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Host-pathogen redox dynamics modulate Mycobacterium tuberculosis pathogenesis

Journal

PATHOGENS AND DISEASE
Volume 76, Issue 5, Pages -

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/femspd/fty036

Keywords

redox; dormancy; Dos; WhiB; tuberculosis; virulence

Funding

  1. NIH [R01Al111940, R21A127182]
  2. Bill and Melinda Gates Foundation Award [OPP1130017]
  3. CFRB, and Infectious Diseases and Global Health and Vaccines Initiative
  4. South African Medical Research Council
  5. National Institute of General Medical Sciences (NIGMS) Medical Scientist Training Program (MSTP) [T32GM008361]
  6. UAB CFAR [NIH P30 AI027767]

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Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, encounters variable and hostile environments within the host. A major component of these hostile conditions is reductive and oxidative stresses induced by factors modified by the host immune response, such as oxygen tension, NO or CO gases, reactive oxygen and nitrogen intermediates, the availability of different carbon sources and changes in pH. It is therefore essential for Mtb to continuously monitor and appropriately respond to the microenvironment. To this end, Mtb has developed various redox-sensitive systems capable of monitoring its intracellular redox environment and coordinating a response essential for virulence. Various aspects of Mtb physiology are regulated by these systems, including drug susceptibility, secretion systems, energy metabolism and dormancy. While great progress has been made in understanding the mechanisms and pathways that govern the response of Mtb to the host's redox environment, many questions in this area remain unanswered. The answers to these questions are promising avenues for addressing the tuberculosis crisis.

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