Fig. 1: AOX2 induction enables virulence in mice.

a Schematic depiction of the mitochondrial electron transport chain (ETC) in Candida spp. The classical cytochrome pathway (COX; in blue) is composed of Complex III, cytochrome C, and Complex IV. Alternative oxidases (Aox) mediate direct electron transport from ubiquinol (UBQ) to molecular oxygen. Both COX and AOX pathways function with Complex I, Complex II, UBQ, and Complex V (components in green) to enable oxidative phosphorylation. b Alternative oxidase supports C. albicans virulence. Mice (n = 8) were infected with the indicated C. albicans strains by retro-orbital injection, and survival was monitored for 18 days. p values were calculated by Mantel–Cox test (n = 8): aox2 vs. SC5314 (or aox2 + AOX2(B)) p = 0.0001; aox2 vs. aox2 + AOX2(A) p < 0.0001). c An aox2-deletion strain is capable of initiating infection of target organs. Groups of mice (n = 5) were euthanized 3 days after systemic infection with aox2 mutant or add-back strain (aox2 + AOX2(A)), and fungal colony-forming units (CFUs) were recovered from the indicated organs. One kidney per animal was assessed for CFUs, and the other was used for the histological analyses presented in d; <LoD: less than limit of detection; ns: not significant (p > 0.05 by unpaired two-tailed t test for each organ). d An aox2-deletion mutant stimulates greater leukocyte accumulation at sites of infection than complemented add-back strain. Immunohistochemical staining of kidney sections (Day 3 post-infection) was performed using α-Candida or α-CD45 antibody (brown signals). H&E staining of a serial section is presented for orientation. Images are presented from representative tissue sections obtained from three mice for each experimental condition. Scale bar, 0.2 mm.