Identification and characterization of a Candida albicans alpha-1,2 mannosyltransferase CaMNN5 that suppresses the iron-dependent growth defect of Saccharomyces cerevisiae aft1 delta mutant

Abstract

In S. cerevisiae the transcription factor Aft1p plays a central role in regulating many genes involved in iron acquisition and utilization. Through a genetic screening for C. albicans genes that allow the aft1i?? mutant to grow under iron-limiting conditions, I have isolated a C. albicans I?-1,2-mannosyltransferease CaMnn5p, which specifically enhances an endocytosis-dependent of iron uptake in S. cerevisiae. Characterization in C. albicans showed that the I?-1,2-mannosyltransferease activity of CaMnn5p requires Mn2+ as co-factor and is regulated by Fe2+ concentration, suggesting an underlying relationship between CaMnn5p activity and cellular iron homeostasis. Camnn5 deletion mutant showed lowered ability in extending both N- and O-linked mannans, hypersensitivity to cell wall-damaging agents and reduction of cell wall mannophosphate content, phenotypes typical of many fungal mannosyltransferase mutants. Camnn5i?? also exhibits some unique defects, such as impaired hyphal growth on solid media and attenuated virulence in mice. Thus, CaMnn5p may be a potential target for anti-Candida drug development.