antibiotic research

[kozz]

usually I hear of this or that new antibiotic being discovered in nature, and how they are being vigorously sought out in species-rich environments like rainforests.

There's plenty of undiscovered species with potential, but it seems like a lot of rocks have to be looked under before anything useful is found.

Is anyone trying to "engineer" antibiotics by stressing a population of some quick-evolving organism? Meaning, for a drug-resistant microbe, find a competitor species and a way to drive that species nearly to extermination vs the target microbe, but keep it barely viable; and see if the competitor species comes up with any clever ways to combat the virulent one. Such as manufacturing a new antibiotic.

This would accelerate the process that makes the antibiotics in nature. And they would be custom-made to attack a specific germ. Instead of sifting through thousands of possibilities and testing each for effectiveness.

Has anyone created a "designer antibiotic?" Tried to? Considered it?

[mith]

why not just create a very faulty polymerase to speed up evolution?

[MrMistery]

people have tried to create designer antibiotics, just like they have tried to create other designer drugs by looking at the structure of the target enzyme. Unfortunately, so far, rational drug design just doesn't work.

Unfortunately now most drugs are not made from natural compounds anymore, they are made by screening libraries of thousands of compounds that have been randomly synthesized. Hence the current crysis for new blockbuster drugs.

[JackBean]

MrMistery:
1) drugs are also searched from natural sources like new plant species
2) just recently has czech scientists found new cure to AIDS being some completely synthetic compound

[MrMistery]

1) Yes, but the big pharma companies are putting the vast majority of their money in the automated method, not in looking for natural compounds.

2) Do you have a peer-reviewed source for that? I tend to be skeptical

[JackBean]

Also natural sources can be searched automatically.

I'll try to find something.

[JackBean]

Here is it
http://pubs.acs.org/doi/abs/10.1021/jm9 ... istoryKey=
Rezacova P: Design of HIV Protease Inhibitors Based on Inorganic Polyhedral Metallacarboranes, J. Med. Chem., 2009, 52 (22), pp 7132–7141
http://pubs.acs.org/doi/pdf/10.1021/jm9011388
http://pubs.acs.org/doi/pdfplus/10.1021/jm9011388

[MrMistery]

developing an inhibitor for a protease is different from curing a disease. that may sound promising, but HIV protease inhibitors already exist, and obviously we still have AIDS around. While that may be an important achievement chemically (I can't read ACS papers to save my life), it may not even work as a drug against AIDS (you never know until you do a chemical trial), it might have too severe side effects (death) or even if it works perfectly, it would still face the resistance problem that all other HIV drugs face

[mkwaje]

I once read that you can observe evolution when you stare at it long enough. A group of scientists found out that after 31,500 generations, evolution took place.Similarly, I find it intriguing if we force a bacteria to adapt to form an antibiotic against human pathogens.

The most likely step is to select a fearsome pathogen and select a potential multiresistant non pathogenic bacteria, say E. coli. Then lets say we want to produce something against MRSA. Its like we're trying to make E. coli evolve a new set of genes. Would you rather do that? Wait for thousands of attempts (and maybe not getting anything at all) or take your chance to look under a rock for novel organisms with never-before-seen enzyme systems. At least this time, you have more organisms to play around with and maybe unintentionally discovering some other useful antibiotic/enzyme/system.

Just my two cents.

[JackBean]

You don't need so long evolution to take place. There are plenty of examples, when the evolution was quite fast