Abstract
The emergence of a multidrug-resistant Candida species, C. auris and C. haemulonii, has been reported worldwide. In Thailand, information on them is limited. We collected clinical isolates from Thai patients with invasive candidiasis. Both species were compared with a laboratory C. albicans strain. In vitro antifungal susceptibility and thermotolerance, and pathogenesis in the zebrafish model of infection were investigated. Both species demonstrated high minimal inhibitory concentrations to fluconazole and amphotericin B. Only C. auris tolerated high temperatures, like C. albicans. In a zebrafish swim-bladder-inoculation model, the C. auris-infected group had the highest mortality rate and infectivity, suggesting the highest virulence. The case fatality rates of C. auris, C. haemulonii, and C. albicans were 100%, 83.33%, and 51.52%, respectively. Further immunological studies revealed that both emerging Candida species stimulated genes involved in the proinflammatory cytokine group. Interestingly, the genes relating to leukocyte recruitment were downregulated only for C. auris infections. Almost all immune response genes to C. auris had a peak response at an early infection time, which contrasted with C. haemulonii. In conclusion, both emerging species were virulent in a zebrafish model of infection and could activate the inflammatory pathway. This study serves as a stepping stone for further pathogenesis studies of these important emerging species.
Highlights
The Candida species are important causes of bloodstream infections in hospitalized patients
We investigated the interaction between emerging Candida strains, C. auris and C. haemulonii, exhibiting high MICs to antifungal agents and host immune response by using zebrafish as a model for an immunopathogenesis study
We studied the characteristics of the first-isolated C. auris and C. haemulonii at our hospital, and we highlighted experimental evidence to identify differences in their drug susceptibility patterns, pathogenicity, and host responses in zebrafish
Summary
The Candida species are important causes of bloodstream infections in hospitalized patients. High mortality rates among patients have been associated with a delayed initiation of appropriate antifungal treatment [3,4] This problem is compounded by the drug-resistant Candida, notably C. glabrata, found in many hospitals [5,6]. We investigated the interaction between emerging Candida strains, C. auris and C. haemulonii, exhibiting high MICs to antifungal agents and host immune response by using zebrafish as a model for an immunopathogenesis study. We found that C. auris and C. haemulonii were both highly virulent and several proinflammatory cytokine genes were involved in their pathogenesis This highlights the advantage of using the zebrafish model to determine the virulence of Candida species, and potentially to investigate these emerging drug-resistant Candida species in the future
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