Hydrogen sulfide stimulates Mycobacterium tuberculosis respiration, growth and pathogenesis

Academic Article

Abstract

  • Hydrogen sulfide (H S) is involved in numerous pathophysiological processes and shares overlapping functions with CO and •NO. However, the importance of host-derived H S in microbial pathogenesis is unknown. Here we show that Mtb-infected mice deficient in the H S-producing enzyme cystathionine β-synthase (CBS) survive longer with reduced organ burden, and that pharmacological inhibition of CBS reduces Mtb bacillary load in mice. High-resolution respirometry, transcriptomics and mass spectrometry establish that H S stimulates Mtb respiration and bioenergetics predominantly via cytochrome bd oxidase, and that H S reverses •NO-mediated inhibition of Mtb respiration. Further, exposure of Mtb to H S regulates genes involved in sulfur and copper metabolism and the Dos regulon. Our results indicate that Mtb exploits host-derived H S to promote growth and disease, and suggest that host-directed therapies targeting H S production may be potentially useful for the management of tuberculosis and other microbial infections. 2 2 2 2 2 2 2 2
  • Published In

    Digital Object Identifier (doi)

    Author List

  • Saini V; Chinta KC; Reddy VP; Glasgow JN; Stein A; Lamprecht DA; Rahman MA; Mackenzie JS; Truebody BE; Adamson JH
  • Volume

  • 11
  • Issue

  • 1