Candida auris MNN1 contributes to human neutrophil evasion via mechanisms independent of β-glucan unmasking

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, mnn1 Δ, did not exhibit increased exposure of β-glucan. Nuclear magnetic resonance analysis of mnn1 Δ 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 mnn1 Δ. 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 .