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. 2021 Sep 5;7(9):725.
doi: 10.3390/jof7090725.

Immunopathogenesis of Emerging Candida auris and Candida haemulonii Strains

Sujiraphong Pharkjaksu  1 , Nawarat Boonmee  2 , Chalermchai Mitrpant  2 , Popchai Ngamskulrungroj  1
Affiliations

Immunopathogenesis of Emerging Candida auris and Candida haemulonii Strains

Sujiraphong Pharkjaksu et al. J Fungi (Basel). .

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.

Keywords: emerging Candida; innate immune response; multidrug resistance; zebrafish.

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Conflict of interest statement

All authors declare that there are no conflicts of interest related to this study. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Differing thermotolerances of Candida albicans, C. auris, and C. haemulonii. Sabouraud dextrose agar plates showing growth of representative Candida strains after 48 h incubation at 30–42 °C with serial dilution spots. Top row: C. albicans ATCC24433 as the control strain; middle row: C. auris strain SI-18-CAU-HEM; and bottom row: C. haemulonii strain SI-21-CH-PLF.
Figure 2
Figure 2
Emerging Candida virulence in a zebrafish model. Each experimental group of 26 zebrafish was injected with 107 CFU cells of one of the C. albicans ATCC24433 (control) strain, C. auris strain SI-18-CAU-HEM, or C. haemulonii strain SI-21-CH-PLF. Each experiment was performed in duplicate.
Figure 3
Figure 3
Fungal burden in zebrafish model. Each experimental group of five zebrafish was injected with 107 cells of one of the C. albicans ATCC24433 (control) strain, C. auris strain SI-18-CAU-HEM, and C. haemulonii strain SI-21-CH-PLF. Each experiment was performed in triplicate. Abbreviations and symbols: CFU/mL, colony forming unit per milliliter; ****, p < 0.0001.
Figure 4
Figure 4
The expression levels of il1b, il10, il17a, mmp9, foxp3a, and foxp3b in zebrafish infected with emerging Candida strains, by timepoint. Each experimental group of 20 zebrafish was injected with 107 CFU cells of one of the C. auris strain SI-18-CAU-HEM or the C. haemulonii strain SI-21-CH-PLF. The normalized ratios of expression were calculated by comparison with the level of expression of the β-actin gene in each group at 8 hpi. Each experiment was performed in triplicate. Abbreviations and symbols: hpi, hour-post-infection; *, p < 0.5; **, p < 0.01; ***, p < 0.001; ****, p < 0.0001.
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