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Volume 170, Issue 5

Targeting pH-driven adaptation Open Access

Abstract

(Mtb) senses and adapts to host environmental cues as part of its pathogenesis. One important cue sensed by Mtb is the acidic pH of its host niche – the macrophage. Acidic pH induces widespread transcriptional and metabolic remodelling in Mtb. These adaptations to acidic pH can lead Mtb to slow its growth and promote pathogenesis and antibiotic tolerance. Mutants defective in pH-dependent adaptations exhibit reduced virulence in macrophages and animal infection models, suggesting that chemically targeting these pH-dependent pathways may have therapeutic potential. In this review, we discuss mechanisms by which Mtb regulates its growth and metabolism at acidic pH. Additionally, we consider the therapeutic potential of disrupting pH-driven adaptations in Mtb and review the growing class of compounds that exhibit pH-dependent activity or target pathways important for adaptation to acidic pH.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): environmental cues , Mycobacterium tuberculosis , pathogenesis and therapeutics
Funding
This study was supported by the:
  • AgBioResearch, Michigan State University
    • Principle Award Recipient: RobertB. Abramovitch
  • NIH-NIAID (Award R01AI116605)
    • Principle Award Recipient: RobertB. Abramovitch
© 2024 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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2024-05-08
2024-05-20
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http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.001458
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Targeting Mycobacterium tuberculosis pH-driven adaptation
Microbiology 170, 001458 (2024); https://doi.org/10.1099/mic.0.001458
/content/journal/micro/10.1099/mic.0.001458
/content/journal/micro/10.1099/mic.0.001458
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