Enterococci are the 3rd most common cause of endocarditis, behind streptococci and staphylococci, and the 2nd or 3rd most common cause of hospital acquired infections, with Enterococcus faecalis being the predominant species isolated. Antimicrobial resistance likely facilitates the establishment of enterococci in nosocomial infections and certainly makes it more difficult to successfully treat patients, particularly those with endocarditis. The central hypothesis of this project is that by better understanding enterococci, new therapeutic or preventative modalities can be developed. Work during a previously funded grant identified and characterized a number of antigen encoding genes; a polysaccharide gene cluster (epa) that appears to influence virulence in mice; different adherence phenotypes, and a gene, ace, that appears to be involved in adherence; and a gene locus with homology to the accessory gene regulator (agr) locus of staphylococci that is involved in expression of an E. faecalis gelatinase and a serine protease that also influence virulence in mice. In this application, the investigators propose (1) to verify that the E. faecalis agr-like locus regulates gelE and sprE and determine if all are important for virulence; to investigate the distribution of these genes among E. faecalis; and to determine how the enterococcal agr-like locus is regulated and if it, like the staphylococcal agr, regulates other genes. They also plan (2) to test the hypothesis that Ace (a newly described adhesin for collagen of enterococci) is the cause of the adherence we have reported and is important for virulence; to explore the regulation of Ace production; and to determine the distribution and effect of variations in ace, if Ace elicits an antibody response in humans (using recombinant Ace and patient sera) infected by E. faecalis and if antibody made during infection, or antibody to recombinant Ace, is protective. In their third specific aim, they plan (3) to establish if the polysaccharide gene cluster is the cause of a recently described mucoid phenotype, to study its regulation, and to further test its contribution to adherence to foreign material, virulence and protection. They will also explore a system for constructing non-polar deletion mutants using counter-selection based on their prior work with the E. faecalis pyr genes, and to explore additional assays that would help to avoid lethality models. The investigators hope that results from this work will provide solid leads in the quest for methods to prevent, control, or combat E. faecalis infections.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Method to Extend Research in Time (MERIT) Award (R37)
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Bacteriology and Mycology Subcommittee 2 (BM)
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University of Texas Health Science Center Houston
Internal Medicine/Medicine
Schools of Medicine
United States
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Roh, Jung Hyeob; Singh, Kavindra V; La Rosa, Sabina Leanti et al. (2015) The two-component system GrvRS (EtaRS) regulates ace expression in Enterococcus faecalis OG1RF. Infect Immun 83:389-95
Chowdhury, Shahreen A; Nallapareddy, Sreedhar R; Arias, Cesar A et al. (2014) The majority of a collection of U.S. endocarditis Enterococcus faecalis isolates obtained from 1974 to 2004 lack capsular genes and belong to diverse, non-hospital-associated lineages. J Clin Microbiol 52:549-56
Kang, Mingsong; Ko, Ya-Ping; Liang, Xiaowen et al. (2013) Collagen-binding microbial surface components recognizing adhesive matrix molecule (MSCRAMM) of Gram-positive bacteria inhibit complement activation via the classical pathway. J Biol Chem 288:20520-31
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Nallapareddy, Sreedhar R; Sillanpaa, Jouko; Mitchell, Jennifer et al. (2011) Conservation of Ebp-type pilus genes among Enterococci and demonstration of their role in adherence of Enterococcus faecalis to human platelets. Infect Immun 79:2911-20
Arias, Cesar A; Panesso, Diana; McGrath, Danielle M et al. (2011) Genetic basis for in vivo daptomycin resistance in enterococci. N Engl J Med 365:892-900
Pinkston, Kenneth L; Gao, Peng; Diaz-Garcia, Daniel et al. (2011) The Fsr quorum-sensing system of Enterococcus faecalis modulates surface display of the collagen-binding MSCRAMM Ace through regulation of gelE. J Bacteriol 193:4317-25
Galloway-Pena, Jessica R; Bourgogne, Agathe; Qin, Xiang et al. (2011) Diversity of the fsr-gelE region of the Enterococcus faecalis genome but conservation in strains with partial deletions of the fsr operon. Appl Environ Microbiol 77:442-51
Nallapareddy, Sreedhar R; Singh, Kavindra V; Sillanpaa, Jouko et al. (2011) Relative contributions of Ebp Pili and the collagen adhesin ace to host extracellular matrix protein adherence and experimental urinary tract infection by Enterococcus faecalis OG1RF. Infect Immun 79:2901-10

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