Cited by 62Antifungal resistance and susceptibilityFungal and yeast genetics researchFungal Infections and Studies

Control of β-glucan exposure by the endo-1,3-glucanase Eng1 in Candida albicans modulates virulence

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Yang, Mengli, Solis, Norma V., Marshall, Michaela, Garleb, Rachel, Zhou, Tingting, Wang, Daidong, Swidergall, Marc, Pearlman, Eric +2 more·2022·PLOS Pathogens

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Abstract

Candida albicans is a major opportunistic pathogen of humans. It can grow as morphologically distinct yeast, pseudohyphae and hyphae, and the ability to switch reversibly among different forms is critical for its virulence. The relationship between morphogenesis and innate immune recognition is not quite clear. Dectin-1 is a major C-type lectin receptor that recognizes β-glucan in the fungal cell wall. C . albicans β-glucan is usually masked by the outer mannan layer of the cell wall. Whether and how β-glucan masking is differentially regulated during hyphal morphogenesis is not fully understood. Here we show that the endo-1,3-glucanase Eng1 is differentially expressed in yeast, and together with Yeast Wall Protein 1 (Ywp1), regulates β-glucan exposure and Dectin-1-dependent immune activation of macrophage by yeast cells. ENG1 deletion results in enhanced Dectin-1 binding at the septa of yeast cells; while eng1 ywp1 yeast cells show strong overall Dectin-1 binding similar to hyphae of wild-type and eng1 mutants. Correlatively, hyphae of wild-type and eng1 induced similar levels of cytokines in macrophage. ENG1 expression and Eng1-mediated β-glucan trimming are also regulated by antifungal drugs, lactate and N-acetylglucosamine. Deletion of ENG1 modulates virulence in the mouse model of hematogenously disseminated candidiasis in a Dectin-1-dependent manner. The eng1 mutant exhibited attenuated lethality in male mice, but enhanced lethality in female mice, which was associated with a stronger renal immune response and lower fungal burden. Thus, Eng1-regulated β-glucan exposure in yeast cells modulates the balance between immune protection and immunopathogenesis during disseminated candidiasis.

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  1. [16]Lin J, Wester MJ, Graus MS, Lidke KA, Neumann AK. Nanoscopic cell-wall architecture of an immunogenic ligand in Candida albicans during antifungal drug treatment. Lippincott-Schwartz J, editor. Mol Biol Cell. 2016; 27: 1002– 1014. doi: 10.1091/mbc.E15-06-0355 26792838 PMC4791122 · DOI

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Authors
Yang, M., Solis, N. V., Marshall, M., Garleb, R., Zhou, T., Wang, D., Swidergall, M., Pearlman, E., Filler, S. G., & Liu, H.
Affiliations
  • University of California, Irvine (US)
  • University of California, Los Angeles (US)
  • Amgen (United States) (US)
Corresponding author
Liu, Haoping
Venue
PLOS Pathogens
Published
2022-01-07
Volume
18
Issue
1
Pages
e1010192
ISSN
  • 1553-7366 (ISSN-L)
  • 1553-7374
OpenAlex
W4206403554
Cited by
62
References
77
Citations by year
2026: 13 · 2025: 12 · 2024: 17 · 2023: 7 · 2022: 9 · 2021: 4
FWCI
5.50
Type
journal article
Language
en
Open access
Locations
  • PLoS Pathogens (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • National Institute of General Medical Sciences (R01GM117111)
  • National Institute of Allergy and Infectious Diseases (R01AI124566)
  • National Institute of Dental and Craniofacial Research (R01DE026600)
  • National Eye Institute (R01EY18612)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
  • Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
Keywords
Candida albicans, Dectin-1, fungal virulence, hyphal morphogenesis, systemic candidiasis, sex differences in susceptibility, innate immune recognition, lactate, N-acetylglucosamine, septa
MeSH terms
Animals, Candida albicans, Candidiasis, Glucan Endo-1,3-beta-D-Glucosidase, Female, Male, Mice, Inbred C57BL, Virulence, beta-Glucans, Mice

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