Molecular Analysis of the Enterococcus faecalis Serotype 2 Polysaccharide Determinant

Autor: Lynn E. Hancock, Brett D. Shepard, Michael S. Gilmore
Rok vydání: 2003
Předmět:
Zdroj: Journal of Bacteriology. 185:4393-4401
ISSN: 1098-5530
0021-9193
Popis: Enterococcus faecalis has emerged as a leading cause of nosocomial bacteremia, surgical site infection, and urinary tract infection (29). The development of multiple antibiotic resistances in enterococci in recent years compromises existing therapies, highlighting the need for a better understanding of the pathogenicity of the organism and the development of new treatment strategies (13). Only a few traits are known to contribute to the pathogenesis of enterococcal infection (23). In recent years, several papers have examined the role that bacterial polysaccharides play in the biology of enterococcal infection (2, 3, 12, 15, 16, 37, 40). Bottone et al. (3) described several E. faecalis clinical isolates isolated from urinary tract infections which were highly encapsulated. Huebner et al. (16) reported detection of a capsule consisting of a glucose-glycerol phosphate polymer present in a portion of E. faecalis (33%) and Enterococcus faecium (28%) isolates, which protected these organisms from phagocytic killing in the absence of opsonic antibodies. More recently, Huebner et al. (15) showed the efficacy of the purified capsule as a serotype vaccine candidate. Mice passively immunized with anticapsular antibody demonstrated enhanced clearance of the organism. Xu et al. (39, 40) described a polysaccharide operon in E. faecalis strain OG1RF, which when expressed in Escherichia coli conferred reactivity with sera from patients with enterococcal endocarditis. The limitation of these findings was that the same antisera could not detect a polysaccharide antigen on the surface of the same E. faecalis strain. More recently, Teng et al. (37) identified a cell wall polysaccharide from E. faecalis strain OG1RF reactive with patient serum, but only after liberating the polymer from the cell wall by lysozyme digestion. This is in contrast to the capsular polysaccharide from E. faecalis, which is readily agglutinated by using intact cells and serotype-specific antibodies (12). We previously reported an operon in E. faecalis that codes for the biosynthesis of the serotype 2 capsular polysaccharide (12). Insertional inactivation of genes within this pathway resulted in a loss of reactivity with type 2 antisera. Moreover, these mutants had significantly reduced ability to persist at sites of infection. It was further shown that human polymorphonuclear leukocytes more readily phagocytosed a mutant defective in expression of the serotype polysaccharide, a hallmark of bacterial encapsulation. This capsule determinant was found to be conserved in a number of clinical isolates, including the vancomycin-resistant strain V583 (31), from which the genome sequence is being derived (L. Bannerjei, personal communication). Because of its role in the pathogenesis of enterococcal infection and its potential value in deriving alternative therapeutic approaches for an agent increasingly refractory to antibiotics, it was of interest to analyze the underlying genetics of E. faecalis serotype 2 capsular polysaccharide expression.
Databáze: OpenAIRE