C. albicans is the predominant human fungal pathogen and frequently colonises medical devices, such as voice prostheses, as a biofilm. It is a dimorphic yeast that can switch between yeast and hyphal forms in response to environmental cues, a property that is essential during biofilm establishment and maturation. One such cue is the elevation of CO₂ levels, as observed in exhaled breath for example. However, despite the clear medical relevance, the effect of CO₂ on C. albicans biofilm growth has not been investigated to date. Here we show that physiologically relevant CO₂ elevation enhances each stage of the C. albicans biofilm-forming process: from attachment through maturation to dispersion. The effects of CO₂ are mediated via the Ras/cAMP/PKA signalling pathway and the central biofilm regulators Efg1, Brg1, Bcr1 and Ndt80. Biofilms grown under elevated CO₂ conditions also exhibit increased azole resistance, increased Sef1-dependent iron scavenging and enhanced glucose uptake to support their rapid growth. These findings suggest that C. albicans has evolved to utilise the CO₂ signal to promote biofilm formation within the host. We investigate the possibility of targeting CO₂-activated processes and propose 2-deoxyglucose as a drug that may be repurposed to prevent C. albicans biofilm formation on medical airway management implants. We thus characterise the mechanisms by which CO₂ promotes C. albicans biofilm formation and suggest new approaches for future preventative strategies.

白色念珠菌是主要的人类真菌病原体，并且经常将医疗器械（例如语音假肢）作为生物膜定殖。它是一种二态酵母，可以根据环境线索在酵母和菌丝形式之间切换，这是生物膜建立和成熟过程中必不可少的特性。一种这样的提示是 CO ₂水平的升高，例如在呼出气中观察到的。然而，尽管具有明确的医学相关性，但迄今为止尚未研究CO ₂对白色念珠菌生物膜生长的影响。在这里，我们表明生理相关的 CO ₂升高增强了白色念珠菌的每个阶段生物膜形成过程：从附着到成熟再到分散。CO ₂的作用是通过 Ras/cAMP/PKA 信号通路和中央生物膜调节剂 Efg1、Brg1、Bcr1 和 Ndt80 介导的。在升高的 CO ₂条件下生长的生物膜还表现出增加的唑类抗性、增加的 Sef1 依赖性铁清除和增加的葡萄糖摄取以支持其快速生长。这些发现表明，白色念珠菌已经进化为利用 CO ₂信号来促进宿主内的生物膜形成。我们研究了靶向 CO ₂激活过程的可能性，并提出将 2-脱氧葡萄糖作为一种可重新用于预防白色念珠菌的药物医用气道管理植入物上的生物膜形成。因此，我们描述了 CO ₂促进白色念珠菌生物膜形成的机制，并为未来的预防策略提出了新的方法。