Ricerc@Sapienza

Hydrogen sulphide (H2S), as the other well-known gasotransmitter nitric oxide (NO), is a highly toxic gas that interferes with cellular respiration; however, at low physiological amounts, it plays an important role in cell signalling and in fuelling bioenergetics in mammals. The role of H2S in bacterial energy metabolism remains poorly investigated, notwithstanding the emerging link between energy production and pathogenesis. Remarkably, endogenously produced H2S has been recently recognized as a general protective molecule, which renders multiple bacterial species highly resistant to oxidative stress, various classes of antibiotics and host immune responses. Therefore, understanding the mechanisms underlying H2S-mediated resistance would help in developing new therapeutic strategies against human pathogens.

Relevant to pathophysiology, of the different enzymes synthesizing H2S in E.coli, 3-mercaptopyruvate sulfurtransferase (MST) appears crucial in the defence against hydrogen peroxide toxicity and in antimicrobials resistance. Hence, defects in its expression and function result in lower virulence. Moreover, MST has been recently related to the production of sulfane sulphur, reactive species currently thought to mediate the signalling and protective properties previously associated to free H2S. Our working hypothesis is that MST endows E.coli with the ability to successfully resist NO and derived species produced by the host to counteract infections.

This project aims at studying the involvement of bacterial H2S in the defence mechanisms against nitrosative stress and in energy metabolism using E.coli wild type and MST mutant strains as model system. Research will focus on the quantification of expression level and activity of enzymes as well as on the determination of viability, redox state and bioenergetic parameters of cells in response to NO/ H2S to better understand the role played by sulphide within the framework of host-microbe relationships.