ATP1 promotes Candida albicans to escape from macrophage killing through regulating oxidative stress

2020 ◽  
Keyword(s):  
Oxidative Stress ◽  
Candida Albicans ◽  
Macrophage Killing

scholarly journals The Transcription Factor Sfp1 Regulates the Oxidative Stress Response in Candida albicans

2019 ◽  
Vol 7 (5) ◽  
pp. 131 ◽  
Author(s):  
Shao-Yu Lee ◽  
Hsueh-Fen Chen ◽  
Ying-Chieh Yeh ◽  
Yao-Peng Xue ◽  
Chung-Yu Lan
Keyword(s):  
Oxidative Stress ◽  
Transcription Factor ◽  
Candida Albicans ◽  
Stress Response ◽  
Oxidative Stress Response ◽  
Antifungal Drugs ◽  
Wild Type ◽  
Antioxidant Genes ◽  
Type C ◽  
Macrophage Killing

Candida albicans is a commensal that inhabits the skin and mucous membranes of humans. Because of the increasing immunocompromised population and the limited classes of antifungal drugs available, C. albicans has emerged as an important opportunistic pathogen with high mortality rates. During infection and therapy, C. albicans frequently encounters immune cells and antifungal drugs, many of which exert their antimicrobial activity by inducing the production of reactive oxygen species (ROS). Therefore, antioxidative capacity is important for the survival and pathogenesis of C. albicans. In this study, we characterized the roles of the zinc finger transcription factor Sfp1 in the oxidative stress response against C. albicans. A sfp1-deleted mutant was more resistant to oxidants and macrophage killing than wild-type C. albicans and processed an active oxidative stress response with the phosphorylation of the mitogen-activated protein kinase (MAPK) Hog1 and high CAP1 expression. Moreover, the sfp1-deleted mutant exhibited high expression levels of antioxidant genes in response to oxidative stress, resulting in a higher total antioxidant capacity, glutathione content, and glutathione peroxidase and superoxide dismutase enzyme activity than the wild-type C. albicans. Finally, the sfp1-deleted mutant was resistant to macrophage killing and ROS-generating antifungal drugs. Together, our findings provide a new understanding of the complex regulatory machinery in the C. albicans oxidative stress response.

scholarly journals The Negative Effect of Protein Phosphatase Z1 Deletion on the Oxidative Stress Tolerance of Candida albicans Is Synergistic with Betamethasone Exposure

2021 ◽  
Vol 7 (7) ◽  
pp. 540
Author(s):  
Ágnes Jakab ◽  
Tamás Emri ◽  
Kinga Csillag ◽  
Anita Szabó ◽  
Fruzsina Nagy ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Candida Albicans ◽  
Protein Phosphatase ◽  
Combined Treatment ◽  
Specific Protein ◽  
Ergosterol Biosynthesis ◽  
Acid Oxidation ◽  
Menadione Sodium Bisulfite ◽  
Rnaseq Data ◽  
Negative Effect

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.

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

2017 ◽  
Vol 68 (2) ◽  
pp. 220-231 ◽  
Author(s):  
Gábor Máté ◽  
Dominika Kovács ◽  
Zoltán Gazdag ◽  
Miklós Pesti ◽  
Árpád Szántó
Keyword(s):  
Oxidative Stress ◽  
Candida Albicans ◽  
Human Pathogen ◽  
Human Pathogen Candida Albicans

Oxidative stress induced by piperine leads to apoptosis in Candida albicans

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.

scholarly journals Trehalose accumulation induced during the oxidative stress response is independent of TPS1 mRNA levels in Candida albicans

2003 ◽  
Vol 6 (2) ◽  
pp. 121-125 ◽  
Author(s):  
�scar Zaragoza ◽  
Pilar Gonz�lez-P�rraga ◽  
Yolanda Pedre�o ◽  
Francisco J. Alvarez-Peral ◽  
Juan-Carlos Arg�elles
Keyword(s):  
Oxidative Stress ◽  
Candida Albicans ◽  
Stress Response ◽  
Oxidative Stress Response ◽  
Mrna Levels ◽  
Trehalose Accumulation

scholarly journals Identification and Characterization of Cor33p, a Novel Protein Implicated in Tolerance towards Oxidative Stress in Candida albicans

