Kent Fungal Group, School of Biosciences, University of Kent, Kent, UK.
Laboratoire National de Santé, Dudelange, Luxembourg.
NPJ Biofilms Microbiomes. 2021 Aug 12;7(1):67. doi: 10.1038/s41522-021-00238-z.
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 CO levels, as observed in exhaled breath for example. However, despite the clear medical relevance, the effect of CO on C. albicans biofilm growth has not been investigated to date. Here we show that physiologically relevant CO elevation enhances each stage of the C. albicans biofilm-forming process: from attachment through maturation to dispersion. The effects of CO are mediated via the Ras/cAMP/PKA signalling pathway and the central biofilm regulators Efg1, Brg1, Bcr1 and Ndt80. Biofilms grown under elevated CO 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 CO signal to promote biofilm formation within the host. We investigate the possibility of targeting CO-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 CO 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，常以生物膜的形式定植于医疗设备，如人工语音假体。它是一种二相性酵母，可根据环境信号在酵母和菌丝形式之间转换，这种特性在生物膜形成和成熟过程中至关重要。其中一个信号是 CO 水平的升高，例如在呼出的气体中观察到的那样。然而，尽管具有明显的医学相关性，但迄今为止尚未研究 CO 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 升高增强了白色念珠菌生物膜形成过程的每个阶段：从附着到成熟再到分散。CO 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 条件下生长的生物膜也表现出增加的唑类药物抗性、增加的 Sef1 依赖性铁摄取和增强的葡萄糖摄取，以支持其快速生长。这些发现表明，白色念珠菌已经进化到利用 CO 信号来促进宿主内的生物膜形成。我们研究了靶向 CO 激活过程的可能性，并提出 2-脱氧葡萄糖可能被重新用于预防医疗气道管理植入物上的白色念珠菌生物膜形成。因此，我们描述了 CO 促进白色念珠菌生物膜形成的机制，并提出了未来预防策略的新方法。
