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Science. 2018 Dec 7;362(6419):1156-1160. doi: 10.1126/science.aat7148.

Salmonella persisters undermine host immune defenses during antibiotic treatment.

Author information

1
MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, UK.
2
Institute of Molecular Infection Biology, University of Würzburg, Würzburg, Germany.
3
Helmholtz Institute for RNA-based Infection Research, Würzburg, Germany.
4
MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, UK. s.helaine@imperial.ac.uk.

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.

PMID:
30523110
DOI:
10.1126/science.aat7148
[Indexed for MEDLINE]
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