The Role of Host-Generated H(2)S in Microbial Pathogenesis: New Perspectives on Tuberculosis

For centuries, hydrogen sulfide (H(2)S) was considered primarily as a poisonous gas and environmental hazard. However, with the discovery of prokaryotic and eukaryotic enzymes for H(2)S production, breakdown, and utilization, H(2)S has emerged as an important signaling molecule in a wide range of physiological and pathological processes. Hence, H(2)S 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 H(2)S 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 H(2)S in microbial pathogenesis, which may lead to new virulence paradigms. Therefore, this review provides an overview of sulfide chemistry, enzymatic production of H(2)S, and the importance of H(2)S in metabolism and immunity in response to microbial pathogens. We then describe our current understanding of the role of host-derived H(2)S 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 H(2)S-donor compounds, inhibitors of H(2)S-producing enzymes, and their potential clinical significance.