Antibiotic resistance. Suggested tactics

[mistermack]

2 minutes ago, dimreepr said:

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...

You certainly have left me pondering !   

[dimreepr]

Just now, mistermack said:

You certainly have left me pondering !   

I'd say, "you're welcome", but I'm sure you ponderance is one of revenge, rather than learning; I hope I'm wrong.

23 minutes ago, mistermack said:

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? 

A bacteria that's easily killed... And?

[hypervalent_iodine]

2 hours 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

I’ve explained why it’s false using easily verified science. As I and others have said, you lack a basic understanding of resistance. This isn’t a slight on you, but you would do well to perhaps spend more time researching the topic and educating yourself before you start accusing people who work in the area that they don’t know what they’re talking about. 

[mistermack]

Just now, hypervalent_iodine said:

I’ve explained why it’s false using easily verified science. As I and others have said, you lack a basic understanding of resistance. This isn’t a slight on you, but you would do well to perhaps spend more time researching the topic and educating yourself before you start accusing people who work in the area that they don’t know what they’re talking about. 

What am I supposed to think? This is just more hand waving. If you can't be specific, and just keep coming out with this kind of vague rubbish, you inevitably invite that kind of suspicion. When people know what they're talking about, they generally get straight to the point.

2 hours ago, dimreepr said:

A bacteria that's easily killed... And?

And that's how selective breeding works.

[dimreepr]

8 minutes ago, mistermack said:

And that's how selective breeding works.

Next, crusifiction? Good, out of the door line on the left one cross each...

[mistermack]

1 minute ago, dimreepr said:

Next, crusifiction? Good, out of the door line on the left one cross each...

No, it's freedom for me. They said I hadn't done anything, and that I could go free. 

 

 

Only kidding !

[dimreepr]

4 minutes ago, mistermack said:

No, it's freedom for me. They said I hadn't done anything, and that I could go free. 

Not in this thread...

Edited October 22, 2019 by dimreepr

[CharonY]

52 minutes ago, mistermack said:

What am I supposed to think?

Very simple. Go and read up on mechanisms of antibiotics resistance it would also help to look at, say bacterial replication. After you read it, think a little bit what selective breeding of a weaker strain would actually mean. Specifically how can you ensure that there will be susceptible pathogens to infect people with? You also seem to have a problem in realizing the difference between pathogens (who infect folks) and the regular microbiota (who mostly don't). Obviously, if you create sensitive harmless strain, you seem to believe that it somehow can spread to pathogens. 

The issue is that you do not quite understand how little you understand about microbes and that seemingly prevents you from noticing the why, fundamentally, the idea makes no sense. It was shown that just highlighting the mechanisms that you fail to understand is insufficient to make you see the issues. The only alternative is to provide a short lecture on microbial genetics but since that would most likely fall on deaf ears, I am not sure how to proceed. There is simply no foundation to build on that I can see. Many points have already been made regarding how resistances arise and spread as well as that it is almost impossible to fully replace existing microbiota (and the fact that we all carry resistant strains with us already). Or that we have far more reservoirs than you believe and so on.

[mistermack]

2 minutes ago, CharonY said:

Specifically how can you ensure that there will be susceptible pathogens to infect people with?

You haven't got a grasp of this at all. Either you're not reading what's posted, or you can't take it in. For hopefully for last time, the aim is NOT to infect people. How many times does it need to be repeated ?

[CharonY]

On 10/16/2019 at 4:48 PM, mistermack said:

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.

Just now, mistermack said:

You haven't got a grasp of this at all. Either you're not reading what's posted, or you can't take it in. For hopefully for last time, the aim is NOT to infect people. How many times does it need to be repeated ?

 

[mistermack]

Charon, I think you are beyond help. The above does NOT imply that you are trying to infect a patient. The OP was perfectly clear. The tactic is to out-compete the resistant strains in the environment, with specially bred benign strains. 

If the patient DOES pick up an infection, then it's far more likely to be from one of the sensitive strain, which would be extremely easy to clear. But that's not the intention of the process. It's just something that could happen. 

The intention is to produce an environment that has ever lower numbers of the resistant strain, through competition for space in the environment.

Edit : Just to add to that, people are often put on antibiotic after an operation anyway, so the chances of getting infected by the sensitive strain, in those circumstances, would be close to nil.

Edited October 22, 2019 by mistermack

[CharonY]

56 minutes ago, mistermack said:

If the patient DOES pick up an infection, then it's far more likely to be from one of the sensitive strain, which would be extremely easy to clear. But that's not the intention of the process. It's just something that could happen. 

