Insight into the Human Pathodegradome of the V8 Protease From  <i>Staphylococcus aureus</i>

Abstract

Staphylococcus aureus possesses ten extracellular proteases, with mostly unknown targets in the human proteome. To assist with bacterial protease target discovery, we appliedand compared two N-terminomics methods to investigate cleavage of human serum proteins by S. aureus V8 protease, discovering 85 host-protein targets. Amongst these were virulence-relevant complement, iron sequestration, clotting cascade, and host protease inhibitor proteins. Protein cleavage sites were identified, providing insight into the disruption of host protein function by V8. Complement proteins were cleaved within peptidase and sushi domains, and host protease inhibitors were cleaved outside their protease-trapping motifs. Our data highlight the potential for further application of N-terminomics in discovery of bacterial protease substrates in other host niches, and provide omics-scale insight into the role of the V8 protease in S. aureus pathogenesis.