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destroy penicillin-resistant bacteria
  [vote for,

Penicillin is an antibiotic which kills bacteria. Widely used in medicine
Bacteria develop resistance to penicillin. The most widespread method of resistance is to break down a crucial structural feature of the molecule, the beta-lactam ring. The enzymes which do this are often encoded on plasmids; small pieces of DNA which can spread between bacteria.

New derivatives of penicillin are made which bacteria are not resistant to, however they can often develop resistance fairly quickly, and this can spread to different pathogens via plasmids.
My idea is to develop a penicillin derivative which is not toxic to bacteria, however is a substrate for penicillinases. And the product of penicillinase attack would yield a compound with antimicrobial effects.

I imagine this could be done by having the beta-lactam ring cleavage product undergoing further intramolecular rearrangement to release a highly toxic molecule. But I am not a chemist so I don't know how feasible this is.
This compound could be administered along with penicillin or chased with penicillin, or just where penicillin-resistant bacteria outbreaks occur, whatever proves best.

Loris, May 09 2003

Background reading http://www.arches.u...2/pathogenesis.html
or just use google I suppose. [Loris, Oct 06 2004]


       If you could give a large enough dose, it wouldn't need to break down into something toxic, but it could simply slow the breakdown of penecillin by overwhelming the enzyme (so there would be enough more of this other compound that it inhibits the enzyme by outcompeting the penecillin for the active site, keeping it occupied). The problem with this idea would be that the compound itself could have some toxicity barring a high enough dose.   

       I'm in a drug design class :)
mandy, May 09 2003

       Most antibiotics affect good and bad bacteria alike. That's why it is recommended that you eat active-culture yogurt to replace to good bacteria while on antibiotics.
mandy, May 10 2003

       Mandy, perhaps you already know this but I'll just mention it since I should have done already.
The competitor inhibition/poisoning of penicillinase idea is already baked. A quick google search put up two: Amoxicillin plus clavulanic acid (combination is Augmentin), and tricardillin plus clavulanic acid (combination is Timentin).

       Toejam, as Mandy has said, many antibiotics kill a broad range of bacteria and not just the pathogens (disease-causing organisms). The compound I described, however, would not have this problem, because it would not generate a toxin until/unless it was attacked by penicillinase. So it would actually be better in this sense.   

       Unabubba, I'm not sure what you mean.
Would the drug have side-effects? Well ideally not, although of course most drugs do (including antibiotics).

       Thinking about this idea some more, probably if it were possible people would already have done it. I guess I am just not as inventive as I'd like.
Although I still like the idea. Such a compound would be really useful in genetic engineering as well as medicine.
Loris, May 12 2003

       <Childish Mood>
//I imagine this could be done by having the beta-lactam ring cleavage product// Ha ha you said cleavage. <points finger and laughs>
</Childish Mood>
silverstormer, May 12 2003

       Toejam, in brief, yes.
Believe it or not our bodies carry about ten times as many bacterial as 'human' cells. (Bacterial cells are much smaller though). These are carried both on the skin and in the guts. The vast majority of these bacteria don't cause disease; and indeed their presence can help exclude the disease-causers.

       In any case, penicillinases are proteins which inactivate penicillins. Most bacteria don't produce these, and are damaged and eventually killed by penicillin.
However, years of giving antibiotics to people has provided a selective pressure for bacteria which can survive in this environment. Bacteria which destroy penicillin have evolved, and for reasons I won't go into, this resistance can spread between different types of bacteria.
Why then are not all bacteria happily becoming antibiotic resistant? The reason is that producing the resistance apparatus costs effort, so these bacteria grow slightly slower than susceptible bacteria.
Thus, only those populations of bacteria which are constantly being treated with penicillin will accquire the resistance. These are usually the disease-causing bacteria. A few individuals in other environments will pick up resistances, but they are not selected for so it doesn't spread.
Loris, May 12 2003

traditional penicillins are active against susceptible E.coli strains - ie those which don't produce penicillinases. An anti-penicillinase antibiotic, if it worked, would not be. Therefore it would affect the gut microflora very much less than what is currently fairly routine treatment.

       You see this method is much more targeted - it attacks only penicillin-resistant bacteria, which are typically the ones you want to kill.   

       By the way, some plasmids are capable of transferring between and maintainance inside basically any Gram-negative bacteria (I have studied one group of these; the IncP-1 incompatibility group of plasmids). Such plasmids can pick up multiple antibiotic resistance 'cassettes' and thus confer multiple-drug-resistance into different species of bacteria. A benign bacterial community may confer some protection against invasion by pathogenic species, but probably won't halt antibiotic spread.
Loris, May 12 2003

       This is actually a really good idea, just somewhat difficult to implement. I hadn't looked it up, I was just spouting off stuff I learned in my class, and I'm not surprised it's baked since competetive inhibition is pretty easy. So, your compound would have to be: 1. fairly inert in the human body 2. be able to sit in the active site of beta-lactamase and be cleaved 3. the cleavage product would have to have bacteriocidal or bacteriostatic effects by blocking another enzyme within the bacteria 4. the product would either be non-toxic to human cells or be converting into a non-toxic entity before leaving the bacteria.   

       An interesting challenge. Too bad I already picked osteoarthritis to work on for my project, because I might have better luck with this one.
mandy, May 12 2003

       Good idea, and not baked. If made, this compound would be selective for the pencillinase producers - kind of like using heat seeking missiles: they only blow up things with engines, and leave your barefoot buddies alone.   

       The problem: what antibiotic will be released after the penicillinase does its job? There are a limited number of chemicals which are bad for the bugs but not bad for the people. If it is just some other existing, effective antibiotic, why not just use that antibiotic and forget all the nifty penicillinase bit. If it is penicillin, the penicillinase will get that too. If it is some as yet unknown antibiotic, I can make up an even better unknown antibiotic to invent. I call it Ubercillin.   

       You still get a breakfast burrito from me for the thought process.
bungston, May 12 2003


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