be far more likely to be the easily treatable kind. 

If you could break the cycle of resistant bugs having the place to themselves, It might be possible to remove the problem from the ward or hospital in question. 

[dimreepr]

3 minutes ago, mistermack said:

It's you that needs to provide a citation. I only said it's a possibility. If you disagree, explain why it's not a possibility, or perhaps you could cite your evidence. 

Yep, that's your MO. 

6 minutes ago, mistermack said:

I'm suggesting that the sensitive strain should be sprayed or dusted around the risky environment, like a hospital ward that has a particular resistant bug problem.

What you're suggesting is the exact reason why there's antibiotic resistance. 

You can't preemptively strike an evolutionary process; it's like trying to punch smoke...

[mistermack]

11 minutes ago, dimreepr said:

You can't preemptively strike an evolutionary process; it's like trying to punch smoke...

So you haven never heard of selective breeding then? Did god make the Pekingese, or maybe natural selection produced all of the lapdogs. 

Darwin would put you right, if he was here. He was fascinated by pigeon breeding, and knew all about the power of selection, whether it be natural or human. 

In reality, bacteria wouldn't care who or what was doing the selection. Humans selecting the most sensitive, or nature selecting the most resistant, it's the same process. 

13 hours ago, MigL said:

It doesn't really work that way.
Any population will have varying degrees of resistance to antibiotic agents, such that !0 % ( as an example ) would be completely impervious to that agent; even your so-called weaker breed.

Using the same argument, you would say that 10% would be hyper-sensitive to the agent. If you select that 10% and breed from them, what do you get? 

Edited October 22, 2019 by mistermack

[dimreepr]

1 minute ago, mistermack said:

So you haven never heard of selective breeding then? Did god make the Pekingese, or maybe natural selection produced all of the lapdogs. 

Darwin would put you right, if he was here. He was fascinated by pigeon breeding, and knew all about the power of selection, whether it be natural or human. 

In reality, bacteria wouldn't care who or what was doing the selection. Humans selecting the most sensitive, or nature selecting the most resistant, it's the same process. 

LOL, that's a heapin helpin of straw, man.  

But if we run with your analogy, what you're saying is, when we selectively breed, we can create almost any shape dog we want, right?

I'll leave you to ponder...