Abstract
ABSTRACT Candida albicans-related bloodstream infections are often associated with infected central venous catheters (CVC) triggered by microbial adhesion and biofilm formation. We utilized single-cell force spectroscopy (SCFS) and flow chamber models to investigate the adhesion behavior of C. albicans yeast cells and germinated cells to naïve and human blood plasma (HBP)-coated CVC tubing. Germinated cells demonstrated up to 56.8-fold increased adhesion forces to CVC surfaces when compared to yeast cells. Coating of CVCs with HBP significantly increased the adhesion of 60-min germinated cells but not of yeast cells and 30-min germinated cells. Under flow conditions comparable to those in major human veins, germinated cells displayed a flow directional-orientated adhesion pattern to HBP-coated CVC material, suggesting the germ tip to serve as the major adhesive region. None of the above-reported phenotypes were observed with germinated cells of an als3Δ deletion mutant, which displayed similar adhesion forces to CVC surfaces as the isogenic yeast cells. Germinated cells of the als3Δ mutant also lacked a clear flow directional-orientated adhesion pattern on HBP-coated CVC material, indicating a central role for Als3 in the adhesion of germinated C. albicans cells to blood exposed CVC surfaces. In the common model of C. albicans, biofilm formation is thought to be mediated primarily by yeast cells, followed by surface-triggered the formation of hyphae. We suggest an extension of this model in which C. albicans germ tubes promote the initial adhesion to blood-exposed implanted medical devices via the germ tube-associated adhesion protein Als3.
Highlights
Candida albicans is a common colonizer of mucosal surfaces of humans, and is present in 75% of the popu lation [1,2]
Since central venous catheters (CVC) surface regions are rapidly covered with blood factors following insertion into a central vein [38,39], we aimed to test the impact of an HBPcoating of the CVC surface on the adhesion forces of C. albicans yeast cells and germinated cells
When rupture lengths were compared (Figure 5b), no clear differences between yeast cells and 30min germinated cells were observed, in line with our findings made with wild type (WT) DSM1386 cells (Figure 3d). These findings suggest that agglutinine-like sequence glycoprotein 3 (Als3) is a major factor contributing to the enhanced adhesion behavior of germinated cells to PU-based CVC tubing, which is in line with earlier findings demonstrating an impor tant role for Als3 in the adhesion process of germi nated C. albicans cells to different epithelial and endothelial cell types [50]
Summary
Candida albicans is a common colonizer of mucosal surfaces of humans, and is present in 75% of the popu lation [1,2]. While colonization by this fungus usually remains benign in healthy individuals, immunosup pressed patients are at increased risk of developing a variety of infections. Oral candidiasis often affects the oropharynx and esophagus of patients infected by HIV. Other risk factors for oral candidiasis include advanced age or the wearing of dentures [3]. As a common infection of the female genital tract, vulvo vaginal candidiasis affects both immunosuppressed and healthy women [4]. In contrast to superficial infections, systemic candidiasis and Candida-associated blood stream infections are life-threatening conditions with mortality rates of up to 35%, even if adequate antifun gal treatment is initiated [5,6,7]
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