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Salmonella persisters undermine host immune defenses during antibiotic treatment

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Science  07 Dec 2018:
Vol. 362, Issue 6419, pp. 1156-1160
DOI: 10.1126/science.aat7148

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Actively persistent Salmonella

A proportion of Salmonella cells can enter a reversible state of growth arrest, which allows them to tolerate environmental stress such as antibiotics. Stapels et al. found that these cells are not dormant but are actively modulating their environment. Salmonella within their host macrophage niche deployed a specialized type 3 secretory system called SPI-2 to deliver virulence factors, including SteE, into host cells. SteE changed the cytokine profile of the infected macrophages to reprogram them into a noninflammatory and infection-permissive state. Thus, when antibiotics were removed, the Salmonella could reemerge and cause disease.

Science, this issue p. 1156

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 Salmonella species by macrophages, nongrowing persisters also occur, but their physiological state is poorly understood. In this work, we show that Salmonella persisters arising during macrophage infection maintain a metabolically active state. Persisters reprogram macrophages by means of effectors secreted by the Salmonella pathogenicity island 2 type 3 secretion system. These effectors dampened proinflammatory innate immune responses and induced anti-inflammatory macrophage polarization. Such reprogramming allowed nongrowing Salmonella 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.

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