adhesion-candida-parapsilosis-to-bovine-serum-albumin-under-fluid

Adhesion of <em>Candida parapsilosis</em> to Bovine Serum Albumin under Fluid Shear

C. parapsilosis (Cp) is an emerging cause of bloodstream infections in certain populations. The&#160;Candida clade, including Cp, is increasingly ...

Women & Infants Hospital of Rhode Island and Warren Alpert Medical School of Brown University

This study evaluates the conditions in which peripheral blood mononuclear cells mediate toxicity to Candida albicans opsonized with heat-inactivated human serum. Serum concentrations as low as 1% resulted in 50% inhibition of C. albicans metabolic activity after incubation with peripheral blood mononuclear cells at an effector to target ratio of 8. Measurable inhibition was also achieved at lower effector to target ratios and lower serum concentrations, and at least a portion of the metabolic inhibition reflected fungal cell death. Depletion of C. albicans-specific antibody decreased the toxic effect while opsonization with purified human IgG restored toxicity, and cell-cell contact between peripheral blood mononuclear cells and fungus was required. Depletion of or enrichment for monocytes from the peripheral blood mononuclear cells preparation diminished the toxic effect and the monocytic cell line, THP-1, was likewise incapable of toxicity. These studies provide evidence that antibody augments antifungal host defense and underscore the complex interrelationship between humoral and cellular immunity in these infections.

Toxicity to Candida albicans mediated by human serum and peripheral blood mononuclear cells.

Very low birth weight infants (VLBW, < or = 1500 g) are at increased risk for invasive disease caused by fungi, and colonization is an important risk factor. This study was designed to examine the effect of maternal flora on Candida colonization of VLBW infants.

Vertical and horizontal transmission of Candida albicans in very low birth weight infants using DNA fingerprinting techniques.

Colonization increases risk for invasive candidiasis in neonates. Breast milk host defense proteins may affect yeast colonization of infants.

Host Defense Proteins in Breast Milk and Neonatal Yeast Colonization.

The yeast  is an increasingly common cause of systemic fungal infections among immunocompromised individuals, including premature infants. Adhesion to host surfaces is an important step in pathogenesis, but this process has not been extensively studied in this organism. A microfluidics assay was developed to test the ability of  to adhere to immobilized host extracellular matrix proteins under physiological fluid shear conditions. Growth in mammalian tissue culture medium at 37°C for 3 to 6 h led to the induction of an adhesive phenotype at shear forces of 1 to 5 dynes/cm in some isolates of  Glutamic acid, proline, and calcium appeared to be the minimally necessary requirements for increased adhesion in these assays. To determine whether genes homologous to the  gene family of  were important for the adhesive phenotype, the expression levels of 5 homologous  genes were quantified by using quantitative PCR (qPCR) under conditions leading to increased adhesion.  () and  showed increased expression levels compared to those in control yeast. The extent of adhesion was variable among different isolates, and linear regression identified the expression of  but not  as having a strong positive correlation with adhesion. A homozygous  deletion strain was deficient in adhesion, whereas the expression of  in  resulted in increased adhesion. Together, these data provide strong evidence that CpAls7 aids in the adherence of  to the extracellular matrix under shear forces and support its previously reported role in virulence.

Role of the Inducible Adhesin CpAls7 in Binding of Candida parapsilosis to the Extracellular Matrix under Fluid Shear.

Invasive candidiasis is an important cause of fungal infections in immunocompromised patients, including premature infants. The S-type lectin, galectin-3 (gal3), is increasingly recognized for its role in antifungal host defense. This study tested the hypothesis that tissue gal3 expression is affected by disseminated infection with Candida albicans and that supplementation with gal3 will provide a benefit in this setting.

Joseph M. Bliss

Women & Infants Hospital of Rhode Island and Warren Alpert Medical School of Brown University

Adhesion of Candida parapsilosis to Bovine Serum Albumin under Fluid Shear