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

Abstract

The newly emerged Candida species Candida auris is associated with an exponential rise in life-threatening invasive disease in health care facilities worldwide. Unlike other species, C. auris 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 in vitro biofilm evaluations and confocal laser scanning microscopy, C. auris 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 C. auris phenotypes and Candida albicans. Based on the results of microbial recovery and scanning electron microscopy analysis of explanted catheters, compared to C. albicans, C. auris more avidly adhered and formed biofilms on catheters. However, although C. auris adhered to oral tissue ex vivo, unlike C. albicans, it failed to colonize the oral cavity in vivo, as demonstrated by microbial recovery and tissue histopathology analysis. In contrast, recovery from peritoneal lavage fluid and kidneys during time course experiments demonstrated that C. auris persisted longer in the peritoneal cavity and kidneys. Although there were clear niche-specific differences in pathogenic features between C. auris and C. albicans, no significant differences were noted between the C. auris phenotypes in vivo. The combined findings highlight unique niche-specific pathogenic traits for C. auris warranting further investigations. Understanding the factors contributing to the rise of C. auris as a nosocomial pathogen is critical for controlling the spread of this species. IMPORTANCE The newly emerged Candida species C. auris has been associated with an exponential rise in invasive disease in health care facilities worldwide with a mortality rate approaching 60%. C. auris 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 C. auris and C. albicans. Findings demonstrated that C. auris adheres more avidly, forming robust biofilms on catheters implanted in mice. However, although C. auris adhered to oral tissue ex vivo, it failed to colonize the oral cavity in vivo. In contrast, in the intraperitoneal infection model, C. auris persisted longer in the peritoneal cavity and kidneys. Understanding the host-pathogen factors contributing to the rise of C. auris as a nosocomial pathogen is critical for controlling the spread of this species.

Therapeutic implications of C. albicans-S. aureus mixed biofilm in a murine subcutaneous catheter model of polymicrobial infection

“…Therefore, to substantiate our in vitro findings on enhanced S. aureus antimicrobial tolerance in mixed biofilms with C. albicans ( Figure 2 ), we modified the established mouse subcutaneous catheter model, which proved to be suitable for sustaining polymicrobial biofilm formation, as demonstrated by SEM analysis of explanted catheters ( Fig. 2 , 3) [ 45 , 50 ]. Vancomycin therapy was implemented at clinically relevant therapeutic doses over a period of five days in mice with single-species or mixed-species infected catheters.…”

“…infections and anti-biofilm strategies [45,50], one disadvantage is lack of blood flow, which can result in inefficient drug delivery to the biofilm within the catheter. In fact, an initial pilot study indicated no effect for vancomycin on S. aureus recovery from single-species biofilms, supporting this concern (data not shown), and therefore, to circumvent this problem, for the therapy experiments, the catheters were cut longitudinally prior to inoculation and implantation in the animals.…”

“…Notably, although single-species S. aureus biofilms were statistically susceptible to vancomycin treatment, the level of response was variable among the experimental sets. It is important to note however, that although the subcutaneous catheter infection model is an appropriate and reproducible model to evaluate foreign device biofilm infections and anti-biofilm strategies [ 45 , 50 ], one disadvantage is lack of blood flow, which can result in inefficient drug delivery to the biofilm within the catheter. In fact, an initial pilot study indicated no effect for vancomycin on S. aureus recovery from single-species biofilms, supporting this concern (data not shown), and therefore, to circumvent this problem, for the therapy experiments, the catheters were cut longitudinally prior to inoculation and implantation in the animals.…”

Candida Auris: Imminence of a New Pandemic?

“…Este patógeno também foi encontrado fora do ambiente hospitalar devido ao fato de conseguir sobreviver por mais tempo fora do corpo humano e em temperaturas mais altas quando comparada com outras espécies de Candida. Outros fatores que colaboram com sua disseminação foram a difícil identificação laboratorial desta espécie, sendo ela confundida algumas vezes com outros tipos de Candida, bem como sua resistência medicamentosa, levando a ineficácia do tratamento (WALL et al, 2019).…”

Isolamento e perfil de resistência de Candida spp. de animais domésticos e selvagens

“…albicans tem sido descrita como a espécie mais prevalente em infecções, no entanto, outras espécies de Candida por mecanismos patológicos e epidemiológicos também se destacam pela patogenicidade e apresentam uma resistência emergente a agentes antifúngicos como C. tropicalis, C. parapsilosis e C. guilliermondii (Cordeiro et al, 2013;Brilhante et al, 2014). Outra preocupação é o surgimento de novas espécies como por exemplo C. auris descoberta em 2009 e que se apresenta com distribuição cosmopolita, associada a quadro de doença invasiva com alta mortalidade devido a um alto nível de transmissibilidade, resistência a múltiplas drogas e persistência no ambiente (Vila et al, 2020;Chakrabarti & Singh, 2020).…”