This refers back to the basic issue that you simply fail to understand basic microbiology. An infection is caused by a pathogen, a specific bacterium able to cause a disease. If you put a non pathogenic strain out there that happens to be sensitive, how does it result in the rise of a sensitive pathogen? Is it an existing pathogen that somehow loses its resistance in presence of a sensitive strain (there are no realistic scenarios where that could mechanistically happen, but it may not be obvious if you do not understand what antibiotics resistance actually is), or is it because the sensitive strain does the infection? That is the only possible route based on your own description, if a sensitive strain outcompetes other bacteria, including pathogens, what is there but those new strains to infect? However, a truely benign strain would not be infectious. Of course, if you actually sprayed folks with high titers, they may actually become dangerous. And of course nothing prevents those magic strains to actually acquire resistances (remember, Hypervalent iodine trying to tell you about acquired traits?).

And of course as everyone is also trying to tell you, it is impossible to replace microbiota with an artificial strain short of disinfecting every living being and the complete environment on top, which basically would collapse the whole ecosystem. It is just so monumentally, mindboggling silly, but apparently there is not way in to make you see that (as it would require to learn a bit about bacteria and other microbes in the first place). 

[StringJunky]

1 hour ago, mistermack said:

Charon, I think you are beyond help. The above does NOT imply that you are trying to infect a patient. The OP was perfectly clear. The tactic is to out-compete the resistant strains in the environment, with specially bred benign strains. 

If the patient DOES pick up an infection, then it's far more likely to be from one of the sensitive strain, which would be extremely easy to clear. But that's not the intention of the process. It's just something that could happen. 

The intention is to produce an environment that has ever lower numbers of the resistant strain, through competition for space in the environment.

Edit : Just to add to that, people are often put on antibiotic after an operation anyway, so the chances of getting infected by the sensitive strain, in those circumstances, would be close to nil.

Why does a person infected with the benign strain need it clearing?

The beauty of ignorance is that everything is so clear. You are not normally this persistent.

 

 

[CharonY]

4 minutes ago, StringJunky said:

Why does a person infected

And part of it is also not understanding language. Being infected and being colonized are two different types of events and have specific requirements. And could talk about cases where the difference between benign and harmful bacteria start to blur but that is a different discussion (though quite an interesting one).

[mistermack]

4 minutes ago, StringJunky said:

Why does a person infected with the benign strain need it clearing?

The beauty of ignorance is that everything is so clear. You are not normally this persistent.

It's benign in the sense of being easy to clear, using the cheapest and most widely used antibiotics. That's been made clear numerous times, in this thread, including the very first post. You could try a bit of reading before you dash off a post. I've called it many things, including sensitive, etc. In the OP I said "  A strain of the same bug that keels over at the slightest hint of the cheapest antibiotic. "

How hard can it be to get that concept? I said benign because I got bored repeating myself to people who don't read what they are posting about. 

You could try to breed a non-infective strain. That would be aiming too high, in my opinion.  

1 hour ago, CharonY said:

This refers back to the basic issue that you simply fail to understand basic microbiology.

It's you that can't even follow a simple post. You do it over and over again. It feels like being trolled, to be honest. I'm fed up with answering posts that are clearly not based on the OP or my replies.

1 hour ago, CharonY said:

An infection is caused by a pathogen, a specific bacterium able to cause a disease. If you put a non pathogenic strain out there that happens to be sensitive, how does it result in the rise of a sensitive pathogen?

You're as bad as string junky. Nobody said anything about a non-pathogenic strain. Did you even read the OP? You've posted enough times, but you still don't get it. I can't see how anyone can read the OP and fail to get what's being proposed. Whether it would work or not, is worth a discussion, but repeating the very simple concept over and over again to people who can't seem to even grasp the basic idea is tiresome.

[CharonY]

10 minutes ago, mistermack said:

got bored repeating myself to people

You could entertain yourself by educating yourself about what an infection is, and how antibotics resistances work. And apparently you also do not know what a non-infectious bacterium is, which indicates you probably do not know the difference between pathogens and non-pathogens. Of course you are repeating yourself, you simply have no information to improve your posts. You are also not reading what folks are telling you, as you just keep repeating and presenting your limited understanding of microbes. I am not sure what else to do than telling you that your basic premise flies into the face of basic microbiology there is simply not much to add.

Before I stop this futile exercise: what, do you imagine is a mechanism of antibiotics sensitivity? And how about you tell me at least one method of resistance? 

 

 

[mistermack]

1 minute ago, CharonY said:

Before I stop this futile exercise: what, do you imagine is a mechanism of antibiotics sensitivity? And how about you tell me at least one method of resistance? 

Why don't you either address the OP and stop trying to derail the thread, or open a thread on your suggested topic. As a moderator, you shouldn't be trying derails. 

