Hydrogen sulfide stimulates Mycobacterium tuberculosis respiration, growth and pathogenesis

Vikram Saini, Krishna C. Chinta, Vineel P. Reddy, Joel N. Glasgow, Asaf Stein, Dirk A. Lamprecht, Md. Aejazur Rahman, Jared S. Mackenzie, Barry E. Truebody, John H. Adamson, Tafara T. R. Kunota, Shannon M. Bailey, Douglas R. Moellering, Jack R. Lancaster and Adrie J. C. Steyn ()
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Vikram Saini: University of Alabama at Birmingham
Krishna C. Chinta: University of Alabama at Birmingham
Vineel P. Reddy: University of Alabama at Birmingham
Joel N. Glasgow: University of Alabama at Birmingham
Asaf Stein: University of Alabama at Birmingham
Dirk A. Lamprecht: Africa Health Research Institute
Md. Aejazur Rahman: Africa Health Research Institute
Jared S. Mackenzie: Africa Health Research Institute
Barry E. Truebody: Africa Health Research Institute
John H. Adamson: Africa Health Research Institute
Tafara T. R. Kunota: Africa Health Research Institute
Shannon M. Bailey: University of Alabama at Birmingham
Douglas R. Moellering: University of Alabama at Birmingham
Jack R. Lancaster: University of Pittsburgh School of Medicine
Adrie J. C. Steyn: University of Alabama at Birmingham

Nature Communications, 2020, vol. 11, issue 1, 1-17

Abstract: Abstract Hydrogen sulfide (H2S) is involved in numerous pathophysiological processes and shares overlapping functions with CO and •NO. However, the importance of host-derived H2S in microbial pathogenesis is unknown. Here we show that Mtb-infected mice deficient in the H2S-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 H2S stimulates Mtb respiration and bioenergetics predominantly via cytochrome bd oxidase, and that H2S reverses •NO-mediated inhibition of Mtb respiration. Further, exposure of Mtb to H2S regulates genes involved in sulfur and copper metabolism and the Dos regulon. Our results indicate that Mtb exploits host-derived H2S to promote growth and disease, and suggest that host-directed therapies targeting H2S production may be potentially useful for the management of tuberculosis and other microbial infections.

Date: 2020
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DOI: 10.1038/s41467-019-14132-y

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