Candida auris MNN1 contributes to human neutrophil evasion via mechanisms independent of β-glucan unmasking
4 affiliations
- 1Department of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA
- 2Department of Medical Microbiology & Immunology, University of Wisconsin-Madison, Madison, Wisconsin, USA
- 3Department of Surgery, Quillen College of Medicine, Center for Inflammation, Infectious Disease, and Immunity, East Tennessee State University, Johnson City, Tennessee, USA
- 4Department of Biomedical Sciences, Quillen College of Medicine, Center for Inflammation, Infectious Disease, and Immunity, East Tennessee State University, Johnson City, Tennessee, USA
Abstract
Systemic Candida (Candidozyma) auris infections can have mortality rates up to 60%, and little is known about immune responses to this fungal pathogen. Neutrophils play a major role in immunity to many fungal pathogens, including Candida species. However, neutrophils internalize C. auris at a lower rate than C. albicans. We previously found that the C. auris cell wall mannan blocks access to β-glucan, an immunostimulatory motif. Here, we analyzed the immune-evasion properties of C. auris mannan separate from glucan masking. We generated eight mannosylation mutants and identified two with increased rates of phagocytosis by human neutrophils. One of these mutants, mnn1Δ, did not exhibit increased exposure of β-glucan. Nuclear magnetic resonance analysis of mnn1Δ mannan showed decreased α-1,3-mannose linkages and acid-labile side chains. These structural changes increased the affinity of human Dectin-2 and Mincle for mannans in vitro, and Fab blocking of Dectin-2 decreased human neutrophil phagocytosis of mnn1Δ. Overall, our work provides insight into human neutrophil recognition of C. auris mannans and further understanding of mechanisms of immune evasion for this fungal pathogen.
IMPORTANCE: Cell surface glycan recognition plays an important role in the innate immune response to fungal pathogens. Here, we use Candida auris mannosylation mutants to identify C. auris genes that contribute to its neutrophil evasion properties. We identify a mannosylation gene, MNN1, that contributes to human and murine peripheral blood neutrophil evasion without significantly impacting beta-glucan masking. We attribute MNN1 to the alteration of cell surface mannans that leads to decreased Dectin-2-binding affinity. While mannan has been associated with masking β-glucan in the C. auris cell wall, the impact of specific mannan structures on receptor binding presents an additional mechanism of neutrophil evasion for C. auris.
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BibTeX
@article{holt2026candida,
title = {{Candida auris MNN1 contributes to human neutrophil evasion via mechanisms independent of β-glucan unmasking}},
author = {Ashley M. Holt and Mark V. Horton and Chad J. Johnson and Robert Zarnowski and Por Choua Vang and Megan Dean and Arianna Kaas and Brody D. Andes and Ryley Jones and Douglas Lowman and Michael D. Kruppa and Zuchao Ma and David L. Williams and Jeniel E. Nett},
journal = {mBio},
year = {2026},
month = sep,
doi = {10.1128/mbio.01701-26},
url = {https://doi.org/10.1128/mbio.01701-26},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Candida auris MNN1 contributes to human neutrophil evasion via mechanisms independent of β-glucan unmasking
AU - Ashley M. Holt
AU - Mark V. Horton
AU - Chad J. Johnson
AU - Robert Zarnowski
AU - Por Choua Vang
AU - Megan Dean
AU - Arianna Kaas
AU - Brody D. Andes
AU - Ryley Jones
AU - Douglas Lowman
AU - Michael D. Kruppa
AU - Zuchao Ma
AU - David L. Williams
AU - Jeniel E. Nett
PY - 2026
DA - 2026/09/24
JO - mBio
DO - 10.1128/mbio.01701-26
UR - https://doi.org/10.1128/mbio.01701-26
AB - Systemic Candida (Candidozyma) auris infections can have mortality rates up to 60%, and little is known about immune responses to this fungal pathogen. Neutrophils play a major role in immunity to many fungal pathogens, including Candida species. However, neutrophils internalize C. auris at a lower rate than C. albicans. We previously found that the C. auris cell wall mannan blocks access to β-glucan, an immunostimulatory motif. Here, we analyzed the immune-evasion properties of C. auris mannan separate from glucan masking. We generated eight mannosylation mutants and identified two with increased rates of phagocytosis by human neutrophils. One of these mutants, mnn1Δ, did not exhibit increased exposure of β-glucan. Nuclear magnetic resonance analysis of mnn1Δ mannan showed decreased α-1,3-mannose linkages and acid-labile side chains. These structural changes increased the affinity of human Dectin-2 and Mincle for mannans in vitro, and Fab blocking of Dectin-2 decreased human neutrophil phagocytosis of mnn1Δ. Overall, our work provides insight into human neutrophil recognition of C. auris mannans and further understanding of mechanisms of immune evasion for this fungal pathogen. IMPORTANCE: Cell surface glycan recognition plays an important role in the innate immune response to fungal pathogens. Here, we use Candida auris mannosylation mutants to identify C. auris genes that contribute to its neutrophil evasion properties. We identify a mannosylation gene, MNN1, that contributes to human and murine peripheral blood neutrophil evasion without significantly impacting beta-glucan masking. We attribute MNN1 to the alteration of cell surface mannans that leads to decreased Dectin-2-binding affinity. While mannan has been associated with masking β-glucan in the C. auris cell wall, the impact of specific mannan structures on receptor binding presents an additional mechanism of neutrophil evasion for C. auris.
SN - 2150-7511
ER -