Recent gene selection and drug resistance underscore clinical adaptation across Candida species.

Understanding how microbial pathogens adapt to treatments, humans and clinical environments is key to infer mechanisms of virulence, transmission and drug resistance. This may help improve therapies and diagnostics for infections with a poor prognosis, such as those caused by fungal pathogens, including Candida. Here we analysed genomic variants across approximately 2,000 isolates from six Candida species (C. glabrata, C. auris, C. albicans, C. tropicalis, C. parapsilosis and C. orthopsilosis) and identified genes under recent selection, suggesting a highly complex clinical adaptation. These involve species-specific and convergently affected adaptive mechanisms, such as adhesion. Using convergence-based genome-wide association studies we identified known drivers of drug resistance alongside potentially novel players. Finally, our analyses reveal an important role of structural variants and suggest an unexpected involvement of (para)sexual recombination in the spread of resistance. Our results provide insights on how opportunistic pathogens adapt to human-related environments and unearth candidate genes that deserve future attention.