Enterococci are the 3 most common cause of endocarditis, behind streptococci and staphylococci, and the 2-3 most common cause of hospital acquired infections, with Enterococcusfaecalis being the predominant species isolated. Antimicrobial resistance likely facilitatesthe establishment of enterococci in nosocomial infec- tions and certainly makes it more difficult to successfullytreat patients, particularly those with endocarditis. The central hypothesis of this project is that by better understanding enterococci, new therapeutic or preventative mo- dalities can be developed. Work during a previously funded grant identified and characterized a number of anti- gen encoding genes;a polysaccharide gene cluster (epa) that appears to influencevirulence in mice;different ad- herence 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 or staphylococci that is involved in expression of an E. faecalis gelati- nase and a senne protease that also influence virulence in mice. In this application, we propose m to verify that the E.faecalis a^r-like locus regulates gelE and sprE and determine if all are important for virulence;to investi- gate the distribution of these genes among E. faecalis;and to determine how the enterococcal aer-like locus is regulated and if it, like the staphylococcal agr, regulates other genes. We also plan (2) to test the hypothesis that Ace (a newly described adhesm for collagen of enterococci) is the cause of the adherence we haye 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 recombinantAce and patient sera) in- fected by E.faecalis and if antibody made during infection, or antibody to recombinant Ace, is protective. In our third specific aim, we 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. We will also explore a system for constructing non-polar dele^n mutants usingcoun- terselection, based on our prior work with the E.faecalis pyr genes, and to explore additionalassays thatwould help us avoid lethalitymodels. We hope that results from this work will provide solid leads in our quest for meth- ods to prevent, control, or combat E.faecalis infections.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37AI047923-10
Application #
7585264
Study Section
Special Emphasis Panel (NSS)
Program Officer
Huntley, Clayton C
Project Start
2000-08-01
Project End
2010-02-28
Budget Start
2009-03-01
Budget End
2010-02-28
Support Year
10
Fiscal Year
2009
Total Cost
$414,389
Indirect Cost
Name
University of Texas Health Science Center Houston
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
800771594
City
Houston
State
TX
Country
United States
Zip Code
77225
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
Cohen, Ana Luisa V; Roh, Jung Hyeob; Nallapareddy, Sreedhar R et al. (2013) Expression of the collagen adhesin ace by Enterococcus faecalis strain OG1RF is not repressed by Ers but requires the Ers box. FEMS Microbiol Lett 344:18-24
Arias, Cesar A; Murray, Barbara E (2012) The rise of the Enterococcus: beyond vancomycin resistance. Nat Rev Microbiol 10:266-78
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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