Candida albicans: adherence, signaling and virulence

The focus of this symposium was to present new information on the morphogen esis of Candida albicans, particularly how it relates to signal transductio n pathways and other genes involved in the regulation of morphogenesis. In addition, we discuss the role of adherence and colonization of the oral cav ity by the organism and discuss the role of mannan as an adhesin that recog nizes the human red blood cell. C. albicans utilizes at least two signal pa thways to regulate its conversion from a yeast form to filamentous growth ( hyphae). One of these two pathways is similar to the Saccharomyces cerevisi ae pseudohyphal/mating pathway, which utilizes the regulatory protein, Cph1 p. The other pathway is not totally defined but requires a second regulator y protein, referred to as Efg1p. Other signal pathways may exist, which inc lude a two-component histidine kinase and response regulator proteins. The latter pathway(s) may include proteins such as Chk1p, Ssk1p, Shi1p and Cos1 p/Nik1p. Mutations in strains, which specifically target these proteins, re sult in morphogenesis defects and avirulence or attenuation of strains. A g rowth regulatory gene has also been recently defined whose expression is as sociated with growth cessation and which appears to be a necessary prerequi site in conversion of the organism to a filamentous growth form. Starvation of yeast cells induces exponentially grown cells (and usually non-germinat ive) to germinate. This phenomenon is also observed in cells that are trans iently treated with metabolic inhibitors. During each of these treatments ( starvation, metabolic inhibition), expression of a growth regulatory gene ( CGRI) increases. Adherence of C, albicans to host cells and tissues is comp lex; several proteins, which appear to have host recognition functions, hav e been defined. In the oral cavity, C. albicans selectively adheres to sali vary proteins, which are absorbed to many oral surfaces. This mechanism ena bles the cells to colonize surfaces of the oral cavity. An understanding of these interactions may lead to strategies to prevent oral disease. Mannan from C. albicans may provide a host recognition function for C. albicans. R ecent experiments indicate that mannan binds to human red blood cells and c auses hemolysis, Binding of mannan to the band 3 protein of human red blood cells has been established. This activity may be associated with the abili ty of the organism to utilize hemoglobin (and iron).