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2,4-Diacetylphloroglucinol Against Candida albicans: Biofilm Formation, Aspartyl Protease Production and Ultrastructure Changes

Artyom A. Stepanov, Alexey S. Vasilchenko
doi: https://doi.org/10.1101/2022.04.26.489565
Artyom A. Stepanov
Laboratory of antimicrobial resistance, Institute of Environmental and Agricultural Biology (X-BIO), Tyumen State University, Volodarskogo street, 6, 625003, Tyumen, Russia
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Alexey S. Vasilchenko
Laboratory of antimicrobial resistance, Institute of Environmental and Agricultural Biology (X-BIO), Tyumen State University, Volodarskogo street, 6, 625003, Tyumen, Russia
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  • For correspondence: avasilchenko@gmail.com
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Abstract

The dimorphic fungus Candida albicans is the one of the most important opportunistic pathogen of human. The use of fungicides against candida encounters sub-inhibitory effects, which are fungal stress response and undesirable for the host. In this work we investigated antifungal action of 2,4-diacetylphloroglucinol against Candida albicans ATCC 10231 with focus on they biofilm forming ability under the treatment.

It was found that 2,4-DAPG reduced ability of candida cells to form biofilm, but complete inhibition or irradiation did not achieve. Moreover, Candida albicans cells in the adherent state have been characterized by reduced susceptibility to 2,4-DAPG comparing to planktonic cells.

Investigation of mechanisms which could be explain the antibiofilm action of 2,4-DAPG has revealed the reduction in cell’s surface hydrophobicity and inhibition of yeast-to-hyphae transition. Biofilms formed under the sub-inhibitory concentrations of 2,4-DAPG were depleted in protein and carbohydrate content. Furthermore, we microscopically visualized the treated biofilms and have revealed numerous cannels localized on hyphae and associated with secretion of aspartyl proteases (Sap).

We assumed what excretion of Sap is triggered by reactive oxygen generated upon affecting of mitochondrion respiration by 2,4-DAPG. Introducing of antioxidant Trolox simultaneously with 2,4-DAPG lead to reducing of Sap production. Thus, production of aspartyl proteases is a one of undesirable side effect of Candida albicans treatment, but using 2,4-DAPG in combination with antioxidants is the solution to overcome it.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted April 26, 2022.
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2,4-Diacetylphloroglucinol Against Candida albicans: Biofilm Formation, Aspartyl Protease Production and Ultrastructure Changes
Artyom A. Stepanov, Alexey S. Vasilchenko
bioRxiv 2022.04.26.489565; doi: https://doi.org/10.1101/2022.04.26.489565
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2,4-Diacetylphloroglucinol Against Candida albicans: Biofilm Formation, Aspartyl Protease Production and Ultrastructure Changes
Artyom A. Stepanov, Alexey S. Vasilchenko
bioRxiv 2022.04.26.489565; doi: https://doi.org/10.1101/2022.04.26.489565

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