Human β defensins-1, an antimicrobial peptide, kills Candida glabrata by generating oxidative stress and arresting the cell cycle in G0/G1 phase.

Biomed Pharmacother

Center of excellence in Bionanoscience Research, King Abdulaziz University, Jeddah 21589, Saudi Arabia; Department of Clinical Microbiology and Infectious Diseases, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; Division of Infection Control, Charlotte Maxeke Johannesburg Academic Hospital, National Health Laboratory Service, Johannesburg, South Africa. Electronic address:

Published: October 2022

Candida glabrata is the most frequently isolated non-albicans Candida species in clinical samples and is known to develop resistance to commonly used antifungal drugs. Human β defensins (hBDs) are antimicrobial peptides of immune systems and are active against a broad range of pathogens including Candida species. Herein, the antifungal effect of hBD-1 and its mechanism of action in C. glabrata was studied. The antifungal susceptibility of hBD-1 against C. glabrata was calculated by broth microdilution assay. To study the mechanism of antifungal action, the impact of hBD-1 on cell cycle, expression of oxidative stress enzymes, and membrane disintegration were assessed. The susceptibility results confirmed that hBD-1 possessed the minimum inhibitory concentration of 3.12 µg/mL and prevented the growth and caused yeast cell death to various extents. The peptide at subinhibitory and inhibitory concentrations blocked the cell cycle in C. glabrata in G0/G1 phase and disturbed the activity of primary and secondary antioxidant enzymes. Furthermore, at higher concentrations disruption of membrane integrity was observed. Altogether, hBD-1 showed candidicidal activity against C. glabrata and was able to induce oxidative stress and arrested cell cycle in C. auris and therefore has a potential to be developed as an antifungal drug against C. glabrata.

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Source
http://dx.doi.org/10.1016/j.biopha.2022.113569DOI Listing

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