Mycobacterium tuberculosis Responds to Chloride and pH as Synergistic Cues to the Immune Status of its Host Cell

The ability of Mycobacterium tuberculosis (Mtb) to thrive in its phagosomal niche is critical for its establishment of a chronic infection. This requires that Mtb senses and responds to intraphagosomal signals such as pH. We hypothesized that Mtb would respond to additional intraphagosomal factors t...

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Veröffentlicht in:	PLoS pathogens Jg. 9; H. 4; S. e1003282
Hauptverfasser:	Tan, Shumin, Sukumar, Neelima, Abramovitch, Robert B., Parish, Tanya, Russell, David G.
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	United States Public Library of Science 01.04.2013 Public Library of Science (PLoS)
Schlagworte:	Acidification Animals Anions Bacterial Proteins - metabolism Biology Bone Marrow Cells Cells, Cultured Cellular Microenvironment - physiology Chlorides - pharmacology Chlorine Gene Expression Regulation, Bacterial Host-bacteria relationships Hydrogen-Ion Concentration Immune response Interferon-gamma - genetics Macrophages - immunology Macrophages - microbiology Mice Mice, Inbred C57BL Mycobacterium tuberculosis Mycobacterium tuberculosis - drug effects Mycobacterium tuberculosis - immunology Mycobacterium tuberculosis - pathogenicity Mycobacterium tuberculosis - physiology Observations Pathogenesis Phagosomes - metabolism Phagosomes - microbiology Promoter Regions, Genetic Properties Studies Testing Tuberculosis Tuberculosis - microbiology United States
ISSN:	1553-7374, 1553-7366, 1553-7374
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Zusammenfassung:	The ability of Mycobacterium tuberculosis (Mtb) to thrive in its phagosomal niche is critical for its establishment of a chronic infection. This requires that Mtb senses and responds to intraphagosomal signals such as pH. We hypothesized that Mtb would respond to additional intraphagosomal factors that correlate with maturation. Here, we demonstrate that [Cl⁻] and pH correlate inversely with phagosome maturation, and identify Cl⁻ as a novel environmental cue for Mtb. Mtb responds to Cl⁻ and pH synergistically, in part through the activity of the two-component regulator phoPR. Following identification of promoters responsive to Cl⁻ and pH, we generated a reporter Mtb strain that detected immune-mediated changes in the phagosomal environment during infection in a mouse model. Our study establishes Cl⁻ and pH as linked environmental cues for Mtb, and illustrates the utility of reporter bacterial strains for the study of Mtb-host interactions in vivo.
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Conceived and designed the experiments: ST NS RBA DGR. Performed the experiments: ST NS. Analyzed the data: ST NS. Contributed reagents/materials/analysis tools: TP RBA. Wrote the paper: ST DGR. Current address: Michigan State University, Department of Microbiology and Molecular Genetics, East Lansing, Michigan, United States of America. The authors have declared that no competing interests exist.
ISSN:	1553-7374 1553-7366 1553-7374
DOI:	10.1371/journal.ppat.1003282