<i>Salmonella</i> persisters undermine host immune defenses during antibiotic treatment.

Abstract

Many bacterial infections are hard to treat and tend to relapse, possibly due to the presence of antibiotic-tolerant persisters. In vitro, persister cells appear to be dormant. After uptake of <i>Salmonella</i> species by macrophages, nongrowing persisters also occur, but their physiological state is poorly understood. In this work, we show that <i>Salmonella</i> persisters arising during macrophage infection maintain a metabolically active state. Persisters reprogram macrophages by means of effectors secreted by the <i>Salmonella</i> pathogenicity island 2 type 3 secretion system. These effectors dampened proinflammatory innate immune responses and induced anti-inflammatory macrophage polarization. Such reprogramming allowed nongrowing <i>Salmonella</i> cells to survive for extended periods in their host. Persisters undermining host immune defenses might confer an advantage to the pathogen during relapse once antibiotic pressure is relieved.