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Insight into the Human Pathodegradome of the V8 Protease From  Staphylococcus aureus

40 Pages Posted: 28 Aug 2019 Sneak Peek Status: Review Complete

See all articles by Andrew Frey

Andrew Frey

University of South Florida - Department of Cell Biology, Microbiology and Molecular Biology

Dale Chaput

University of South Florida - Department of Cell Biology, Microbiology and Molecular Biology

Lindsey N. Shaw

University of South Florida - Department of Cell Biology, Microbiology and Molecular Biology

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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.

Keywords: Staphylococcus aureus, degradomics, proteomics, N-terminomics, microbiology, host pathogen interactions, inflammation, protease

Suggested Citation

Frey, Andrew and Chaput, Dale and Shaw, Lindsey N., Insight into the Human Pathodegradome of the V8 Protease From  Staphylococcus aureus (August 27, 2019). Available at SSRN: https://ssrn.com/abstract=3443856 or http://dx.doi.org/10.2139/ssrn.3443856
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Andrew Frey

University of South Florida - Department of Cell Biology, Microbiology and Molecular Biology

United States

Dale Chaput

University of South Florida - Department of Cell Biology, Microbiology and Molecular Biology

United States

Lindsey N. Shaw (Contact Author)

University of South Florida - Department of Cell Biology, Microbiology and Molecular Biology ( email )

United States

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