As far as this thread goes, your attempts to appear an authority are not at all convincing, I've never fallen for your bluster. Your posts give you away because you get the wrong end of every stick. The condescending attitude just doesn't come off.

[sangui]

I like this idea: it's close to the phage therapy (wich is one of the funniest ways to fight an infection ever ^^).

However, I 'm pretty sure it would not work.
1 One of the biggest antibiotic resistance problems is the ability to be delivered by a plasmid. Our sensitive strain would have those plasmid and become resistant really soon. So we would get back in the original solution.

2 Place like hospitals NEED to be clean up often. If we had some strain (even really sensitive) it would kill a lot of people (Antibiotic doesn't cure every desease : resistance or not).

3 Instability: bacteria mutate, really often and it becomes a kind of a time bomb (some day it will be dangerous, and if you have more bacteria this day will come sooner.).

[StringJunky]

55 minutes ago, mistermack said:

It's benign in the sense of being easy to clear, using the cheapest and most widely used antibiotics. That's been made clear numerous times, in this thread, including the very first post. You could try a bit of reading before you dash off a post. I've called it many things, including sensitive, etc. In the OP I said "  A strain of the same bug that keels over at the slightest hint of the cheapest antibiotic. "

How hard can it be to get that concept? I said benign because I got bored repeating myself to people who don't read what they are posting about. 

You could try to breed a non-infective strain. That would be aiming too high, in my opinion.  

It's you that can't even follow a simple post. You do it over and over again. It feels like being trolled, to be honest. I'm fed up with answering posts that are clearly not based on the OP or my replies.

You're as bad as string junky. Nobody said anything about a non-pathogenic strain. Did you even read the OP? You've posted enough times, but you still don't get it. I can't see how anyone can read the OP and fail to get what's being proposed. Whether it would work or not, is worth a discussion, but repeating the very simple concept over and over again to people who can't seem to even grasp the basic idea is tiresome.

Has it occurred to you that you might be pursuing a train of thought which only makes sense to you but in reality can't fly and that's what charon and hyper are trying to relay to you.

1 hour ago, CharonY said:

And part of it is also not understanding language. Being infected and being colonized are two different types of events and have specific requirements. And could talk about cases where the difference between benign and harmful bacteria start to blur but that is a different discussion (though quite an interesting one).

I would associate 'benign' with colonizing and infection with pathogens.

[CharonY]

12 minutes ago, StringJunky said:

I would associate 'benign' with colonizing and infection with pathogens.

That is absolutely correct. There is much overlap on many of the mechanisms involved (e.g. nutritional acquisition, surface attachment etc.), though a rule of thumb is that if it is detrimental to the host we start thinking of something as an infection. As usual in biology, the boundaries are not fixed, and due to certain conditions (immune system issues, tissue injuries, but potentially also nutritional shifts etc.) otherwise benign bacteria may actually colonize areas where they start to do harm (i.e. they become opportunistic pathogens). To me, it is always interesting that in medicine we have these seemingly clear boundaries and treatment options, whereas the buggers themselves do not particularly care about them. There is this huge overlap between commensalism, beneficial symbiosis an parasitism with vastly different outcomes, but often fundamentally related mechanisms.

That being said, it is important to recognize differences when they matter, such as when thinking about treating infections.

[StringJunky]

1 hour ago, sangui said:

I like this idea: it's close to the phage therapy (wich is one of the funniest ways to fight an infection ever ^^).

However, I 'm pretty sure it would not work.
1 One of the biggest antibiotic resistance problems is the ability to be delivered by a plasmid. Our sensitive strain would have those plasmid and become resistant really soon. So we would get back in the original solution.

2 Place like hospitals NEED to be clean up often. If we had some strain (even really sensitive) it would kill a lot of people (Antibiotic doesn't cure every desease : resistance or not).

3 Instability: bacteria mutate, really often and it becomes a kind of a time bomb (some day it will be dangerous, and if you have more bacteria this day will come sooner.).

Yes, his idea is just adding to the potential infectious load in the long term. Also, his bred bacteria need to have some clear existential or reproductive advantage in the designated environmental niche that favours their presence over the pathogens, if they are to be useful in that regimen.

Edited October 22, 2019 by StringJunky

[mistermack]

1 hour ago, sangui said:

I like this idea: it's close to the phage therapy (wich is one of the funniest ways to fight an infection ever ^^).

However, I 'm pretty sure it would not work.
1 One of the biggest antibiotic resistance problems is the ability to be delivered by a plasmid. Our sensitive strain would have those plasmid and become resistant really soon. So we would get back in the original solution.

