Study of Staphylococcus aureus pathogenic genes by transfer and expression in the less virulent organism Streptococcus gordonii.
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.
Stutzmann Meier
P
P
Division of Infectious Diseases, Department of Internal Medicine Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland.
Entenza
J M
JM
Vaudaux
P
P
Francioli
P
P
Glauser
M P
MP
Moreillon
P
P
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
D003030:Coagulase