CO₂enhances the ability ofCandida albicansto form biofilms, overcome nutritional immunity and resist antifungal treatment

Abstract

C. albicans is the predominant fungal pathogen of humans and frequently colonises medical devices, such as voice prosthesis, 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.. However, despite the clear medical relevance, the effects 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 to maturation and 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, tolerance to nutritional immunity 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.

Efeito do extrato hidroalcoólico de Phyllanthus niruri L. (quebra-pedra) sobre células planctônicas e em biofilme de Candida albicans

“…Porém, diversos autores consideram como biofilme maduro aquele que pode ser vizualizado a olho nu em superfícies. Em pesquisas, os biofilmes crescidos de 24 horas a 48 horas são considerados como maduro, sendo mais comumente utilizado o biofilme de 24 horas nos ensaios laboratoriais (Nobile & Johnson, 2015;Gulati & Nobile, 2016;Yan et al, 2019, Pentland et al, 2020. Os biofilmes de Candida também apresentam o caráter de se adaptar a diferentes condições de temperatura e pH, além de expressar adesinas, proteases e fosfolipases (Santana et al, 2013).…”