| Summary: | The emergence of a multidrug-resistant <i>Candida</i> species, <i>C. auris</i> and <i>C. haemulonii</i>, 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 <i>C. albicans</i> 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 <i>C. auris</i> tolerated high temperatures, like <i>C. albicans</i>. In a zebrafish swim-bladder-inoculation model, the <i>C. auris</i>-infected group had the highest mortality rate and infectivity, suggesting the highest virulence. The case fatality rates of <i>C. auris</i>, <i>C. haemulonii,</i> and <i>C. albicans</i> were 100%, 83.33%, and 51.52%, respectively. Further immunological studies revealed that both emerging <i>Candida</i> species stimulated genes involved in the proinflammatory cytokine group. Interestingly, the genes relating to leukocyte recruitment were downregulated only for <i>C. auris</i> infections. Almost all immune response genes to <i>C. auris</i> had a peak response at an early infection time, which contrasted with <i>C. haemulonii</i>. 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.
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