Insight into the human pathodegradome of the V8 protease from Staphylococcus aureus

Staphylococcus aureus possesses ten extracellular proteases with mostly unknown targets in the human proteome. To assist with bacterial protease target discovery, we have applied and compared two N-terminomics methods to investigate cleavage of human serum proteins by S. aureus V8 protease, discovering 85 host-protein targets. Among these are virulence-relevant complement, iron sequestration, clotting cascade, and host protease inhibitor proteins. Protein cleavage sites have been identified, providing insight into the disruption of host protein function by V8. Complement proteins are cleaved within peptidase and sushi domains, and host protease inhibitors are 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.

Automated summary

In this study, two N-terminomics methods were applied to investigate the cleavage of human serum proteins by the S. aureus V8 protease, leading to the discovery of 85 host-protein targets, including complement, iron sequestration, clotting cascade, and host protease inhibitor proteins. The protease V8 disrupts host protein function through cleavage sites, providing insights into its role in S. aureus pathogenesis.