Immunization with FimA protects against Streptococcus parasanguis endocarditis in rats

Abstract

FimA, a surface-associated protein of Streptococcus parasanguis, is associated with initial colonization of damaged heart tissue in an endocarditis model (D. Burnette-Curley, V. Wells, H. Viscount, C. Munro, J. Fenno, P. Fives-Taylor, and F. Macrina, Infect. Immun. 63:4669-4674, 1995). We have evaluated the efficacy of recombinant FimA as a vaccine in the rat model of endocarditis and investigated in vitro the mechanism for the protective role of immunization. FimA-immunized and nonimmunized control animals were catheterized to induce heart valve damage and infected intravenously with 10 7 CFU of wild-type S. parasanguis FW213 bacteria. The presence of bacteria associated with platelet-fibrin vegetations 24 h postchallenge was evaluated. Immunized rats were significantly less susceptible to endocarditis (2 cases among 34 animals) than the control group (21 cases among 33 animals) (P < 0.001). Incubation of S. parasanguis FW213 with rabbit anti-FimA immune serum decreased the mean percent adherence (0.34% of added cells) to platelet-fibrin matrix in vitro compared with that of preimmune normal serum (5.04% of added cells; P < 0.001). Adsorption of immune serum with FimA-positive S. parasanguis FW213 yielded antiserum that failed to block adherence to the platelet-fibrin matrix. We assessed the vaccine potential of FimA as a common immunogen able to provide cross-protection in streptococcal endocarditis by determining the occurrence and expression of fimA in the viridans group streptococci and enterococci. We detected the presence of fimA homologs by Southern hybridization and PCR amplification analyses and determined by immunoblotting the expression of FimA-like proteins among a variety of streptococci and enterococci that frequently cause endocarditis. Eighty-one percent (26 of 32) of streptococcal and enterococcal strains isolated from bacteremic patients expressed proteins that comigrated with FimA and were reactive with polyclonal anti-FimA serum. Streptococcal DNA from strains that were positive by Western blot (immunoblot) analysis hybridized to the full-length fimA probe. Our studies suggest that FimA immunization results in antibody-mediated inhibition of bacterial adherence, a critical early event in the pathogenesis of endocarditis. Our data demonstrate that a majority of streptococcal strains associated with endocarditis have genes that encode FimA-like proteins. Taken together, these results suggest that FimA is a promising candidate for an endocarditis vaccine.

Horizontal gene transfer and host specificity of beta‐haemolytic streptococci: the role of a putative composite transposon containing scpB and lmb

“…Lmb of S. agalactiae displays similarities to LraI proteins of other streptococci and mediates the binding to human laminin (Spellerberg et al, 1999). Besides their role in adhesion (Jenkinson, 1994;Berry and Paton, 1996;Viscount et al, 1997) LraI proteins have been shown to be involved in the transport of divalent cations (Dintilhac et al, 1997;Kolenbrander et al, 1998). However, a typical ABC transporter has not been found in the nucleotide sequence adjacent to the lmb locus, and the addition of manganese did not affect the growth of Lmb mutants (Spellerberg et al, 1999).…”

Identification and characterization of a Streptococcus pyogenes ABC transporter with multiple specificity for metal cations

“…S. pneumoniae and S. parasanguis lraI mutants are attenuated in virulence when examined in animal models (Burnette-Curley et al, 1995;Berry and Paton, 1996). In addition, immunization with the lipoprotein confers protective immunity in mice and rats (Talkington et al, 1996;Viscount et al, 1997).…”

In vivo testing of an Enterococcus faecalis efaA mutant and use of efaA homologs for species identification

“…The translated protein sequence of EfaA was found to show homology to members of a protein family, designated LraI [2], that has now been identi¢ed in a number of streptococcal species [3^5]. Members of this family include ScaA of Streptococcus gordonii, an adhesion-associated protein recently shown to be involved in Mn P transport [6] and that is also a prominent surface antigen [7]; FimA of S. parasanguis, a factor important for endocarditis and a potential vaccine candidate [5]; and PsaA, a virulence-associated determinant of S. pneumoniae. The genes for these proteins are part of tricistronic operons encoding ATP-binding cassette (ABC) transporter systems, in which the aforementioned proteins appear to be the substrate binding components.…”