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

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 Ca...

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Main Authors: Majid Rasool Kamli, Jamal S.M. Sabir, Maqsood Ahmad Malik, Aijaz Ahmad
Format: Article
Language:English
Published: Elsevier 2022-10-01
Series:Biomedicine & Pharmacotherapy
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0753332222009581
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author Majid Rasool Kamli
Jamal S.M. Sabir
Maqsood Ahmad Malik
Aijaz Ahmad
author_facet Majid Rasool Kamli
Jamal S.M. Sabir
Maqsood Ahmad Malik
Aijaz Ahmad
author_sort Majid Rasool Kamli
collection DOAJ
description 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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spelling doaj.art-6ce98668ab44465fa128b1ca239f53e02022-12-22T03:47:11ZengElsevierBiomedicine & Pharmacotherapy0753-33222022-10-01154113569Human β defensins-1, an antimicrobial peptide, kills Candida glabrata by generating oxidative stress and arresting the cell cycle in G0/G1 phaseMajid Rasool Kamli0Jamal S.M. Sabir1Maqsood Ahmad Malik2Aijaz Ahmad3Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia; Center of excellence in Bionanoscience Research, King Abdulaziz University, Jeddah 21589, Saudi Arabia; Corresponding author at: Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia.Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia; Center of excellence in Bionanoscience Research, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Chemistry, Faculty of Sciences, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi ArabiaCenter 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; Corresponding author at: Department of Clinical Microbiology and infectious Diseases, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2193, South Africa.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.http://www.sciencedirect.com/science/article/pii/S0753332222009581Candida glabrataHuman β-defensins-1Antimicrobial peptidesCell cycle arrestAntioxidant enzymes
spellingShingle Majid Rasool Kamli
Jamal S.M. Sabir
Maqsood Ahmad Malik
Aijaz Ahmad
Human β defensins-1, an antimicrobial peptide, kills Candida glabrata by generating oxidative stress and arresting the cell cycle in G0/G1 phase
Biomedicine & Pharmacotherapy
Candida glabrata
Human β-defensins-1
Antimicrobial peptides
Cell cycle arrest
Antioxidant enzymes
title Human β defensins-1, an antimicrobial peptide, kills Candida glabrata by generating oxidative stress and arresting the cell cycle in G0/G1 phase
title_full Human β defensins-1, an antimicrobial peptide, kills Candida glabrata by generating oxidative stress and arresting the cell cycle in G0/G1 phase
title_fullStr Human β defensins-1, an antimicrobial peptide, kills Candida glabrata by generating oxidative stress and arresting the cell cycle in G0/G1 phase
title_full_unstemmed Human β defensins-1, an antimicrobial peptide, kills Candida glabrata by generating oxidative stress and arresting the cell cycle in G0/G1 phase
title_short Human β defensins-1, an antimicrobial peptide, kills Candida glabrata by generating oxidative stress and arresting the cell cycle in G0/G1 phase
title_sort human β defensins 1 an antimicrobial peptide kills candida glabrata by generating oxidative stress and arresting the cell cycle in g0 g1 phase
topic Candida glabrata
Human β-defensins-1
Antimicrobial peptides
Cell cycle arrest
Antioxidant enzymes
url http://www.sciencedirect.com/science/article/pii/S0753332222009581
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