Adapting to the Host: Physiological Responses, Cell Wall Remodeling, and Persistence in Non-albicans Candida Species

Non-albicans Candida (NAC) species have emerged as clinically important opportunistic pathogens with distinct ecological, physiological, and pathogenic traits. Successful colonization and infection require these yeasts to survive within heterogeneous and continuously changing host microenvironments, where they encounter multiple and often simultaneous challenges. This review comparatively examines the adaptive responses of Nakaseomyces glabratus, Candida parapsilosis, Candida tropicalis, Candida auris, and Pichia kudriavzevii to major host-derived pressures, including thermal stress, nutrient restriction, fluctuations in oxygen availability and pH, and oxidative and nitrosative stress. Although exposed to similar environmental constraints, these species differ in how they integrate responses involving metabolic reprogramming, stress response mechanisms, cellular homeostasis, and structural modifications. Particular attention is given to cell wall remodeling as a dynamic interface linking environmental adaptation with adhesion, biofilm formation, immune recognition, and antifungal susceptibility. We further discuss how sustained adaptive responses may contribute to persistence and antifungal tolerance, thereby promoting fungal survival and complicating therapeutic eradication. Collectively, the pathogenic success of NAC species extends beyond classical virulence factors and depends on their capacity to dynamically adjust their physiology to host-imposed constraints, with both shared and species-specific strategies ultimately favoring survival and persistence during infection across diverse host niches under conditions of sustained therapeutic pressure.