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Dual action antibiotic could make bacterial resistance nearly impossible

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Re: Dual action antibiotic could make bacterial resistance nearly impossible

#4

It’s unclear why the same benefit couldn’t be achieved by mixing two traditional antibiotics with different mechanisms of action. Maybe the combined dosage would stress the liver too much?

Bacteria can develop resistance to individual antibiotic mechanism. Then two strains can swap resistance genes to produce a super-bug: https://asm.org/articles/2023/january/plasmids-and-the-sprea...

My understanding is that in this case bacteria would have to develop resistance to two mechanisms at the same time, which is much more difficult.

Mandatory quote: "Life, uh, finds a way"

Re: Dual action antibiotic could make bacterial resistance nearly impossible

#5
post #4

It’s unclear why the same benefit couldn’t be achieved by mixing two traditional antibiotics with different mechanisms of action. Maybe the combined dosage would stress the liver too much?

Bacteria can develop resistance to individual antibiotic mechanism. Then two strains can swap resistance genes to produce a super-bug: https://asm.org/articles/2023/january/plasmids-and-the-sprea... My understanding is that in this case bacteria would have to develop resistance to two mechanisms at the same time, which is much more difficult. Mandatory quote: "Life, uh, finds a way"

Isn't it exactly the same situation? In one case you have two substances that attack cells by two different mechanisms, and in the other you have a single substance that attacks cells by two different mechanisms. In either case a strain that doesn't have resistance to both mechanisms will get wiped out, since just one of them destroys the cells or prevents them from reproducing. Even if some sub-strains develop resistance to one of the mechanisms, it won't matter because they will get wiped out by the other.

Re: Dual action antibiotic could make bacterial resistance nearly impossible

#6
post #4

Earlier quoted context omitted.

Bacteria can develop resistance to individual antibiotic mechanism. Then two strains can swap resistance genes to produce a super-bug: https://asm.org/articles/2023/january/plasmids-and-the-sprea... My understanding is that in this case bacteria would have to develop resistance to two mechanisms at the same time, which is much more difficult. Mandatory quote: "Life, uh, finds a way"

Isn't it exactly the same situation? In one case you have two substances that attack cells by two different mechanisms, and in the other you have a single substance that attacks cells by two different mechanisms. In either case a strain that doesn't have resistance to both mechanisms will get wiped out, since just one of them destroys the cells or prevents them from reproducing. Even if some sub-strains develop resis…

I'm not a biologist, but I'm guessing that having the concentrations of two antibiotics peak at the same time etc is much much trickier than having one molecule with two mechanisms of effect. Thus in actual (not perfect) use you end up with both effects active within a bacterium at one time, rather than potentially having some distance between the peaks.

From the article, it does look like they're smushing two antibiotic active sites into one molecule, so it seems a somewhat similar idea

Re: Dual action antibiotic could make bacterial resistance nearly impossible

#7
post #4

Earlier quoted context omitted.

Bacteria can develop resistance to individual antibiotic mechanism. Then two strains can swap resistance genes to produce a super-bug: https://asm.org/articles/2023/january/plasmids-and-the-sprea... My understanding is that in this case bacteria would have to develop resistance to two mechanisms at the same time, which is much more difficult. Mandatory quote: "Life, uh, finds a way"

Isn't it exactly the same situation? In one case you have two substances that attack cells by two different mechanisms, and in the other you have a single substance that attacks cells by two different mechanisms. In either case a strain that doesn't have resistance to both mechanisms will get wiped out, since just one of them destroys the cells or prevents them from reproducing. Even if some sub-strains develop resis…

But if doctors don’t always prescribe these two antibiotics to be used in tandem, then microbes will have an opportunity to evolve resistance to each one in isolation, putting those resistant genes out in the world. Whereas in this case, any bacteria ever encountering this drug will be hit by both mechanisms at once.

Re: Dual action antibiotic could make bacterial resistance nearly impossible

#8
post #4

Earlier quoted context omitted.

Bacteria can develop resistance to individual antibiotic mechanism. Then two strains can swap resistance genes to produce a super-bug: https://asm.org/articles/2023/january/plasmids-and-the-sprea... My understanding is that in this case bacteria would have to develop resistance to two mechanisms at the same time, which is much more difficult. Mandatory quote: "Life, uh, finds a way"

Isn't it exactly the same situation? In one case you have two substances that attack cells by two different mechanisms, and in the other you have a single substance that attacks cells by two different mechanisms. In either case a strain that doesn't have resistance to both mechanisms will get wiped out, since just one of them destroys the cells or prevents them from reproducing. Even if some sub-strains develop resis…

The antibacterial resistance is often on small DNA loops called plasmids which are often and easily exchanged between bacterial species. I assume this has to do with that, either the resistance would have to develop twice in the main genome or twice on the same plasmid.

In the normal dual antibacterial cases just developing a single resistance and acquiring the right plasmid is enough.

Re: Dual action antibiotic could make bacterial resistance nearly impossible

#9
post #4

Earlier quoted context omitted.

Bacteria can develop resistance to individual antibiotic mechanism. Then two strains can swap resistance genes to produce a super-bug: https://asm.org/articles/2023/january/plasmids-and-the-sprea... My understanding is that in this case bacteria would have to develop resistance to two mechanisms at the same time, which is much more difficult. Mandatory quote: "Life, uh, finds a way"

Isn't it exactly the same situation? In one case you have two substances that attack cells by two different mechanisms, and in the other you have a single substance that attacks cells by two different mechanisms. In either case a strain that doesn't have resistance to both mechanisms will get wiped out, since just one of them destroys the cells or prevents them from reproducing. Even if some sub-strains develop resis…

Good question. Take many many antibacterial molecules to kill a bacteria, so there are two plausible methods. The first is that two compounds can have different pharmacokinetics. That is to say, they move through the body in different ways and have different concentration profiles.

The second is about how they are used. Two separate compounds with the same pharmacokinetics could be effective if you use them in parallel, but you have to contend with the fact that real human users may not always use them that way. If two different companies make compound a and compound B, it is virtually impossible to prevent someone somewhere from using them separately

Re: Dual action antibiotic could make bacterial resistance nearly impossible

#10

It’s unclear why the same benefit couldn’t be achieved by mixing two traditional antibiotics with different mechanisms of action. Maybe the combined dosage would stress the liver too much?

Last year I was hospitalized and quarantined for Tuberculosis, which is fairly strong against antibiotics so the antibiotic therapy is 6 months long (minimum), and that's precisely how I was treated, by combining first 4 then 2 antibiotics in order to prevent the bacteria from developing resistance, but you're right, it's super bad for your liver, I've seen heavy alcoholic patients in the same ward that were refused treatment because "we would destroy your barely functioning liver and kill you", and watched them just die, but I don't think it completely prevents the bacteria from building resistance, it just minimizes the odds to a significant degree.
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