Mitochondrial Complex V α Subunit Is Critical for Pathogenicity through Modulating Multiple Virulence Properties.

The α subunit () 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 remains poorly understood. To address this question, mutant (Δ/Δ) and the gene-reconstituted strain (Δ) 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, Δ/Δ infected mice have a significantly higher survival rate and experience a lower fungal burden in tissues. In studies Δ/Δ lose a capability to damage or destroy macrophages and endothelial cells. Furthermore, Δ/Δ is not able to grow under either glucose-denial conditions or high HO conditions, both of which are associated with the potency of the macrophages to kill . Defects in filamentation and biofilm formation may impair the ability of Δ/Δ to penetrate host cells and establish robust colonies in the host tissues. In concert with these pathogenic features, intracellular ATP levels of Δ/Δ can drop to 1/3 of WT level. These results indicate that the α subunit of Complex V play important roles in pathogenicity.