3 years ago

The intracellular cyclophilin PpiB contributes to the virulence of Staphylococcus aureus independent of its PPIase activity.

Ronan K Carroll, Marcus A Wittekind, Richard E Wiemels, Rachel L Zapf, Rebecca A Keogh
The Staphylococcus aureus cyclophilin PpiB is an intracellular peptidyl prolyl cistrans isomerase (PPIase) that has previously been shown to contribute to secreted nuclease and hemolytic activity. In this study, we investigate the contribution of PpiB to S. aureus virulence. Using a murine abscess model of infection, we demonstrate that a ppiB mutant is attenuated for virulence. We go on to investigate the mechanism through which PpiB protein contributes to virulence, in particular the contribution of PpiB PPIase activity. We determine the amino acid residues that are important for PpiB PPIase activity and show that a single amino acid substitution (F64A) completely abrogates PPIase activity. Using purified PpiB F64A protein in vitro, we show that PPIase activity only partially contributes to Nuc refolding and that PpiB also possesses a PPIase-independent activity. Using allelic exchange, we introduce the F64A substitution onto the S. aureus chromosome, generating a strain that produces enzymatically inactive PpiB. Analysis of the PpiB F64A strain reveals that PPIase activity is not required for hemolysis of human blood or virulence in a mouse. Together, these results demonstrate that PpiB contributes to S. aureus virulence via a mechanism unrelated to prolyl-isomerase activity.

Publisher URL: http://doi.org/10.1128/IAI.00379-18

DOI: 10.1128/IAI.00379-18

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