Abstract
ABSTRACTCandida auris has recently emerged as the first fungal pathogen to cause a global public health threat. The reason this species is causing hospital-associated outbreaks of invasive candidiasis with high mortality is unknown. In this study, we examine the interaction of C. auris with neutrophils, leukocytes critical for control of invasive fungal infections. We show that human neutrophils do not effectively kill C. auris. Compared to Candida albicans, neutrophils poorly recruited to C. auris and failed to form neutrophil extracellular traps (NETs), which are structures of DNA, histones, and proteins with antimicrobial activity. In mixed cultures, neutrophils preferentially engaged and killed C. albicans over C. auris. Imaging of neutrophils in a zebrafish larval model of invasive candidiasis revealed the recruitment of approximately 50% fewer neutrophils in response to C. auris compared to C. albicans. Upon encounter with C. albicans in the zebrafish hindbrain, neutrophils produced clouds of histones, suggesting the formation of NETs. These structures were not observed in C. auris infection. Evasion of neutrophil attack and innate immunity offers an explanation for the virulence of this pathogen.
Highlights
Candida auris has recently emerged as the first fungal pathogen to cause a global public health threat
Unlike many fungal infections, neutropenia has not been reported as a common risk factor for C. auris infection [1, 11]
The preference of human neutrophils for C. albicans over C. auris was even more apparent for the mixed culture (Fig. 1g and h; see Movie S1 in the supplemental material)
Summary
Candida auris has recently emerged as the first fungal pathogen to cause a global public health threat. These immune cells kill fungi through phagocytosis or the release of neutrophil extracellular traps (NETs), which are structures of DNA, histones, and proteins with antimicrobial activity [8,9,10]. To determine if neutrophils effectively eradicate C. auris, we measured fungal viability after encounter with human neutrophils and included C. albicans, the most commonly isolated Candida species, for comparison (Fig. 1a).
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