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CO2 enhances the formation, nutrient scavenging and drug resistance properties of C. albicans biofilms

Pentland, Daniel R., Davis, Jack, Mühlschlegel, Fritz A., Gourlay, Campbell W. (2021) CO2 enhances the formation, nutrient scavenging and drug resistance properties of C. albicans biofilms. npj Biofilms and Microbiomes, 7 (1). Article Number 67. ISSN 2055-5008. (doi:10.1038/s41522-021-00238-z) (KAR id:89882)

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https://doi.org/10.1038/s41522-021-00238-z

Abstract

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.

Item Type: Article
DOI/Identification number: 10.1038/s41522-021-00238-z
Uncontrolled keywords: Biofilm Candida Yeast Mycology CO2
Subjects: Q Science
Divisions: Divisions > Division of Natural Sciences > Biosciences
Signature Themes: Future Human, Food Systems, Natural Resources and Environment
Funders: [UNSPECIFIED] Kent Cancer Trust
Depositing User: Campbell Gourlay
Date Deposited: 23 Aug 2021 11:40 UTC
Last Modified: 24 Aug 2021 10:55 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/89882 (The current URI for this page, for reference purposes)
Gourlay, Campbell W.: https://orcid.org/0000-0002-2373-6788
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