Natural mutations in a Staphylococcus aureus virulence regulator attenuate cytotoxicity but permit bacteremia and abscess formation
Das S., Lindemann C., Young BC., Muller J., Österreich B., Ternette N., Winkler A-C., Paprotka K., Reinhardt R., Förstner KU., Allen E., Flaxman A., Yamaguchi Y., Rollier CS., van Diemen P., Blättner S., Remmele CW., Selle M., Dittrich M., Müller T., Vogel J., Ohlsen K., Crook DW., Massey R., Wilson DJ., Rudel T., Wyllie DH., Fraunholz MJ.
Significance Staphylococcus aureus is a major cause of life-threatening bacterial infection. A significant risk factor for infection is nasal carriage. Previously, we reported spontaneous mutations during carriage associated with infection, including loss-of-function of the gene repressor of surface proteins ( rsp ). Here we use genomic screens, experimental assays, and molecular examination of rsp mutants from patients to understand how rsp is involved in infection; we find it has far-reaching effects on gene regulation. Paradoxically, rsp mutants exhibited attenuated toxicity and reduced disease severity early in experimental infection, without sacrificing the ability to cause abscesses and bloodstream infection. This work reveals a complex relationship between correlates of disease in the laboratory and in patients, demonstrating that life-threatening disease can be associated with reduced severity early in infection.