title: Study of Staphylococcus aureus pathogenic genes by transfer and expression in the less virulent organism Streptococcus gordonii.
abstract: Because Staphylococcus aureus strains contain multiple virulence factors, studying their pathogenic role by single-gene inactivation generated equivocal results. To circumvent this problem, we have expressed specific S. aureus genes in the less virulent organism Streptococcus gordonii and tested the recombinants for a gain of function both in vitro and in vivo. Clumping factor A (ClfA) and coagulase were investigated. Both gene products were expressed functionally and with similar kinetics during growth by streptococci and staphylococci. ClfA-positive S. gordonii was more adherent to platelet-fibrin clots mimicking cardiac vegetations in vitro and more infective in rats with experimental endocarditis (P < 0.05). Moreover, deleting clfA from clfA-positive streptococcal transformants restored both the low in vitro adherence and the low in vivo infectivity of the parent. Coagulase-positive transformants, on the other hand, were neither more adherent nor more infective than the parent. Furthermore, coagulase did not increase the pathogenicity of clfA-positive streptococci when both clfA and coa genes were simultaneously expressed in an artificial minioperon in streptococci. These results definitively attribute a role for ClfA, but not coagulase, in S. aureus endovascular infections. This gain-of-function strategy might help solve the role of individual factors in the complex the S. aureus-host relationship.
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland.
authors.forename: P
authors.initials: P
authors.lastname: Stutzmann Meier
authors.forename: J M
authors.initials: JM
authors.lastname: Entenza
authors.forename: P
authors.initials: P
authors.lastname: Vaudaux
authors.forename: P
authors.initials: P
authors.lastname: Francioli
authors.forename: M P
authors.initials: MP
authors.lastname: Glauser
authors.forename: P
authors.initials: P
authors.lastname: Moreillon
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion; D003030:Coagulase / Q000235:genetics*; D004697:Endocarditis, Bacterial / Q000209:etiology; D051381:Rats; D013211:Staphylococcus aureus / Q000235:genetics / Q000472:pathogenicity*; D013291:Streptococcus / Q000235:genetics / Q000472:pathogenicity*; D014169:Transformation, Bacterial; D014774:Virulence
chemical_list: D003030:Coagulase