Distinct properties of human pathogenic <i>Candida</i> species revealed by systematic comparative phenotypic screening of clinical isolates

Human-associated fungi include multiple <i>Candida</i> species whose persistence relies on phenotypic plasticity enabling adherence, stress resistance, and biofilm formation. Yet, the extent of phenotypic variation within and across species remains poorly defined. We profiled 1,366 clinical isolates from 13 <i>Candida</i> species using high-throughput quantitative fitness assays under environmental stress, antifungal exposure, and biofilm-inducing conditions. The analysis uncovered both conserved and species-specific adaptive traits. Isolates segregated into three major phenotypic archetypes: heat-resistant fast growers, osmo-sensitive strains, and slow growers. A consistent inverse correlation emerged between basal growth rate and stress resistance, revealing a fundamental physiological trade-off. Species-specific resistance signatures further reflected ecological specialization and divergent adaptive trajectories. Our quantitative framework establishes, for the first time, a comparative phenotypic landscape across a multispecies collection of human-associated <i>Candida</i>, providing new insights into their ecological specialization and adaptive strategies.