A nickel ABC-transporter of Staphylococcus aureus is involved in urinary tract infection

The oligopeptide transport systems Opp belong to the nickel/peptide/opine PepT subfamily of ABC-transporters. The opportunist pathogen Staphylococcus aureus encodes four putative Opps and one orphean substrate binding protein Opp5A. Here, we report that the Opp2 permease complex (Opp2BCDF) and Opp5A are involved in nickel uptake and then renamed them NikBCDE and NikA respectively. S. aureus carries also a high-affinity nickel transporter NixA belonging to the NiCoT family of secondary transporters. The activity of these two nickel transporters determine that of urease, a multimeric nickel-dependent enzyme mainly involved in the neutralization of acidic environments. However, only the Nik system was responsible for the neutralization and deposit of pH-dependent crystals in human urine. Inactivation of the nik genes affected bacterial colonization of mouse urinary tract, as well as the 50% infective dose levels compared with the parental and nixA strains. Finally, complementation of the nik mutations restored bacterial colonization. Together, our results suggest a role for the Nik system in the urinary tract infection by S. aureus, probably due to the urease-mediated pH increase of the urine