Salmonella persisters undermine host immune defenses during antibiotic treatment

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 species by macrophages, nongrowing persisters also occur, but their physiological state is poorly understoo...

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Bibliographic Details
Published inScience (American Association for the Advancement of Science) Vol. 362; no. 6419; pp. 1156 - 1160
Main Authors Stapels, Daphne A C, Hill, Peter W S, Westermann, Alexander J, Fisher, Robert A, Thurston, Teresa L, Saliba, Antoine-Emmanuel, Blommestein, Isabelle, Vogel, Jörg, Helaine, Sophie
Format Journal Article
LanguageEnglish
Published United States The American Association for the Advancement of Science 07.12.2018
Subjects
Animals
Anti-Bacterial Agents - pharmacology
Anti-Bacterial Agents - therapeutic use
Antibiotics
Cells, Cultured
Drug Resistance, Bacterial
Effectors
Environmental stress
Female
Genomic Islands
Host-Pathogen Interactions - immunology
Immune response
Immunity, Innate
Infections
Inflammation
Innate immunity
Macrophages
Macrophages - immunology
Macrophages - metabolism
Macrophages - microbiology
Mice
Mice, Inbred C57BL
Pathogenicity
Pathogens
Recurrence
Salmonella
Salmonella Infections - drug therapy
Salmonella Infections - immunology
Salmonella Infections - microbiology
Salmonella typhimurium - drug effects
Salmonella typhimurium - metabolism
Type III Secretion Systems - metabolism
Virulence
Virulence factors
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Summary: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 species by macrophages, nongrowing persisters also occur, but their physiological state is poorly understood. In this work, we show that persisters arising during macrophage infection maintain a metabolically active state. Persisters reprogram macrophages by means of effectors secreted by the pathogenicity island 2 type 3 secretion system. These effectors dampened proinflammatory innate immune responses and induced anti-inflammatory macrophage polarization. Such reprogramming allowed nongrowing 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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.aat7148