2005 ◽  
Vol 4 (12) ◽  
pp. 2160-2169 ◽  
Author(s):  
K. Sohn ◽  
M. Roehm ◽  
C. Urban ◽  
N. Saunders ◽  
D. Rothenstein ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Candida Albicans ◽  
Wild Type ◽  
Two Dimensional Gel Electrophoresis ◽  
Functional Link ◽  
Yeast Peptone Dextrose ◽  
Downstream Effectors ◽  
Benzylic Ether

ABSTRACT We applied two-dimensional gel electrophoresis to identify downstream effectors of CPH1 and EFG1 under hypha-inducing conditions in Candida albicans. Among the proteins that were expressed in wild-type cells but were strongly downregulated in a cph1Δ/efg1Δ double mutant in α-minimal essential medium at 37°C, we could identify not-yet-characterized proteins, including Cor33-1p and Cor33-2p. The two proteins are almost identical (97% identity) and represent products of allelic isoforms of the same gene. Cor33p is highly similar to Cip1p from Candida sp. but lacks any significant homology to proteins from Saccharomyces cerevisiae. Strikingly, both proteins share homology with phenylcoumaran benzylic ether reductases and isoflavone reductases from plants. For other hypha-inducing media, like yeast-peptone-dextrose (YPD) plus serum at 37°C, we could not detect any transcription for COR33 in wild-type cells, indicating that Cor33p is not hypha specific. In contrast, we found a strong induction for COR33 when cells were treated with 5 mM hydrogen peroxide. However, under oxidative conditions, transcription of COR33 was not dependent on EFG1, indicating that other regulatory factors are involved. In fact, upregulation depends on CAP1 at least, as transcript levels were clearly reduced in a Δcap1 mutant strain under oxidative conditions. Unlike in wild-type cells, transcription of COR33 in a tsa1Δ mutant can be induced by treatment with 0.1 mM hydrogen peroxide. This suggests a functional link between COR33 and thiol-specific antioxidant-like proteins that are important in the oxidative-stress response in yeasts. Concordantly, cor33Δ deletion mutants show retarded growth on YPD plates supplemented with hydrogen peroxide, indicating that COR33 in general is implicated in conferring tolerance toward oxidative stress on Candida albicans.

scholarly journals Effects of [Cu(2-MeSNic)2(MeNia)2(H2O)2]·H2O and [Cu(2-MeSNic)2(H2O)]2 on Candida albicans

2015 ◽  
Vol 8 (1) ◽  
pp. 39-43
Author(s):  
Barbora Kaliňáková ◽  
Daniela Hudecová ◽  
Peter Segľa ◽  
Martina Palicová ◽  
Jozef Švorec
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Candida Albicans ◽  
Copper Complexes ◽  
Membrane Damage ◽  
Thiobarbituric Acid ◽  
Intracellular Reactive Oxygen Species ◽  
Oxygen Species ◽  
Thiobarbituric Acid Reactive Substances ◽  
Hoechst 33342

Abstract Probable mode of action of new copper complexes of 2-methylthionicotinate (2-MeSNic) of composition [Cu(2-MeSNic)2(H2O)2] and [Cu(2-MeSNic)2(MeNia)2(H2O)2]·H2O (where MeNia is N-methylnicotinamide) is described. Both partial growth inhibition of Candida albicans (IC50 ≥ 1.78 mmol·L−1, MIC ≥ 2.5 mmol·L−1) and leak of proteins into the extracellular space (more than 80 %) were observed in the presence of these copper complexes. The membrane damage was detected by staining with Hoechst 33342, propidium iodide and methylene blue. Ascorbic acid potentiated antifungal activity of copper complexes approximately seven-fold and induced the oxidative stress, respectively. The production of intracellular reactive oxygen species was visualized by dichlorofluorescein. Thiobarbituric acid-reactive substances were formed as a by-product of lipid peroxidation.

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