Comparative Evaluations of the Pathogenesis of Candida auris Phenotypes and Candida albicans Using Clinically Relevant Murine Models of Infections

Abstract

The newly emerged <i>Candida</i> species <i>Candida auris</i> is associated with an exponential rise in life-threatening invasive disease in health care facilities worldwide. Unlike other species, <i>C. auris</i> exhibits a high level of transmissibility, multidrug resistance, and persistence in the environment, yet little is known about its pathogenesis largely due to limited data from animal models. Based on <i>in vitro</i> biofilm evaluations and confocal laser scanning microscopy, <i>C. auris</i> phenotypes with different biofilm-forming abilities were identified, indicating potential clinical implications. Using clinically relevant murine models of implanted catheter, oral, and intraperitoneal infections, we comparatively evaluated the host site-specific pathogenic potential of <i>C. auris</i> phenotypes and <i>Candida albicans</i> Based on the results of microbial recovery and scanning electron microscopy analysis of explanted catheters, compared to <i>C. albicans</i>, <i>C. auris</i> more avidly adhered and formed biofilms on catheters. However, although <i>C. auris</i> adhered to oral tissue <i>ex vivo</i>, unlike <i>C. albicans</i>, it failed to colonize the oral cavity <i>in vivo</i>, as demonstrated by microbial recovery and tissue histopathology analysis. In contrast, recovery from peritoneal lavage fluid and kidneys during time course experiments demonstrated that <i>C. auris</i> persisted longer in the peritoneal cavity and kidneys. Although there were clear niche-specific differences in pathogenic features between <i>C. auris</i> and <i>C. albicans</i>, no significant differences were noted between the <i>C. auris</i> phenotypes <i>in vivo</i> The combined findings highlight unique niche-specific pathogenic traits for <i>C. auris</i> warranting further investigations. Understanding the factors contributing to the rise of <i>C. auris</i> as a nosocomial pathogen is critical for controlling the spread of this species.<b>IMPORTANCE</b> The newly emerged <i>Candida</i> species <i>C. auris</i> has been associated with an exponential rise in invasive disease in health care facilities worldwide with a mortality rate approaching 60%. <i>C. auris</i> exhibits a high level of transmissibility, multidrug resistance, and persistence in hospital environments, yet little is known about its pathogenesis largely due to limited data from animal studies. We used clinically relevant murine models of infection to comparatively evaluate the host niche-specific pathogenic potential of <i>C. auris</i> and <i>C. albicans</i> Findings demonstrated that <i>C. auris</i> adheres more avidly, forming robust biofilms on catheters implanted in mice. However, although <i>C. auris</i> adhered to oral tissue <i>ex vivo</i>, it failed to colonize the oral cavity <i>in vivo</i> In contrast, in the intraperitoneal infection model, <i>C. auris</i> persisted longer in the peritoneal cavity and kidneys. Understanding the host-pathogen factors contributing to the rise of <i>C. auris</i> as a nosocomial pathogen is critical for controlling the spread of this species.