Deliberate Resistance

Monday, April 01, 1996
In the bacterial world, necessity seems to be the mother of mutation. Genetic mutation in an organism had always been thought to be an essentially random process. But within the past few years, researchers have found that starving E. coli can increase their mutation rate, thus increasing their chances of undergoing an adaptive mutation that will allow them to eat some otherwise indigestible food. Now microbiologist Joel Weiner and molecular geneticist Susan Rosenberg of the University of Alberta report that perfectly well fed bacteria may use the same strategy to develop resistance to antibiotics.

Citrobacter freundii, the bug they studied, causes a host of infections of the lung, bladder, and stomach. Normally it is vulnerable to penicillin. But there are strains of citrobacter that have the ability to resist a class of penicillin drugs called cephalosporins--because they have undergone mutations that allow them to crank out unusually large amounts of an enzyme, beta-lactamase, that degrades the drugs. The resistant strains first arose, Weiner says, when serious outbreaks of citrobacter among hospital patients were treated with large doses of cephalosporins.

In laboratory experiments, Weiner and Rosenberg found evidence that the resistance-conferring mutations happen only in citrobacter that are equipped with a functioning set of DNA-recombining enzymes--the same enzymes E. coli use to up their mutation rate. Bacteria without the enzymes die when they’re put in a nutrient solution containing cephalosporin; but some of the bacteria with the enzymes make the mutation they need, start churning out the beta-lactamase, and survive. Somehow, Weiner thinks, the presence of the antibiotic outside the bacterial cell wall must trigger the bacterium to start recombining DNA. Our results suggest that bacteria possess the ability to alter their mutation rate in response to any kind of stress that interferes with their ability to grow, Weiner says. Whether that ability may account for some of the current increase in antibiotic- resistant bacterial strains--a major problem in medicine these days--is not yet clear.
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