Pathogenicity Evaluation on Fluconazole-Resistant Candida auris Clade V in Murine Model.

Abstract

Background: Candida auris, a medically multidrug-resistant fungal pathogen, has recently emerged as the primary one that poses a global public health threat. Although C. auris was first described in Japan, numerous cases of C. auris infections have been reported globally and clustered in four major clades (I, II, III, and IV). In 2019 and 2024, a potential V clade in Iran and VI clade in Bangladesh were described. Nevertheless, limited pathogenicity data of the fifth clade are available compared to the other clades.

Objectives and methods: This study evaluated the pathogenicity of fluconazole-resistant C. auris clade V and the therapeutic efficacy of amphotericin B in an immunocompromised mouse model, with C. albicans serving as a standard pathogen. The infection's advancement was tracked by evaluating mortality rates, fungal burden, and histopathological alterations.

Results: The C. auris clade V strain exhibited the highest fungal load in heart and kidney tissues on days 3, 5, 7, and 10, with the lowest load observed in brain tissue. In contrast, mice infected with the C. albicans strain showed the highest fungal load in the spleen on days 3, 5, and 10 and in the heart on the 7th day post-infection. Conversely, the average survival time for mice infected with C. auris was 14 days with drug treatment, demonstrating that AMB treatment significantly improved the survival rate of mice infected with C. auris clade V.

Conclusion: This study highlights the differing pathogenic behaviors of C. auris clade V and C. albicans. Although C. albicans exhibits greater virulence in untreated infections, C. auris clade V remains a serious threat, even at lower colony levels. The improved survival rates in infected mice treated with amphotericin B underscore the importance of effective therapeutic interventions. Further research is essential to enhance our understanding of these pathogens and optimize treatment protocols.