2 Place like hospitals NEED to be clean up often. If we had some strain (even really sensitive) it would kill a lot of people (Antibiotic doesn't cure every desease : resistance or not).

3 Instability: bacteria mutate, really often and it becomes a kind of a time bomb (some day it will be dangerous, and if you have more bacteria this day will come sooner.).

Thanks Sangui. But just to make it clear, the idea is not to stop the normal cleaning regime. You keep cleaning thoroughly and regularly as before, but each time afterwards you re-apply the antibiotic-sensitive strain afresh, by dusting or spraying, or whatever method has been developed as best. So the bugs you apply never get the time to mutate, or become resistant. They are constantly cleared away and renewed with new copies of the original strain. 

It wouldn't be hard to test for whether this works without using real live patients as guinea pigs. You could rig up a test room, spread around samples of the resistant bug, and re-test after a week of applying the process. Compare the results for frequency of the resistant strain after using the method, and not using it. If there was a real difference, it might be something worth pursuing. 

1 hour ago, StringJunky said:

Has it occurred to you that you might be pursuing a train of thought which only makes sense to you but in reality can't fly and that's what charon and hyper are trying to relay to you.

If they were the only people I'd mentioned it to, you might have a point. But people elsewhere have had no problem getting the principle, even if they don't think it would work. I'm dubious myself, I'm acting as advocate here, but the idea for me is to debate specific points that might make the process work or not work. 

7 minutes ago, StringJunky said:

Yes, his idea is just adding to the potential infectious load in the long term. Also, his bred bacteria need to have some clear existential or reproductive advantage in the designated environmental niche that favours their presence over the pathogens, if they are to be useful in that regimen.

No, for the same reason that I mentioned above. They only have to survive from one clean to the next. They then get cleaned away, and it's all re-applied afresh. 

[Phi for All]

5 minutes ago, mistermack said:

I'm dubious myself, I'm acting as advocate here, but the idea for me is to debate specific points that might make the process work or not work. 

!

Moderator Note

Then you need to stop grousing when those specific points are brought up by experts. If you can't do this civilly, then take a break from the site. If you want to act as an advocate, then listen to the folks who know this better than you. 

 

[Arete]

On 10/16/2019 at 3:48 PM, mistermack said:

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.

Artificial selection is not necessarily quicker than evolution, but using CRISPR Cas9 approaches, it is simple enough to produce antibiotic susceptible strains. 

On 10/16/2019 at 3:48 PM, mistermack said:

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.

Aseptic technique is still the most valuable tool in the prevention of nosocomical infection. Spreading pathogenic bacteria about an OR - drug susceptible or not, would have significant detrimental effects. 

On 10/16/2019 at 3:48 PM, mistermack said:

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.

So a few things

1) Often antibiotic resistance (AR) genes come with negligible costs to the bacteria, so do not suffer from negative selection. 

2) They are often encoded on extrachromosomal transposable genetic elements (e.g. plasmids) or like the MecA gene in Staphylococcus aureus can be transferred by viruses - so you cannot prevent the  spread of AR genes between your susceptible and resistant strains. 

3) AR genes often, through selfish gene mechanisms, get crowded onto plasmids or prophage with other genes that confer a net benefit, such that they can piggyback on the positive selection of other genes to proliferate. 

4) Resistance mechanisms like multi-drug efflux pumps, efflux many many other cytoplasmic contaminants, such they provided a benefit to bacteria in a wide array of environments. 

5) Over 80% of antibiotics produced in the developed world are used as growth promoters in agriculture, rather than therapeutics. Therefore most of the interaction between bacteria and antibiotics is happening in the broader environment, not in the clinic. 

6) Continuing from above, most of your patients present to the clinic having already acquired the resistant infection in the broader environment, so bacteria in the clinic are unlikely to have a positive impact. 

On 10/16/2019 at 3:48 PM, mistermack said:

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.

Dusting yourself with Staph/Klebsiella/Salmonella/Cholera etc, resistant or not is a terrible idea. You would wind up with far higher rates of infection and subsequent morbidity as a result, with a net negative public health outcome. 

[CharonY]

18 minutes ago, Arete said:

Artificial selection is not necessarily quicker than evolution, but using CRISPR Cas9 approaches, it is simple enough to produce antibiotic susceptible strains. 

Good points, though I would add that in contrast to resistance, susceptibility is a rather difficult concept. For the most part it is more the absence of a resistance mechanisms than a proper trait in itself. Beyond that, the ability to deal with antibiotic stress is highly dependent on factors such as nutritional status. I.e. a strain on minimal medium will be much more susceptible than in rich medium. Mutations associated with higher susceptibility will likely also result in lower viability and/or competitiveness.