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Infection and Immunity, September 2008, p. 4120-4128, Vol. 76, No. 9
0019-9567/08/$08.00+0     doi:10.1128/IAI.00376-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Contribution of the Collagen Adhesin Acm to Pathogenesis of Enterococcus faecium in Experimental Endocarditis{triangledown}

Sreedhar R. Nallapareddy,1,2,{dagger} Kavindra V. Singh,1,2,{dagger} and Barbara E. Murray1,2,3*

Division of Infectious Diseases, Department of Internal Medicine,1 Center for the Study of Emerging and Re-Emerging Pathogens,2 Department of Microbiology and Molecular Genetics, University of Texas Medical School, Houston, Texas 770303

Received 24 March 2008/ Returned for modification 19 April 2008/ Accepted 20 June 2008

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 {Delta}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.

* Corresponding author. Mailing address: Division of Infectious Diseases, Department of Internal Medicine, University of Texas Medical School at Houston, 6431 Fannin Street, MSB 2.112, Houston, TX 77030. Phone: (713) 500-6745. Fax: (713) 500-6766. E-mail: bem.asst{at}uth.tmc.edu

{triangledown} Published ahead of print on 30 June 2008.

Editor: S. R. Blanke

{dagger} S.R.N. and K.V.S. contributed equally to this work.

Infection and Immunity, September 2008, p. 4120-4128, Vol. 76, No. 9
0019-9567/08/$08.00+0     doi:10.1128/IAI.00376-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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