Nature of b-1,3-Glucan-Exposing Features on Candida albicans Cell Wall and Their Modulation

Leandro José de Assis* (Corresponding Author), Judith M. Bain, Corin Liddle, Ian Leaves, Christian Hacker, Roberta Peres da Silva, Raif Yuecel, Attila Bebes, David Stead, Delma S. Childers, Arnab Pradhan, Kevin Mackenzie, Katherine Lagree, Daniel E. Larcombe, Qinxi Ma, Gabriela Mol Avelar, Mihai G. Netea, Lars P. Erwig, Aaron P. Mitchell, Gordon D. BrownNeil A.R. Gow, Alistair J.P. Brown* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)
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Candida albicans exists as a commensal of mucosal surfaces and the gastrointestinal tract without causing pathology. However, this fungus is also a common cause of mucosal and systemic infections when antifungal immune defenses become compromised. The activation of antifungal host defenses depends on the recognition of fungal pathogen-associated molecular patterns (PAMPs), such as b-1,3-glucan. In C. albicans, most b-1,3-glucan is present in the inner cell wall, concealed by the outer mannan layer, but some b-1,3-glucan becomes exposed at the cell surface. In response to host signals, such as lactate, C. albicans induces the Xog1 exoglucanase, which shaves exposed b-1,3-glucan from the cell surface, thereby reducing phagocytic recognition. We show here that b-1,3-glucan is exposed at bud scars and punctate foci on the lateral wall of yeast cells, that this exposed b-1,3-glucan is targeted during phagocytic attack, and that lactate-induced masking reduces b-1,3-glucan exposure at bud scars and at punctate foci. b-1,3-Glucan masking depends upon protein kinase A (PKA) signaling. We reveal that inactivating PKA, or its conserved downstream effectors, Sin3 and Mig1/Mig2, affects the amounts of the Xog1 and Eng1 glucanases in the C. albicans secretome and modulates b-1,3-glucan exposure. Furthermore, perturbing PKA, Sin3, or Mig1/Mig2 attenuates the virulence of lactate-exposed C. albicans cells in Galleria. Taken together, the data are consistent with the idea that b-1,3-glucan masking contributes to Candida pathogenicity. IMPORTANCE Microbes that coexist with humans have evolved ways of avoiding or evading our immunological defenses. These include the masking by these microbes of their “pathogen-associated molecular patterns” (PAMPs), which are recognized as “foreign” and used to activate protective immunity. The commensal fungus Candida albicans masks the proinflammatory PAMP b-1,3-glucan, which is an essential component of its cell wall. Most of this b-1,3-glucan is hidden beneath an outer layer of the cell wall on these microbes, but some can become exposed at the fungal cell surface. Using high-resolution confocal microscopy, we examine the nature of the exposed b-1,3-glucan at C. albicans bud scars and at punctate foci on the lateral cell wall, and we show that these features are targeted by innate immune cells. We also reveal that downstream effectors of protein kinase A (Mig1/Mig2, Sin3) regulate the secretion of major glucanases, modulate the levels of b-1,3-glucan exposure, and influence the virulence of C. albicans in an invertebrate model of systemic infection. Our data support the view that b-1,3-glucan masking contributes to immune evasion and the virulence of a major fungal pathogen of humans.

Original languageEnglish
Article numbere02605-22
Number of pages19
Issue number6
Early online date11 Oct 2022
Publication statusPublished - 20 Dec 2022

Bibliographical note

Funding Information:
This work was supported by a programme grant from the UK Medical Research Council (MR/M026663/1; MR/M026663/2) and by the Medical Research Council Centre for Medical Mycology (MR/N006364/1; MR/N006364/2). NARG acknowledges Wellcome support for a Senior Investigator (101873/Z/13/Z), Collaborative (200208/A/15/Z; 215599/Z/19/Z) and Strategic Awards (097377/Z11/Z). MGN was supported by an ERC Advanced Grant (833247) and a Spinoza Grant of the Netherlands Organization for Scientific Research.

Data Availability Statement

Supplemental material is available online only.


  • β-1,3-glucan
  • Candida albicans
  • cell wall
  • Eng1
  • Mig1
  • Mig2
  • protein kinase A
  • Sin3
  • Xog1


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