Phenotype switching affects biofilm formation by Candida parapsilosis

Abstract

Generation of biofilms by the pathogenic yeast Candida parapsilosis is correlated closely with disease. The phenomenon of phenotype switching in 20 isolates of C. parapsilosis was examined and the relationship with biofilm development was investigated. Four stable and heritable phenotypes were identified -crepe, concentric, smooth and crater. Cells from crepe and concentric phenotypes are almost entirely pseudohyphal, whilst cells from smooth and crater phenotypes are mostly yeast-like. The pseudohyphae from concentric phenotypes are approximately 45 % wider than those from crepe cells. The cell size of the smooth phenotype is smaller than those of the other three phenotypes. On polystyrene surfaces, the concentric phenotype generates up to twofold more biofilm than the crepe and crater phenotypes. Smooth phenotypes generate the least biofilm. Concentric phenotypes also invade agar surfaces more than the crepe and crater phenotypes, whilst smooth phenotypes do not invade at all. The smooth phenotype, however, grows significantly faster than the others. The quorum-sensing molecule farnesol inhibits formation of biofilms by the crepe, concentric and crater phenotypes. INTRODUCTIONThe yeast Candida parapsilosis is found frequently as a commensal organism on epithelial and mucosal tissues, but it is also an increasing cause of hospital-acquired infection (Weems, 1992). Although C. parapsilosis is responsible for approximately 16 % of general Candida infections, it is a particular problem in critically ill neonates (Hajjeh et al., 2004;Pfaller & Diekema, 2004;Roilides et al., 2004). Fungaemia caused by C. parapsilosis is associated with the presence of catheters and the use of parenteral nutrition (Shin et al., 2002). This is probably due to the ability of the yeast to grow as biofilms, especially in highglucose environments (Branchini et al., 1994). Biofilms are inherently resistant to treatment with antifungal drugs and the infected device must usually be removed.Formation of biofilms by organisms growing in association with a surface is a very common phenomenon among yeast and bacterial species (Hall-Stoodley et al., 2004;Jabra-Rizk et al., 2004). In yeast, the most detailed descriptions of biofilm structure come from studies on Candida albicans (Baillie & Douglas, 1999; Chandra et al., 2001;Hawser & Douglas, 1994;Kumamoto, 2002;Shin et al., 2002). In general, a layer of cells in the yeast form is found attached to the surface, with a layer of filamentous cells above, surrounded by an exopolymeric matrix (Kumamoto, 2002). Cells in biofilms are associated with a specific geneexpression pattern, including the overexpression of amino acid biosynthetic genes, particularly those for amino acids containing sulfur (García-Sánchez et al., 2004). Biofilm growth requires activation of the filamentation pathway and mutants defective in regulators of filamentation, such as efg1 and cph1, are unable to form biofilms (Ramage et al., 2002b). C. parapsilosis is not capable of forming true filaments and biofilms are often composed...

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