Roles of VPH2 and VMA6 in localization of V-ATPase subunits, cell wall functions and filamentous development in Candida albicans

The vacuolar-type H+-ATPase (V-ATPase) is known to be associated with various cellular processes. Several V-ATPase subunits have been identified in C. albicans. However, there are still a few V-ATPase subunits and assembly factors that remain uncharacterized. In this study, we identified one of putative V-ATPase assembly factors, Vph2, and V0 subunit, Vma6, and explored their potential functions in C. albicans. Our results revealed that Vph2 and Vma6 were required for the correct distribution of V0 subunit Vph1 and V1 subunit Tfp1. Furthermore, Vph2 and Vma6 played an important role in endocytosis and vacuolar acidification. Disruption of VPH2 or VMA6 affected cell wall stress resistance and composition, accompanying induction of cell wall integrity (CWI) pathway. Besides, deletion of VPH2 or VMA6 led to weakened hyphal development in Spider medium that was not dependent on Hog1 activation. Moreover, the vph2Δ/Δ and vma6Δ/Δ mutants displayed attenuated virulence in a mouse model of systemic candidiasis. Taken together, our data indicated that Vph2 and Vma6 were essential for the proper localization of V-ATPase subunits, cell wall functions, filamentous growth and C. albicans pathogenesis, and provided the potential to better exploit V-ATPase-related proteins as antifungal targets.