Contribution of the Collagen Adhesin Acm to Pathogenesis of Enterococcus faecium in Experimental Endocarditis
- 1 September 2008
- journal article
- Published by American Society for Microbiology in Infection and Immunity
- Vol. 76 (9), 4120-4128
- https://doi.org/10.1128/iai.00376-08
Abstract
Enterococcus faecium is a multidrug-resistant opportunist causing difficult-to-treat nosocomial infections, including endocarditis, but there are no reports experimentally demonstrating E. faecium virulence determinants. Our previous studies showed that some clinical E. faecium isolates produce a cell wall-anchored collagen adhesin, Acm, and that an isogenic acm deletion mutant of the endocarditis-derived strain TX0082 lost collagen adherence. In this study, we show with a rat endocarditis model that TX0082 Δ acm :: cat is highly attenuated versus wild-type TX0082, both in established (72 h) vegetations ( P < 0.0001) and for valve colonization 1 and 3 hours after infection ( P ≤ 0.0002), making Acm the first factor shown to be important for E. faecium pathogenesis. In contrast, no mortality differences were observed in a mouse peritonitis model. While 5 of 17 endocarditis isolates were Acm nonproducers and failed to adhere to collagen in vitro, all had an intact, highly conserved acm locus. Highly reduced acm mRNA levels (≥50-fold reduction relative to an Acm producer) were found in three of these five nonadherent isolates, including the sequenced strain TX0016, by quantitative reverse transcription-PCR, indicating that acm transcription is downregulated in vitro in these isolates. However, examination of TX0016 cells obtained directly from infected rat vegetations by flow cytometry showed that Acm was present on 40% of cells grown during infection. Finally, we demonstrated a significant reduction in E. faecium collagen adherence by affinity-purified anti-Acm antibodies from E. faecium endocarditis patient sera, suggesting that Acm may be a potential immunotarget for strategies to control this emerging pathogen.Keywords
This publication has 29 references indexed in Scilit:
- A Functional Collagen Adhesin Gene, acm , in Clinical Isolates of Enterococcus faecium Correlates with the Recent Success of This Emerging Nosocomial PathogenInfection and Immunity, 2008
- Inhibition of Enterococcus faecium Adherence to Collagen by Antibodies against High-Affinity Binding Subdomains of AcmInfection and Immunity, 2007
- Importance of theebp(Endocarditis‐ and Biofilm‐Associated Pilus) Locus in the Pathogenesis ofEnterococcus faecalisAscending Urinary Tract InfectionThe Journal of Infectious Diseases, 2007
- Endocarditis and biofilm-associated pili of Enterococcus faecalisJCI Insight, 2006
- Ligand-Signaled Upregulation of Enterococcus faecalis ace Transcription, a Mechanism for Modulating Host- E. faecalis InteractionInfection and Immunity, 2006
- Decreased Virulence of a gls24 Mutant of Enterococcus faecalis OG1RF in an Experimental Endocarditis ModelInfection and Immunity, 2005
- Anti-Clumping Factor A Immunoglobulin Reduces the Duration of Methicillin-ResistantStaphylococcus aureusBacteremia in an Experimental Model of Infective EndocarditisAntimicrobial Agents and Chemotherapy, 2003
- Activation and Transcriptional Interaction betweenagrRNAII and RNAIII inStaphylococcus aureusIn Vitro and in an Experimental Endocarditis ModelThe Journal of Infectious Diseases, 2002
- Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT MethodMethods, 2001
- The Collagen-Binding Adhesin Is a Virulence Factor in Staphylococcus aureus KeratitisInfection and Immunity, 2000