Impact of secreted glucanases upon the cell surface and fitness of Candida albicans during colonisation and infection.

Qinxi Ma, Arnab Pradhan, Ian Leaves, Emer Hickey, Elena Roselletti, Ivy Dambuza, Daniel E Larcombe, Leandro Jose de Assis, Duncan Wilson, Lars P Erwig, Mihai G Netea, Delma S Childers, Gordon D Brown, Neil A R Gow, Alistair J P Brown* (Corresponding Author)

*Corresponding author for this work

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Abstract

Host recognition of the pathogen-associated molecular pattern (PAMP), β-1,3-glucan, plays a major role in antifungal immunity. β-1,3-glucan is an essential component of the inner cell wall of the opportunistic pathogen Candida albicans. Most β-1,3-glucan is shielded by the outer cell wall layer of mannan fibrils, but some can become exposed at the cell surface. In response to host signals such as lactate, C. albicans shaves the exposed β-1,3-glucan from its cell surface, thereby reducing the ability of innate immune cells to recognise and kill the fungus. We have used sets of barcoded xog1 and eng1 mutants to compare the impacts of the secreted β-glucanases Xog1 and Eng1 upon C. albicans in vitro and in vivo. Flow cytometry of Fc-dectin-1-stained strains revealed that Eng1 plays the greater role in lactate-induced β-1,3-glucan masking. Transmission electron microscopy and stress assays showed that neither Eng1 nor Xog1 are essential for cell wall maintenance, but the inactivation of either enzyme compromised fungal adhesion to gut and vaginal epithelial cells. Competitive barcode sequencing suggested that neither Eng1 nor Xog1 strongly influence C. albicans fitness during systemic infection or vaginal colonisation in mice. However, the deletion of XOG1 enhanced C. albicans fitness during gut colonisation. We conclude that both Eng1 and Xog1 exert subtle effects on the C. albicans cell surface that influence fungal adhesion to host cells and that affect fungal colonisation in certain host niches.

Original languageEnglish
Article number100128
Number of pages13
JournalThe Cell Surface
Volume11
Early online date24 Jun 2024
DOIs
Publication statusPublished - 24 Jun 2024

Bibliographical note

Acknowledgements
We thank Raif Yuecel and Attila Bebes in the Exeter Centre for Cytomics for their help with the cytometry, and Annie Phillips-Brookes, Jamie Harvey and the BSU staff for their support with the animal experimentation. We are grateful to Karen Moore, Paul O’Neill and Jemima Onime in the University of Exeter Sequencing Facility University of Exeter Sequencing Facility for their help with the barcode sequencing. We also thank Paulina Cherek in the Bioimaging Facility in Exeter Biosciences for her help with the transmission electron microscopy, and Darren Thomson in the MRC Centre for Medical Mycology for his support for our the DeltaVision imaging.

For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.

Data Availability Statement

The authors declare that the data supporting the findings of this study are available within the paper (and the accompanying Supplementary Information Files).

Keywords

  • Candida albicans
  • Cell wall
  • Eng1 endoglucanase
  • Gut colonisation
  • Virulence
  • Xog1 exoglucanase
  • β-glucan shaving

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