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. 2024 Dec;15(1):2405000.
doi: 10.1080/21505594.2024.2405000. Epub 2024 Oct 15.

Unveiling the roles of CaSDH8 in Candida albicans: Implications for virulence and azole resistance

Mingjiao Huang  1   2 , Dongxu Song  2 , Luoxiong Zhou  3   2 , Zhenlong Jiao  2 , Longbing Yang  1 , Yang Yang  1 , Jian Peng  1   3 , Guo Guo  1   3   2
Affiliations

Unveiling the roles of CaSDH8 in Candida albicans: Implications for virulence and azole resistance

Mingjiao Huang et al. Virulence. 2024 Dec.

Abstract

Candida albicans is the most common pathogen in systemic fungal diseases, exhibits a complex pathogenic mechanism, and is increasingly becoming drug tolerant. Therefore, it is particularly important to study the genes associated with virulence and resistance of C. albicans. Here, we identified a gene (orf19.1588) that encodes a conserved mitochondrial protein known as CaSDH8, upon deletion of CaSdh8, the deleted strain (Casdh8Δ/Δ) experienced impaired growth, hyphal development, and virulence. Casdh8Δ/Δ displayed a reduced capacity to utilize alternative carbon sources, along with detrimental alterations in reactive oxygen species (ROS), mitochondrial membrane potential (MMP) depolarization, and adenosine triphosphate (ATP) levels. Interestingly, Casdh8Δ/Δ demonstrated resistance to azole drugs, and under the influence of fluconazole, the cell membrane permeability and mitochondrial function of Casdh8Δ/Δ were less compromised than those of the wild type, indicating a reduction in the detrimental effects of fluconazole on Casdh8Δ/Δ. These findings highlight the significance of CaSDH8 as a crucial gene for the maintenance of cellular homoeostasis. Our study is the first to document the effects of the CaSDH8 gene on the virulence and azole resistance of C. albicans at both the molecular and animal levels, providing new clues and directions for the antifungal infection and the discovery of antifungal drug targets.

Keywords: CRISPR-Cas9; Candida albicans; SDH8; azole resistance; mitochondria; virulence.

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Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

Figure 1.
Figure 1.
Sequence analysis and intracellular localization of CaSdh8p.
Figure 2.
Figure 2.
The growth pattern of C. albicans.
Figure 3.
Figure 3.
The virulence of Casdh8Δ/Δ in mice model of haematogenous disseminated candidiasis.
Figure 4.
Figure 4.
Analysis of mitochondrial function in Casdh8Δ/Δ.
Figure 5.
Figure 5.
Azole sensitivity of Casdh8Δ/Δ.
Figure 6.
Figure 6.
Changes of mitochondrial function, membrane permeability and efflux pump activities in Casdh8Δ/Δ under FLC stress.
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References

    1. Brown GD, Denning DW, Gow NA, et al. Hidden killers: human fungal infections. Sci Transl Med. 2012;4(165):165rv13. doi: 10.1126/scitranslmed.3004404 - DOI - PubMed
    1. Shibasaki S, Karasaki M, Aoki W, et al. Molecular and physiological study of Candida albicans by quantitative proteome analysis. Proteomes. 2018;6(3):34. doi: 10.3390/proteomes6030034 - DOI - PMC - PubMed
    1. Su S, Li X, Yang X, et al. Histone acetylation/deacetylation in Candida albicans and their potential as antifungal targets. Future Microbiol. 2020;15(11):1075–18. doi: 10.2217/fmb-2019-0343 - DOI - PubMed
    1. Kadosh D. Regulatory mechanisms controlling morphology and pathogenesis in Candida albicans. Curr Opin Microbiol. 2019;52:27–34. doi: 10.1016/j.mib.2019.04.005 - DOI - PMC - PubMed
    1. Khan F, Bamunuarachchi NI, Tabassum N, et al. Suppression of hyphal formation and virulence of Candida albicans by natural and synthetic compounds. Biofouling. 2021;37(6):626–655. doi: 10.1080/08927014.2021.1948538 - DOI - PubMed

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