Superoxide dismutases and glutaredoxins have a distinct role in the response of Candida albicans to oxidative stress generated by the chemical compounds menadione and diamide

The glucocorticoid betamethasone (BM) has potent anti-inflammatory and immunosuppressive effects; however, it increases the susceptibility of patients to superficial Candida infections. Previously we found that this disadvantageous side effect can be counteracted by menadione sodium bisulfite (MSB) induced oxidative stress treatment. The fungus specific protein phosphatase Z1 (CaPpz1) has a pivotal role in oxidative stress response of Candida albicans and was proposed as a potential antifungal drug target. The aim of this study was to investigate the combined effects of CaPPZ1 gene deletion and MSB treatment in BM pre-treated C. albicans cultures. We found that the combined treatment increased redox imbalance, enhanced the specific activities of antioxidant enzymes, and reduced the growth in cappz1 mutant (KO) strain. RNASeq data demonstrated that the presence of BM markedly elevated the number of differentially expressed genes in the MSB treated KO cultures. Accumulation of reactive oxygen species, increased iron content and fatty acid oxidation, as well as the inhibiting ergosterol biosynthesis and RNA metabolic processes explain, at least in part, the fungistatic effect caused by the combined stress exposure. We suggest that the synergism between MSB treatment and CaPpz1 inhibition could be considered in developing of a novel combinatorial antifungal strategy accompanying steroid therapy.

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Linalool-induced oxidative stress processes in the human pathogen Candida albicans

Acta Biologica Hungarica ◽

10.1556/018.68.2017.2.9 ◽

2017 ◽

Vol 68 (2) ◽

pp. 220-231 ◽

Cited By ~ 3

Author(s):

Gábor Máté ◽

Dominika Kovács ◽

Zoltán Gazdag ◽

Miklós Pesti ◽

Árpád Szántó

Keyword(s):

Oxidative Stress ◽

Candida Albicans ◽

Human Pathogen ◽

Human Pathogen Candida Albicans

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Oxidative Stress in Candida albicans Infection

Oxidative Stress in Microbial Diseases ◽

10.1007/978-981-13-8763-0_21 ◽

2019 ◽

pp. 379-393

Author(s):

Santanu Palchaudhuri ◽

Dhrubajyoti Chattopadhyay

Keyword(s):

Oxidative Stress ◽

Candida Albicans ◽

Candida Albicans Infection

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Potentiation of Antibiofilm Activity of Amphotericin B by Superoxide Dismutase Inhibition

Oxidative Medicine and Cellular Longevity ◽

10.1155/2013/704654 ◽

2013 ◽

Vol 2013 ◽

pp. 1-7 ◽

Cited By ~ 12

Author(s):

Katrijn De Brucker ◽

Anna Bink ◽

Els Meert ◽

Bruno P. A. Cammue ◽

Karin Thevissen

Keyword(s):

Reactive Oxygen Species ◽

Superoxide Dismutase ◽

Candida Albicans ◽

Amphotericin B ◽

Reactive Oxygen ◽

Intracellular Reactive Oxygen Species ◽

Superoxide Dismutases ◽

Antibiofilm Activity ◽

Oxygen Species ◽

Ammonium Tetrathiomolybdate

This study demonstrates a role for superoxide dismutases (Sods) in governing tolerance ofCandida albicansbiofilms to amphotericin B (AmB). Coincubation ofC. albicansbiofilms with AmB and the Sod inhibitors N,N′-diethyldithiocarbamate (DDC) or ammonium tetrathiomolybdate (ATM) resulted in reduced viable biofilm cells and increased intracellular reactive oxygen species levels as compared to incubation of biofilm cells with AmB, DDC, or ATM alone. Hence, Sod inhibitors can be used to potentiate the activity of AmB againstC. albicansbiofilms.

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Superoxide Dismutases (SODs) and Their Role in Regulating Abiotic Stress induced Oxidative Stress in Plants

Reactive Oxygen, Nitrogen and Sulfur Species in Plants ◽

10.1002/9781119468677.ch3 ◽

2019 ◽

pp. 53-88 ◽

Cited By ~ 1

Author(s):

Panchanand Mishra ◽

Pallavi Sharma

Keyword(s):

Oxidative Stress ◽

Abiotic Stress ◽

Superoxide Dismutases

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Oxidative stress induced by piperine leads to apoptosis in Candida albicans

Medical Mycology ◽

10.1093/mmy/myaa058 ◽

2020 ◽

Author(s):

Archana Thakre ◽

Vyankatesh Jadhav ◽

Rubina Kazi ◽

Amruta Shelar ◽

Rajendra Patil ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Cycle ◽

Candida Albicans ◽

Cell Cycle Arrest ◽

Resistant Strain ◽

Membrane Integrity ◽

Synergistic Activity ◽

Biofilm Growth ◽

Cycle Arrest ◽

Apoptosis Assay

Abstract Candida albicans is a member of pathogens with potential drug resistance threat that needs novel chemotherapeutic strategies. Considering the multifarious biological activities including bioenhancer activity, anti-Candida potential of piperine was evaluated against planktonic/biofilm and hyphal growth of C. albicans alone or in combination as a synergistic agent with fluconazole. Piperine inhibits planktonic growth at or less than 15 μg/ml, hyphae induction at 5 μg/ml concentration, and exhibits stage-dependent activity against biofilm growth of a fluconazole-resistant strain of C. albicans (ATCC10231). Though piperine couldn't kill inoculum completely at minimum inhibitory concentration (MIC), it is fungicidal at higher concentrations, as shown in apoptosis assay. FIC index values indicate that piperine exhibits excellent synergistic activity with fluconazole against planktonic (0.123) and biofilm (0.215) growth of an FLC resistant strain. Mode of anti-Candida activity was studied by identifying piperine responsive proteins wherein the abundance of 25 proteins involved in stress response, signal transduction and cell cycle were modulated (22 up and 3 down-regulated) significantly in response to piperine (MIC50). Modulation of the proteins involved suggests that piperine affects membrane integrity leading to oxidative stress followed by cell cycle arrest and apoptosis in C. albicans. Flow cytometry-based mitochondrial membrane potential (MMP), cell cycle and apoptosis assay, as well as real-time quantitative polymerase chain reaction analysis of selected genes, confirms piperine induced oxidative stress (TRR1), cell cycle arrest and apoptosis (CaMCA1). Based on our results, we conclude that piperine inhibits planktonic and difficult-to treat-biofilm growth of C. albicans by affecting membrane integrity thereby inducing oxidative stress and apoptosis. Lay Abstract Piperine inhibit Candida albicans growth (planktonic and biofilm) significantly in our study. Piperine exhibits excellent synergistic potential with fluconazole The proteome analysis suggests that piperine induced membrane damage leads to oxidative stress followed by cell cycle arrest and apoptosis.

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