The Role of Host-Generated H2S in Microbial Pathogenesis: New Perspectives on Tuberculosis.

Md Aejazur Rahman,Jack R Lancaster,Joel N Glasgow,Vineel P Reddy,Sajid Nadeem,Adrie J C Steyn,Ritesh R Sevalkar

doi:10.3389/fcimb.2020.586923

Abstract

For centuries, hydrogen sulfide (H2S) was considered primarily as a poisonous gas and environmental hazard. However, with the discovery of prokaryotic and eukaryotic enzymes for H2S production, breakdown, and utilization, H2S has emerged as an important signaling molecule in a wide range of physiological and pathological processes. Hence, H2S is considered a gasotransmitter along with nitric oxide (•NO) and carbon monoxide (CO). Surprisingly, despite having overlapping functions with •NO and CO, the role of host H2S in microbial pathogenesis is understudied and represents a gap in our knowledge. Given the numerous reports that followed the discovery of •NO and CO and their respective roles in microbial pathogenesis, we anticipate a rapid increase in studies that further define the importance of H2S in microbial pathogenesis, which may lead to new virulence paradigms. Therefore, this review provides an overview of sulfide chemistry, enzymatic production of H2S, and the importance of H2S in metabolism and immunity in response to microbial pathogens. We then describe our current understanding of the role of host-derived H2S in tuberculosis (TB) disease, including its influences on host immunity and bioenergetics, and on Mycobacterium tuberculosis (Mtb) growth and survival. Finally, this review discusses the utility of H2S-donor compounds, inhibitors of H2S-producing enzymes, and their potential clinical significance.

Highlights

Hydrogen sulfide (H2S) was not discovered until 1777 by the Swedish-German chemist Carl Wilhelm Scheele (Mitchell and Davenport, 1924), the description of its biological effects dates to the early 1700s, when Italian physician Bernardino Ramazzini (1633–1714) published his collection of observations regarding workers, their work environments, and occupationassociated illnesses as De Morbis Artificum Diatriba [Treatise on Worker’s Diseases]
Given the numerous studies that followed the discovery of iNOS (Nos2) and the importance of NO bioactivity in microbial pathogenesis (MacMicking et al, 1997b; Das et al, 2010), we anticipate a rapid increase in studies that further define the importance of H2S in microbial pathogenesis
This is intriguing, because to the best of our knowledge, the mortality of other knockout mice infected with Mycobacterium tuberculosis (Mtb) has been unchanged or increased compared to wild-type controls

Summary

Introduction

Hydrogen sulfide (H2S) was not discovered until 1777 by the Swedish-German chemist Carl Wilhelm Scheele (Mitchell and Davenport, 1924), the description of its biological effects dates to the early 1700s, when Italian physician Bernardino Ramazzini (1633–1714) published his collection of observations regarding workers, their work environments, and occupationassociated illnesses as De Morbis Artificum Diatriba [Treatise on Worker’s Diseases]. Three enzymes are responsible for the majority of H2S production in mammals: cystathionine g-lyase (CSE), cystathionine b-synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (3-MST). Another source of endogenous H2S is acid labile pools, which function in the presence of endogenous reductants and gut microbiota (Flannigan et al, 2011; Kimura, 2011). H2S is membrane-permeable and diffuses through cells (Mathai et al, 2009); it can act as a signaling molecule and/or interact directly with intracellular biomolecules

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