AUTHOR=Li Shui-Xiu , Song Yan-Jun , Zhang Yi-Shan , Wu Hao-Tian , Guo Hui , Zhu Kun-Ju , Li Dong-Mei , Zhang Hong 

TITLE=Mitochondrial Complex V α Subunit Is Critical for Candida albicans Pathogenicity through Modulating Multiple Virulence Properties

JOURNAL=Frontiers in Microbiology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2017.00285

DOI=10.3389/fmicb.2017.00285

ISSN=1664-302X

ABSTRACT=<p>The α subunit (<italic>ATP1</italic>) is a vital component of mitochondrial complex V which counts for the majority of cellular ATP production in a living organism. Nevertheless, how the α subunit influences other cellular processes such as pathogenicity in <italic>Candida albicans</italic> remains poorly understood. To address this question, <italic>ATP1</italic> mutant (<italic>atp1</italic>Δ/Δ) and the gene-reconstituted strain (<italic>atp1</italic>Δ<italic>/ATP1</italic>) have been constructed in this study and their pathogenicity-related traits are compared to those of wild type (WT). In a murine model of disseminated candidiasis, <italic>atp1</italic>Δ/Δ infected mice have a significantly higher survival rate and experience a lower fungal burden in tissues. In <italic>in vitro</italic> studies <italic>atp1</italic>Δ/Δ lose a capability to damage or destroy macrophages and endothelial cells. Furthermore, <italic>atp1</italic>Δ/Δ is not able to grow under either glucose-denial conditions or high H<sub>2</sub>O<sub>2</sub> conditions, both of which are associated with the potency of the macrophages to kill <italic>C. albicans</italic>. Defects in filamentation and biofilm formation may impair the ability of <italic>atp1</italic>Δ/Δ to penetrate host cells and establish robust colonies in the host tissues. In concert with these pathogenic features, intracellular ATP levels of <italic>atp1</italic>Δ/Δ can drop to 1/3 of WT level. These results indicate that the α subunit of Complex V play important roles in <italic>C. albicans</italic> pathogenicity.</p>