Persisters unmasked

Intracellular toxins cause bacterial growth arrest and antibiotic tolerance Penicillin may have saved more human lives than any other drug. Yet, almost as soon as it was introduced in the 1940s, researchers found that the antibiotic could not completely sterilize a culture of a Staphylococcus aureus strain sensitive to the drug ( 1 ). Shortly thereafter, Joseph Bigger showed that when the few cells that had survived an initial treatment were regrown in the absence of penicillin and then exposed again to the antibiotic, the proportion of survivors was similar to that found after the first treatment (see the first figure). Therefore, the survivors were not stable drug-resistant mutants, but transient drug-tolerant persisters ( 2 ). In the past decade, a resurgence of interest in persisters has revealed some of the molecular mechanisms that stimulate their formation. It has become clear that intracellular toxins present in virtually all bacteria control reversible bacterial growth arrest, explaining their antibiotic tolerance.