Cooper, D
Cooper, D. in the species are part of the commensal flora of the mucosa and skin cFMS-IN-2 in humans and other vertebrates. In immunocompromised or intensive-care patients, increased mucosal proliferation secondary to use of broad-spectrum antibiotics, together with reduced host defenses and physical alteration of the cFMS-IN-2 mucosal barriers, may result in bloodstream invasion. Altogether, candidemia accounts for 10% of nosocomial bloodstream infections, and is the causative agent in 50 to 70% of disseminated candidiasis (13, 18, 20, 36, 48). Molecular typing methods have shown an overall genetic similarity between strains obtained from blood cultures and colonizing strains obtained from the gastrointestinal tracts of the same patients, confirming endogenous acquisition as the main source of invasive candidiasis (40, 47). On the basis of this model, adhesion of the yeasts to the epithelium of the digestive tract is a prerequisite for colonization and a critical step in the pathogenesis of invasive candidiasis. Characterization of the adhesins and ligands involved in the with host cell surfaces is mediated by the yeast cell wall, a complex and dynamic structure containing glucan, chitin and mannoproteins (reviewed in reference 6). The outermost layers of the cell wall are made of phosphopeptidomannan (PPM), a polymer of mannose residues and proteins commonly referred to as mannan (3, 6). Mannan has been shown to play a role in adherence (27), immunomodulation (11), and antigenic variability (43). The PPM glycan moiety is composed of O-linked and N-linked oligomannosides. The N-linked part consists of a backbone of -1,6-linked mannopyranose residues with branches composed of -1,2- and -1,3-linked mannopyranose units and terminal -1,2 linkages in cFMS-IN-2 serotype A (7). Short branches composed of -1,2-linked mannopyranose residues are linked to PPM through phosphodiester bridges in serotypes A and B. These side chains are referred to as the acid-labile fraction of PPM, since they are cleaved by mild acid treatment (45). -1,2 oligomannosidic chains have also been identified on a 14- to 18-kDa glycolipid, referred to as phospholipomannan (PLM) (46), that is expressed at and shed from the cell wall (25, 39). -1,2 mannosidic linkages are uncommon structures whose presence has been reported in only few bacterial and yeast species (30, 35). In to the macrophage membrane, at least in part through binding to galectin 3, a member of a family of carbohydrate binding proteins implicated in a variety of biological functions (17, 25). -1,2 oligomannosides also generate protective antibodies (22) and induce cytokine production (26). These unique carbohydrate sequences thus appear to play a key role in the blastospores to Caco-2 cells. Indeed, galectin-3, which binds -1,2 oligomannosides on the macrophage (17), is also expressed in intestinal epithelial cells (1, 8). Moreover, recent studies with a mouse model of candidiasis showed that oral administration of synthetic -1,2 oligomannosides could reduce colonization of the gut, presumably by competing with the natural flora for binding to enterocytes (12). We were thus interested in understanding the basis of this phenomenon at the cellular and molecular levels. Rabbit polyclonal to HDAC5.HDAC9 a transcriptional regulator of the histone deacetylase family, subfamily 2.Deacetylates lysine residues on the N-terminal part of the core histones H2A, H2B, H3 AND H4. MATERIALS AND METHODS Growth and preparation of strain for adherence assay. strain VW32 (serotype A) (5) was used throughout this study. This strain, which was originally isolated from a patient with human renal candidiasis, has been employed in prior.