Staphylococcus aureus infections are associated with
abscess formation and bacterial persistence; however, the genes that enable this lifestyle are not known. We show here that following intravenous
infection of mice, S. aureus disseminates rapidly into organ tissues and elicits
abscess lesions that develop over weeks but cannot be cleared by the host. Staphylococci grow as communities at the center of
abscess lesions and are enclosed by pseudocapsules, separating the pathogen from immune cells. By testing insertional variants in genes for cell wall-anchored
surface proteins, we are able to infer the stage at which these molecules function.
Fibrinogen-
binding proteins ClfA and ClfB are required during the early phase of staphylococcal dissemination. The
heme scavenging factors IsdA and IsdB, as well as SdrD and
protein A, are necessary for
abscess formation. Envelope-associated
proteins, Emp and Eap, are either required for
abscess formation or contribute to persistence. Fluorescence microscopy revealed Eap deposition within the pseudocapsule, whereas Emp was localized within staphylococcal
abscess communities.
Antibodies directed against envelope-associated
proteins generated
vaccine protection against staphylococcal
abscess formation. Thus, staphylococci employ envelope
proteins at discrete stages of a developmental program that enables
abscess formation and bacterial persistence in host tissues.