GENETIC ANALYSIS OF ENTEROCOCCI

University Of Texas Hlth Sci Ctr Houston, Houston TX

Investigators

Linked publications & trials

Abstract

DESCRIPTION ( Applicant's Abstract): Enterococci are the third most common cause of endocarditis, behind streptococci and staphylococci, and the second or third most common cause of hospital acquired infections; among these, Enterococcus faecalis is the predominant species isolated. Antimicrobial resistance likely enhances the role of enterococci in nosocomial infections and certainly make it more difficult to successfully treat patients, particularly those with endocarditis. The central hypothesis of this work is that by better understanding enterococci, new therapeutic or preventative modalities can be developed. Work during the current funding period has 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 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 appears to regulate an enterococcal gelatinase and a serine protease that also influence virulence in mice. In the renewal application, the investigators propose (1) to verify that the agr-like locus regulates gelE and sprE and if all are important for virulence; to determine the commonality of these genes among E. faecalis, and to determine how the enterococcal agr-like locus is regulated and if it, like 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 they 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, including over 17 from patients with E. faecalis endocarditis) 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. In their "Methodologic" Specific Aims, they plan (4) to devise a system for constructing non-polar deletion mutants using counter-selection, based on their prior work with E. faecalis pyr mutants, and to develop additional assays to look at bacterial persistence and less acute infections that would help us avoid lethality models. They hope that results from this work will provide solid leads in their quest for methods to prevent, control, or combat E. faecalis infections.