Transcriptomic insights into <i>Candida albicans</i> adaptation to an anaerobic environment

<i>Candida albicans</i> is a clinically significant fungal pathogen capable of adapting to diverse host environments, including steep oxygen gradients ranging from ~21% oxygen to anaerobic. The ability to withstand varied oxygen levels is paramount to establishing colonization and persisting in host niches, and oxygen deprivation can also augment antifungal resistance. In this study, we used RNA sequencing to compare the global transcriptomic profiles of two strains of <i>C. albicans</i> (SC5314 and CHN1) grown purely anaerobically to those grown aerobically. In <i>C. albicans</i> SC5314, we observed a strong induction of the alternative oxidase <i>AOX2</i> and several genes encoding subunits of mitochondrial enzyme complexes I, II, and V, signifying a shift to alternative respiration. Consistent with the diminished ATP production from this process, there was a significant downregulation of genes associated with growth and metabolism, including histones and ribosomal proteins, as well as chitinases and other genes involved in cell wall remodeling. Interestingly, the anaerobic <i>C. albicans</i> cultures had decreased expression of candidalysin (<i>ECE1</i>) and other virulence factors, contrasting with other studies reporting enhanced pathogenicity under oxygen deprivation. There were a greater number of significantly upregulated genes in <i>C. albicans</i> CHN1 compared to SC5314; however, most of the top 50 upregulated genes under anaerobic conditions were consistent between the two strains. The predominant difference in down-regulated genes between the two strains could be mapped to differences in hyphal transformation under aerobic conditions. Overall, our study provides a window into the molecular mechanisms of <i>C. albicans</i> adaptation between aerobic to anaerobic environments.IMPORTANCE<i>Candida albicans</i> is a leading cause of fungal infections in humans, posing significant clinical challenges due to its remarkable adaptability and increasing antifungal resistance. Anaerobic environments can promote antifungal resistance, necessitating a deeper understanding of how <i>C. albicans</i> adapts to anoxia. While much research has been done to identify mechanisms underlying adaptation to hypoxia (i.e., low oxygen), this is the first study evaluating the global transcriptomic response of <i>C. albicans</i> to anoxia (no oxygen). Here, we uncover key transcriptomic changes that enable <i>C. albicans</i> to survive in the absence of oxygen, which are distinct from those identified under hypoxic conditions. Our research addresses a gap in current knowledge that may be exploited for combatting antifungal resistance.