In vivo detection of Staphylococcus aureus endocarditis by targeting pathogen-specific prothrombin activation

Peter Panizzi, Matthias Nahrendorf*, Jose-Luiz Figueiredo, Jennifer Panizzi, Brett Marinelli, Yoshiko Iwamoto, Edmund Keliher, Ashoka A. Maddur, Peter Waterman, Heather K. Kroh, Florian Leuschner, Elena Aikawa, Filip K. Swirski, Mikael J. Pittet, Tilman M. Hackeng, Pablo Fuentes-Prior, Olaf Schneewind, Paul E. Bock, Ralph Weissleder

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

111 Citations (Web of Science)

Abstract

Coagulase-positive Staphylococcus aureus (S. aureus) is the major causal pathogen of acute endocarditis, a rapidly progressing, destructive infection of the heart valves. Bacterial colonization occurs at sites of endothelial damage, where, together with fibrin and platelets, the bacteria initiate the formation of abnormal growths known as vegetations. Here we report that an engineered analog of prothrombin could be used to detect S. aureus in endocarditic vegetations via noninvasive fluorescence or positron emission tomography (PET) imaging. These prothrombin derivatives bound staphylocoagulase and intercalated into growing bacterial vegetations. We also present evidence for bacterial quorum sensing in the regulation of staphylocoagulase expression by S. aureus. Staphylocoagulase expression was limited to the growing edge of mature vegetations, where it was exposed to the host and co-localized with the imaging probe. When endocarditis was induced with an S. aureus strain with genetic deletion of coagulases, survival of mice improved, highlighting the role of staphylocoagulase as a virulence factor.
Original languageEnglish
Pages (from-to)1142-U153
JournalNature Medicine
Volume17
Issue number9
DOIs
Publication statusPublished - Sep 2011

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