Publication Date:
2014-01-11
Description:
Many bacterial pathogens cause persistent infections despite repeated antibiotic exposure. Bacterial persisters are antibiotic-tolerant cells, but little is known about their growth status and the signals and pathways leading to their formation in infected tissues. We used fluorescent single-cell analysis to identify Salmonella persisters during infection. These were part of a nonreplicating population formed immediately after uptake by macrophages and were induced by vacuolar acidification and nutritional deprivation, conditions that also induce Salmonella virulence gene expression. The majority of 14 toxin-antitoxin modules contributed to intracellular persister formation. Some persisters resumed intracellular growth after phagocytosis by naive macrophages. Thus, the vacuolar environment induces phenotypic heterogeneity, leading to either bacterial replication or the formation of nonreplicating persisters that could provide a reservoir for relapsing infection.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Helaine, Sophie -- Cheverton, Angela M -- Watson, Kathryn G -- Faure, Laura M -- Matthews, Sophie A -- Holden, David W -- 095484/Wellcome Trust/United Kingdom -- MR/K027077/1/Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2014 Jan 10;343(6167):204-8. doi: 10.1126/science.1244705.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of Microbiology, Medical Research Council Centre for Molecular Bacteriology and Infection, Imperial College London, Armstrong Road, London SW7 2AZ, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24408438" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Anti-Bacterial Agents/pharmacology
;
Antitoxins/genetics
;
Bacterial Toxins/genetics
;
Cefotaxime/pharmacology
;
Gene Deletion
;
Gene Expression Regulation, Bacterial
;
Lymph Nodes/immunology/microbiology
;
Macrophages/*microbiology
;
Mesentery/immunology/microbiology
;
Mice
;
Mice, Inbred BALB C
;
Mice, Inbred C57BL
;
Operon/genetics
;
Phagocytosis
;
Pyrophosphatases/genetics
;
Recurrence
;
Salmonella Infections/*immunology/*microbiology
;
Salmonella typhimurium/drug effects/genetics/*growth & development
;
Spleen/immunology/microbiology
;
Virulence
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
