Internalization of Salmonella by Macrophages Induces Formation of Nonreplicating Persisters

Persistent Survival The role of persister cells—dormant cells that survive multidrug treatment—in the context of bacterial pathogenesis has not been explored in depth. Using a single-cell fluorescent dilution technique, Helaine et al. (p. 204 ) examined Salmonella Typhimurium persister-cell formation in vitro and in infections in mice. Within 30 min after phagocytosis by macrophages, Salmonella cells follow one of two fates, either to replication and generation of virulence effectors or to remaining viable but become nonreplicating persisters. Salmonella living within a macrophage vacuole are exposed to potentially stressful conditions that induce the expression of 14 Type II toxin-antidote loci in a ppGpp/lon protease-dependent manner, and this system appears to play a role in both virulence factor induction and persister-cell formation. The nonreplicating bacteria represent at least four distinct subpopulations, as defined by their ability to resume growth and their metabolic activity, but different phenotypes are observed in different pathogens and Escherichia coli persisters are distinct from Salmonella persisters.