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

Date Published: April 4, 2013

Publisher: Public Library of Science

Author(s): Shumin Tan, Neelima Sukumar, Robert B. Abramovitch, Tanya Parish, David G. Russell, William R. Bishai.


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.

Partial Text

Mycobacterium tuberculosis (Mtb) causes a chronic infection in approximately one third of the human population and remains an important public health problem [1]. The macrophage (MØ) is the major host cell for much of Mtb’s life cycle, and a defining feature of Mtb’s pathogenesis is its ability to arrest full maturation of the phagosome in which it resides [2], [3]. Indeed, Mtb mutants that fail to arrest phagosomal maturation have reduced survival during MØ infection [4]. However, Mtb remains subject to multiple stresses within the phagosome, which may act as important environmental cues for Mtb [5]. Proper sensing of such signals informs Mtb of its surroundings, allowing the bacterium to respond appropriately to ensure its survival and replication. Elucidating the cues that Mtb recognizes during infection, and the possible interplay between such signals, is critical for a complete understanding of the impact of the microenvironment on Mtb pathogenesis and persistence, and Mtb’s interaction with fundamental host cell processes.




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