Current trends in Candida albicans research

Abstract

Candida albicans is an opportunistic pathogen of human beings and other mammals. Two other features, besides its pathogenicity, have made it a popular organism of study. It exists in different cellular forms and can change from one form to another, depending on growth conditions. Thus, it is being used as a model system to study cellular differentiation. It can also heritably and reversibly switch its cellular and colony morphologies. The yeast is diploid and lacks a sexual cycle. Thus, it has not been possible to apply the powerful methods of genetic analysis to understand morphogenesis or pathogenesis. Few clinical isolates are haploid, but they do not form hyphae and are not yet well characterized. Recombinant DNA techniques are increasingly being applied to C. albicans to solve many of the unanswered questions of morphogenesis and pathogenesis. Genetic transformation and gene-disruption techniques were recently developed for the yeast. Thus it is possible to study the role of any cloned gene through directed mutagenesis. However, the difficulty is to clone the putative genes involved in morphogenesis or pathogenesis. Candida albicans exists in four different cellular forms, namely blastospores, pseudohyphae, hyphae and chlamydospores. Blastospore-to-hypha conversion is well studied. A variety of conditions can induce this transition. It is not clear how cells sense such varied conditions and respond appropriately. In other systems where differentiation is well understood, regulatory genes which control differentiation have been uncovered. These genes cause differential expression of other genes, and ultimately differentiated phenotypes. Thus, it is likely that differential gene expression is involved in the bud-to-hypha transition in C. albicans. Certain proteins are expressed exclusively on the cell surface of hyphae. It should be possible to clone genes coding for these proteins. A study of the expression of these genes might allow us to identify the regulatory gene which determines differentiation. Another approach to understanding morphogenesis is to study how the difference in the shape of buds and hyphae is generated. This difference appears to be due to the differential activity of apical and general growth zones, which determine growth of the cell wall. Activity of these growth zones is apparently determined by actin localization. It remains a possibility that conditions which induce hyphae formation may directly affect actin localization or cell-wall growth zones and cause differences in cell shape. Candida albicans can also heritably switch its cellular phenotype. This has come to light from a study of colony-morphology switching. Some strains can switch their colony morphology, both heritably and reversibly.(ABSTRACT TRUNCATED AT 400 WORDS)