Hydrogen sulfide stimulates Mycobacterium tuberculosis respiration, growth and pathogenesis.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31992699.
- Also identified by DOI 10.1038/s41467-019-14132-y and PMC identifier 6987094.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Hydrogen sulfide (H<sub>2</sub>S) is involved in numerous pathophysiological processes and shares overlapping functions with CO and •NO. However, the importance of host-derived H<sub>2</sub>S in microbial pathogenesis is unknown. Here we show that Mtb-infected mice deficient in the H<sub>2</sub>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<sub>2</sub>S stimulates Mtb respiration and bioenergetics predominantly via cytochrome bd oxidase, and that H<sub>2</sub>S reverses •NO-mediated inhibition of Mtb respiration. Further, exposure of Mtb to H<sub>2</sub>S regulates genes involved in sulfur and copper metabolism and the Dos regulon. Our results indicate that Mtb exploits host-derived H<sub>2</sub>S to promote growth and disease, and suggest that host-directed therapies targeting H<sub>2</sub>S production may be potentially useful for the management of tuberculosis and other microbial infections.
Medical subject headings
- Hydrogen Sulfide
- Mycobacterium tuberculosis