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Saini 2020 Nat Commun

From Bioblast
Publications in the MiPMap
Saini V, Chinta KC, Reddy VP, Glasgow JN, Stein A, Lamprecht DA, Rahman MA, Mackenzie JS, Truebody BE, Adamson JH, Kunota TTR, Bailey SM, Moellering DR, Lancaster JR Jr, Steyn AJC (2020) Hydrogen sulfide stimulates Mycobacterium tuberculosis respiration, growth and pathogenesis. Nat Commun 11:557.

» PMID: 31992699 Open Access

Saini V, Chinta KC, Reddy VP, Glasgow JN, Stein A, Lamprecht DA, Rahman MA, Mackenzie JS, Truebody BE, Adamson JH, Kunota TTR, Bailey SM, Moellering DR, Lancaster JR Jr, Steyn AJC (2020) Nat Commun

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.

Bioblast editor: Plangger M O2k-Network Lab: US AL Birmingham Kraus DW, US AL Birmingham Moellering DR


Labels: MiParea: Respiration, Genetic knockout;overexpression, Pharmacology;toxicology  Pathology: Infectious 

Organism: Eubacteria 

Preparation: Intact cells 

Regulation: Substrate 

Pathway: CIV  HRR: Oxygraph-2k 

Labels, 2020-02