Mutations in the ubiquitin gene of Saccharomyces cerevisiae accompanied by divergent use of CUG codon affect morphogenesis in Candida albicans

Abstract

UbEP42, a mutant of ubiquitin constitutes four mutations, namely S20F, A46S, L50P, and I61T. Characterization of UbEP42 and the isolated mutations revealed that UbEP42, UbL50P, and UbI61T conferred dosage-dependent lethality on
S. cerevisiae, while UbS20F and UbA46S produced no effect over survival. In the present study, opportunistic human pathogen Candida albicans has been employed here to investigate the influence of ubiquitin mutations of S. cerevisiae on morphogenesis, besides various ubiquitin-dependent functions. The codon for leucine ‘CUG’ in S. cerevisiae is read as serine in C. albicans. Hence the protein variants expressed from the S. cerevisiae gene are added with the prefix ‘Sc’. ScUbEP42, ScUbL50P, and ScUbI61T had a negative influence over protein trafficking, lysosomal degradation of proteins, and polyubiquitination with K48 and K63 linkages in C. albicans as in S. cerevisiae. ScUbEP42 and all four derivative mutations impaired the morphogenesis of the yeast form into infective hyphal form. The impairment of morphogenesis of
C. albicans by ubiquitin mutations is unprecedented and suggests a target pathway for future therapeutics.