Mutations Buff Up Drug-Resistant Bugs

Antibiotic resistance has been a mixed blessing for bacteria, as the mutations that enable a bug to survive a drug also often disable some key cellular function or slow its growth. Now scientists have found that other mutations can fortify a drug-resistant bacteria without hindering its drug resistance. The finding, reported in tomorrow's Proceedings of the National Academy of Sciences, raises the concern that it may be tougher than previously thought to fight drug-resistant strains.

With drug-resistant strains running rampant, a few hospitals have limited use of certain antibiotics for months at a time--on the assumption that hardier drug-sensitive strains would outcompete the resistant bugs and allow the drugs to be effective once again. Although this has worked in a few cases--with penicillin, for instance--in many other experiments drug-resistant bacteria survive and continue to be a problem, says Dan Andersson, a microbiologist at the Swedish Institute for Infectious Disease Control in Uppsala.

To see if new mutations helped resistant strains grow stronger, Andersson and his colleagues infected mice with Salmonella typhimurium, which causes food poisoning. They injected drug-resistant salmonella, which grow much more slowly than sensitive strains, into the stomachs of the mice. After 12 to 24 days, genetic sequencing revealed that some resistant bacteria had developed mutations that had accelerated their growth rate to equal that of drug-sensitive strains. More importantly, these fast-growing resistant strains easily outcompeted the drug-sensitive ones when injected into mice in equal doses.

The finding suggests that resistant strains may permanently dominate sensitive ones, says Bruce Levin, a microbiologist at Emory University in Atlanta: "It makes the future look a little more bleak."

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