Importance of the Collagen Adhesin Ace in Pathogenesis and Protection against Enterococcus faecalis Experimental Endocarditis

PLoS Pathogens

Jouko Sillanpää¹  Sreedhar R. Nallapareddy²  Kavindra V. Singh³  Barbara E. Murray³ 

[1] University of Texas Medical School, Houston, Texas, United States of America;Center for the Study of Emerging and Re-emerging Pathogens;Division of Infectious Diseases, Department of Internal Medicine, University of Texas Medical School, Houston, Texas, United States of America

关键词: Enterococcus faecalis;    Endocarditis;    Collagens;    Deletion mutagenesis;    Antibodies;    Enterococcus infections;    Complement system;    Flow cytometry;   

DOI  :  10.1371/journal.ppat.1000716

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Ace is an adhesin to collagen from Enterococcus faecalis expressed conditionally after growth in serum or in the presence of collagen. Here, we generated an ace deletion mutant and showed that it was significantly attenuated versus wild-type OG1RF in a mixed infection rat endocarditis model (P<0.0001), while no differences were observed in a peritonitis model. Complemented OG1RFΔace (pAT392::ace) enhanced early (4 h) heart valve colonization versus OG1RFΔace (pAT392) (P = 0.0418), suggesting that Ace expression is important for early attachment. By flow cytometry using specific anti-recombinant Ace (rAce) immunoglobulins (Igs), we showed in vivo expression of Ace by OG1RF cells obtained directly from infected vegetations, consistent with our previous finding of anti-Ace antibodies in E. faecalis endocarditis patient sera. Finally, rats actively immunized against rAce were less susceptible to infection by OG1RF than non-immunized (P = 0.0004) or sham-immunized (P = 0.0475) by CFU counts. Similarly, animals given specific anti-rAce Igs were less likely to develop E. faecalis endocarditis (P = 0.0001) and showed fewer CFU in vegetations (P = 0.0146). In conclusion, we have shown for the first time that Ace is involved in pathogenesis of, and is useful for protection against, E. faecalis experimental endocarditis.

【 授权许可】

CC BY