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Candida auris , a recently emergent fungal pathogen, has caused invasive infections in health care settings worldwide. Mortality rates approach 60% and hospital spread poses a public health threat. Compared to other  Candida  spp.,  C. auris  avoids triggering the antifungal activity of neutrophils, innate immune cells that are critical for responding to many invasive fungal infections, including candidiasis. However, the mechanism underpinning this immune evasion has been largely unknown. Here, we show that  C. auris  cell wall mannosylation contributes to the evasion of neutrophils  ex vivo  and in a zebrafish infection model. Genetic disruption of mannosylation pathways ( PMR1  and  VAN1 ) diminishes the outer cell wall mannan, unmasks immunostimulatory components, and promotes neutrophil engagement, phagocytosis, and killing. Upon examination of these pathways in other  Candida  spp. ( Candida albicans  and  Candida glabrata ), we did not find an impact on neutrophil interactions. These studies show how  C. auris  mannosylation contributes to neutrophil evasion though pathways distinct from other common  Candida  spp. The findings shed light on innate immune evasion for this emerging pathogen.   IMPORTANCE  The emerging fungal pathogen  Candida auris  presents a global public health threat. Therapeutic options are often limited for this frequently drug-resistant pathogen, and mortality rates for invasive disease are high. Previous study has demonstrated that neutrophils, leukocytes critical for the antifungal host defense, do not efficiently recognize and kill  C. auris . Here, we show how the outer cell wall of  C. auris  promotes immune evasion. Disruption of this mannan polysaccharide layer renders  C. auris  susceptible to neutrophil killing  ex vivo  and in a zebrafish model of invasive candidiasis. The role of these mannosylation pathways for neutrophil evasion appears divergent from other common  Candida  species.

Candida auris Cell Wall Mannosylation Contributes to Neutrophil Evasion through Pathways Divergent from Candida albicans and Candida glabrata