Candida auris: A Decade of Understanding of an Enigmatic Pathogenic Yeast

Abstract

Candida auris is an enigmatic yeast that continues to stimulate interest within the mycology community due its rapid and simultaneous emergence of distinct clades. In the last decade, almost 400 manuscripts have contributed to our understanding of this pathogenic yeast. With dynamic epidemiology, elevated resistance levels and an indication of conserved and unique pathogenic traits, it is unsurprising that it continues to cause clinical concern. This mini-review aims to summarise some of the key attributes of his remarkable pathogenic yeast.

Keywords: Candida auris; biofilms; in vivo models; pathogenicity.

Figure 1

Summary of in vivo pathogenicity studies of Candida auris. The virulence of C. auris in comparison to various other Candida spp. has been assessed in a number of different vertebrate and invertebrate systems including Galleria mellonella (A), immunocompetent mice (B), immunocompromised mice (C), Danio rerio (D) and Drosophila melanogaster (E). Figure was created with BioRender.

Figure 2

Host-pathogen interactions of Candida auris. Candida auris evades neutrophil capture via neutrophil extracellular trap (NET) formation. Neutrophils preferentially target Candida albicans in mixed cultures with C. auris (A). Peripheral blood mononuclear cells (PBMCs) fail to induce a potent pro-inflammatory cytokine response against C. auris, whilst Candida tropicalis, Candida guilliermondii and Candida krusei induced production of TNF-α, IL-6 and IL1-β in PBMC co-cultures (B). Human monocyte-derived macrophages were shown to recognize and phagocytose C. auris (C). Anti-Als3p antibodies generated by the NDV-3A vaccine in mice significantly reduced biofilm formation capabilities in C. auris (D) and enhanced opsonophagocytic killing by murine macrophages in vitro (E). Neutropenic mice susceptible to lethal C. auris-disseminated infection were protected following Als3p vaccination. Depletion of macrophages and CD4+ T cells in this model resulted in reduced survival rates in mice, suggestive that these cell subsets play an important role in NDV-3A vaccine-mediated protection (F). Figure was created with BioRender.