Bacteria that resist antibiotics are a growing problem worldwide, but one we thought we could limit or even reverse by better control of the drugs. This may be a forlorn hope: Some bacteria that have never seen an antibiotic can evolve resistance, and even thrive on it.

Bacteria usually become resistant if they're exposed to drug levels too low to kill them off, but high enough to favor the survival of resistant mutants. Such resistance is growing and could make TB and other diseases untreatable again.

The prevailing notion was that bacteria acquire and maintain resistance genes at a cost. So by carefully controlling antibiotics, resistance should not emerge by itself - and should die out as soon as the antibiotic is withdrawn and resistance is no longer an advantage.

Maybe not. Olivier Tenaillon, at Denis Diderot University, Paris, and colleagues were studying bacterial evolution by exposing Escherichia coli to high temperatures and little food. Unexpectedly, some bacteria spontaneously became resistant to the antibiotic rifampicin, even though they had never encountered it. The mutation that helped them deal with environmental stress just happened to confer resistance to the drg, used to treat TB and meningitis.

"Our work suggests that selective pressure other than antibiotics may drive resistance," says Tenaillon.

Moreover, bacteria with the mutation grew 20 percent faster than otherwise-identical bacteria - a first for a resistance mutation.

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It only had this beneficial effect in the heat-adapted strain, says Arjan de Visser, of Wageningen University in the Netherlands, who was not involved in the study. But, he adds, "these results are a cautionary tale for the use of antibiotics - resistance may come without costs (to bacteria)."

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