Source: Medical Gas Research
Published: 2026 May
PubMed ID: 42157423
DOI: 10.4103/mgr.MEDGASRES-D-26-00038
Carbon dioxide (CO2) is a pivotal environmental signal that influences the physiology, development and pathogenic potential of fungi. Beyond its role as a metabolic by-product, CO2 functions as a conserved signaling molecule that enables fungal pathogens to sense and adapt to host niches. This review synthesizes current knowledge on how fluctuations in CO2 concentration modulate growth dynamics, morphogenesis, virulence-associated attributes and antifungal susceptibility in clinically important yeasts and filamentous fungi. In Candida species, particularly Candida albicans, physiological CO2 levels encountered in host tissues (~5%) act as a potent morphogenetic signal, driving the yeast-to-hypha transition, promoting biofilm formation and inducing metabolic reprogramming; processes tightly linked to tissue invasion and persistence. CO2 exposure also alters membrane composition and stress response pathways, thereby modulating susceptibility to antifungal agents. In Cryptococcus neoformans, elevated CO2 concentrations promote capsule biosynthesis and enlargement, alongside extensive remodeling of surface architecture and membrane composition. These CO2-driven adaptations strengthen resistance to host immune defenses and are associated with increased tolerance to antifungals. In Aspergillus species, CO2 availability influences growth, mycotoxin biosynthesis and developmental trajectories by shifting the balance between asexual and sexual reproduction, with downstream effects on virulence and antifungal responsiveness. In Scedosporium/Lomentospora species, CO2 promotes conidial germination and developmental transitions that may indirectly impact antifungal susceptibility and pathogenic fitness. Collectively, these findings highlight environmental CO2 as a pivotal and dynamic regulator of fungal biology, offering key insights into host-pathogen interactions, informing the prediction of antifungal susceptibility profiles and supporting the rational optimization of therapeutic strategies in clinical settings.