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To cause disease, they must survive in blood and invade the central nervous system by penetrating the blood-brain barrier.<jats:italic>C. sakazakii<\/jats:italic>BAA-894 possesses an \u223c131-kb plasmid (pESA3) that encodes an outer membrane protease (Cpa) that has significant identity to proteins that belong to the Pla subfamily of omptins. Members of this subfamily of proteins degrade a number of serum proteins, including circulating complement, providing protection from the complement-dependent serum killing. Moreover, proteins of the Pla subfamily can cause uncontrolled plasmin activity by converting plasminogen to plasmin and inactivating the plasmin inhibitor \u03b12-antiplasmin (\u03b12-AP). These reactions enhance the spread and invasion of bacteria in the host. In this study, we found that an isogenic<jats:italic>cpa<\/jats:italic>mutant showed reduced resistance to serum in comparison to its parent<jats:italic>C. sakazakii<\/jats:italic>BAA-894 strain. Overexpression of Cpa in<jats:italic>C. sakazakii<\/jats:italic>or<jats:italic>Escherichia coli<\/jats:italic>DH5\u03b1 showed that Cpa proteolytically cleaved complement components C3, C3a, and C4b. Furthermore, a strain of<jats:italic>C. sakazakii<\/jats:italic>overexpressing Cpa caused a rapid activation of plasminogen and inactivation of \u03b12-AP. These results strongly suggest that Cpa may be an important virulence factor involved in serum resistance, as well as in the spread and invasion of<jats:italic>C. sakazakii<\/jats:italic>.<\/jats:p>","DOI":"10.1128\/iai.01165-10","type":"journal-article","created":{"date-parts":[[2011,1,19]],"date-time":"2011-01-19T04:51:07Z","timestamp":1295412667000},"page":"1578-1587","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":74,"title":["Cpa, the Outer Membrane Protease of<i>Cronobacter sakazakii<\/i>, Activates Plasminogen and Mediates Resistance to Serum Bactericidal Activity"],"prefix":"10.1128","volume":"79","author":[{"given":"A. A.","family":"Franco","sequence":"first","affiliation":[{"name":"Center for Food Safety and Applied Nutrition, U.S. Food and Drug Administration, Laurel, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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