P-373 - RIC -A family of proteins that repair cellular damage caused by oxidative/nitrosative stress

Abstract

Microorganisms are exposed to harmful oxygen and nitrogen reactive species that are formed in the environment and produced by cells of the mammalian innate immunity. Iron-sulfur clusters, contained in proteins that largely sustain microbial life, are damaged by oxidative/nitrosative stresses causing the inactivation of the protein/enzyme. Depending on the extension of the damage, the functional recuperation of the Fe-S protein requires specialized machineries for repair or de novo assembly of the cluster. Repair of Iron Centres (RIC) are a family of di-iron proteins whose first member was identified in Escherichia coli (formely YtfE) as having an unprecedented role in the protection of Fe-S centres by delivering iron for the formation of Fe-S clusters1,2. We show that in human pathogens such as Staphylococcus aureus, Neisseria gonorrhoeae and Trichomonas vaginalis RIC confers protection against nitrogen and oxygen reactive species. Moreover, we demonstrate that RIC is required for full virulence of S. aureus upon infection of the wax moth larva Galleria mellonella3–5.