Slow but steady wins the drug race

Bacteria that survive antibiotic assaults fall into two groups: resistant mutants; and the more mysterious persistent cells. Persisters, a known entity since 1944, survive the intial burst of antibiotics but unlike mutants may succumb to later treatments. Nathalie Balaban (now at Hebrew University, Jerusalem, Israel), Stanislas Leibler (Rockefeller University, New York, NY), and colleagues now find that persisters are a constant presence in the population—a slow-growing minority that acts as a reserve population in case of chemical attack.

The alternative explanations for persisters are legion. They might be completely dormant, or normal cells caught in a protected part of the cell cycle when the antibiotic arrives, or a state induced in response to antibiotic treatment. Balaban and colleagues looked at the behavior of single cells immobilized in a microfluidic device and saw that the few cells surviving antibiotic treatment were growing slowly even before the drug was added.

Extrapolating from the behavior of two mutants that produce an excess of persisters, the team deduced that wild-type cells make persisters both in response to time spent in stationary phase and at a constant rate during normal growth. Persisters escape their sluggish state at a slow but appreciable rate.

For basic researchers, the persistence pathway offers a bacterial example of an alternative phenotypic state, and one that is somehow generated at a low, constant frequency. For clinicians,the pathway may present a target for drugs that would get rid of the few bacteria left after conventional antibiotic treatments. ▪

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