Drug resistance in the opportunistic pathogens Candida albicans and Candida glabrata

Abstract

There are three major classes of antifungal drug used to treat patients suffering from topical and systemic infections caused by Candida albicans. Both the polyene macrolide antibiotics and the synthetic imidazole derivatives interact with membranes of sensitive organisms causing an impairment of function and cessation of growth. It is possible to obtain mutants of C. albicans resistant to these drugs but they are not a clinical problem. This may result from the fact that the organism is diploid with no haploid stage in its life cycle and the interaction of these compounds with their target is complex involving a number of membrane constituents. In contrast the occurrence of strains of C. albicans resistant to 5-fluorocytosine is a serious clinical problem. Here partial resistance is associated with heterozygosity at the locus coding for UMP pyrophosphorylase. Mitotic segregation can give rise to homozygous resistance in strains where the enzyme is completely absent. This is analogous to acyclovir resistance in herpes simplex virus where resistance is associated with loss of the virus encoded thymidine kinase.