Ricerc@Sapienza

Hydrogen sulfide (H2S) is a gaseous signaling molecule which plays important roles in physiological and pathological processes. Notably, endogenously produced H2S has been recently recognized as a general protective molecule, which renders multiple bacterial species highly resistant to oxidative stress, host immune responses and antibiotics. Therefore, understanding the mechanisms underlying H2S-mediated resistance would help in developing new therapeutic strategies against human pathogens and antibiotic resistance, a serious public health problem worldwide.

In E.coli, H2S is enzimatically produced by 3-mercaptopyruvate sulfurtransferase (3MST), an enzyme belonging to the family of the sulfurtransferases. In addition to H2S production, the 3-MST contribute to the production of H2S-derived species, persulfides and polysulfides, which have an important cellular protection from oxidants. Remarkably, this enzyme appears crucial in the defence against hydrogen peroxide and in antimicrobial resistance in E. coli, including clinical pathogenic strains.
Our working hypothesis is that MST endows E.coli with the ability to successfully resist nitric oxide and its derived species which are produced by the host macrophages to counteract infections.

In this project I will study the role of MST in the bacterial response to nitrosative stress by using E.coli wild type and MST mutant strains to understand the molecular mechanisms that drive cytoprotection in E.coli, and possibly other pathogens, under stress conditions allowing survival, growth and host colonization.
By elucidating these mechanisms, I will contribute to the understanding of the bacterial strategies to combat host chemical weapons as well as the role of sulfide and its derived species within the framework of host-microbe relationships.