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

PLoS Pathogens

David G. Russell¹  Robert B. Abramovitch¹  Neelima Sukumar¹  Shumin Tan¹  Tanya Parish² 

[1] Cornell University, College of Veterinary Medicine, Department of Microbiology and Immunology, Ithaca, New York, United States of America;Infectious Disease Research Institute, and Department of Global Health, University of Washington School of Medicine, Seattle, Washington United States of America

关键词: Mycobacterium tuberculosis;    Phagosomes;    Immune response;    Confocal microscopy;    Gene expression;    Phagocytosis;    Infection imaging;    Microarrays;   

DOI  :  10.1371/journal.ppat.1003282

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY