Mechanisms of pathogenicity for the emerging fungus Candida auris

Abstract

Candida auris recently emerged as an urgent public health threat, causing outbreaks of invasive infections in healthcare settings throughout the world. This fungal pathogen persists on the skin of patients and on abiotic surfaces despite antiseptic and decolonization attempts. The heightened capacity for skin colonization and environmental persistence promotes rapid nosocomial spread. Following skin colonization, C. auris can gain entrance to the bloodstream and deeper tissues, often through a wound or an inserted medical device, such as a catheter. C. auris possesses a variety of virulence traits, including the capacity for biofilm formation, production of adhesins and proteases, and evasion of innate immune responses. In this review, we highlight the interactions of C. auris with the host, emphasizing the intersection of laboratory studies and clinical observations.

Fig 1. Candida auris mechanisms of pathogenesis.

C. auris colonizes and persists on the skin, and breaches of the skin barrier can lead to invasive candidiasis and hematogenous spread of infection. Interactions with other skin microbiota (e.g., Malassezia spp., Klebsiella pneumoniae, Staphylococcus hominis) influence the growth of C. auris on the skin. Biofilm formation of C. auris increases resistance to antimicrobial treatment on the skin surface. C. auris produces multiple virulence factors to release into the surrounding microenvironment including SAPs and EVs. Adhesins promote attachment to the skin surface, and mannans in the cell wall mask β-glucans from PRRs on immune cells. C. auris evades neutrophil recognition and phagocytosis. C. auris escapes macrophage killing, inhibits macrophage-mediated immune recruitment, and induces macrophage cell death. In contrast, the Th17 T-cell response inhibits C. auris skin colonization. The figure was designed using Biorender. EV, extracellular vesicle; PRR, pathogen recognition receptor; SAP, secreted aspartyl protease.

Fig 2. Skin colonization and catheter-associated infection models for C. auris.

(A) C. auris growing on the surface of porcine skin ex vivo, reproduced from Horton and colleagues [37]; measurement bar represents 10 μm. (B) C. auris replicating in the hair follicle of an immunosuppressive murine model of C. auris skin colonization, reproduced from Huang and colleagues [35]; measurement bar represents 50 μm. (C) C. auris growing as a biofilm on the luminal surface of a rat vascular catheter, reproduced from Dominguez and colleagues; measurement bar represents 5 μm [62].