[SCAN] How do metalloenzymes help Clostridium difficile during infection?

Title: How do metalloenzymes help Clostridium difficile during infection?

Speaker: Filipe Folgosa

Abstract: Clostridium difficile is the most prevalent pathogen among all healthcare-associated infections. This anaerobic bacterium can colonize the human gut, typically following agents that disrupt the normal gut microbiota, like antibiotics. In the gut, C. difficile is subjected to variable concentrations of oxygen, which it has to eliminate for survival. Its genome encodes for several proteins that should be capable to tackle the effects of oxygen as well as its derived reactive species. This group of proteins includes different types of flavodiiron proteins (FDPs), reverse rubrerithryns and catalases.

Our goal is to understand the biochemical rational behind this capacity and to clarify how these proteins work together in the cellular context, enabling C. difficile infection.

Extensive biochemical, redox and spectroscopic studies demonstrated that the non-canonical FDP acts preferentially as an oxygen reductase, receiving electrons directly from NADH precluding the need for extra partners, whereas the canonical FDP does not present a clear substrate specificity. On the other hand, as expected, the two reverse-rubrerithryns presented higher activity towards hydrogen peroxide.

Similar biochemical analyses were performed in cellular extracts of wild type and of multiple deletion mutant strains in order to understand the effect of each protein in the entire cellular metabolism when exposed to oxygen, as well as of one of its transcriptional regulator.