Candida auris-macrophage cellular interactions and transcriptional response

ABSTRACT: The pathogenic yeast Candida auris represents a global threat of the utmost clinical relevance. This emerging fungal species is remarkable in its resistance to commonly used antifungal and its persistence in the nosocomial settings. The innate immune system is one the first lines of defense preventing the dissemination of pathogens in the host. C. auris is susceptible to circulating phagocytes, namely neutrophils. However, some gaps of knowledge remain regarding the cellular and transcriptional responses towards other phagocytic lineages. In this work, we examined the interactions of this yeast with macrophages. We found that macrophages avidly phagocytose C. auris, however intracellular replication is not inhibited, indicating that C. auris is able to resist the killing mechanisms imposed by the phagocyte. Intracellular replication does not induce macrophage lysis, however. The transcriptional response of C. auris to macrophage phagocytosis is very similar to other members of the CUG clade (C. albicans, C. tropicalis, C. parapsilosis, C. lusitaniae), i.e., downregulation of transcription/translation and upregulation of alternative carbon metabolism pathways, transporters and induction of oxidative stress response and proteolysis. Gene family expansions are common in this yeast, and we found that many of these genes are induced in response to macrophage co-incubation. Among these, amino acid and oligopeptide transporters, as well as lipases and proteases are upregulated. Thus, C. auris shares key transcriptional signatures shared with other fungal pathogens and capitalizes on the expansion of gene families coding for potential virulence attributes that allow its survival, persistence, and evasion of the innate immune system.

ORGANISM(S): Candidozyma auris

PROVIDER: GSE236004 | GEO | 2024/06/28

REPOSITORIES: GEO