Influence of Ubiquitin Mutations over Molecular Markers Contributing to Pathogenesis of Candida albicans.

Abstract

The emergence of Candida albicans as a life-threatening pathogen and its resistance to available antifungal drugs is a significant global health concern. Previous findings have established that the ubiquitin mutations UbEP42, UbL50P and UbI61T interfere with morphogenesis of C. albicans from commensal yeasts to pathogenic hyphae. The main objective of this study is to investigate the influence of ubiquitin mutations on the molecular markers of morphogenesis and virulence of C. albicans to identify potential targets for therapeutic intervention. The auxotrophic strain BWP17 of C. albicans was transformed by the wild-type ubiquitin gene (UbWT) and its mutants UbEP42, UbS20F, UbA46S, UbL50P and UbI61T cloned under the doxycycline-inducible promoter in the integrative plasmid pTET25-MNC. Induced expression of the mutant forms UbEP42, UbL50P, and UbI61T while inhibiting morphogenesis, reduced chitin deposition, increased β-glucan exposure on the cell wall, decreased the secretion of aspartyl protease, caused the differential expression of cyclins Cln3, Ccn1, Clb2 and certain key transcription factors compared to UbWT. However, UbS20F and UbA46S did not have any influence. These findings demonstrating the disruptive influence of UbEP42, UbL50P, and UbI61T on the levels of molecular markers of morphology and pathogenesis of C. albicans, highlight the importance of a functional ubiquitination system.