scholarly journals Extending the proteomic characterization of Candida albicans exposed to stress and apoptotic inducers through data-independent acquisition mass espectrometry

2021 ◽  
Vol 3 (12) ◽  
Author(s):  
Ahinara Amador-García ◽  
Johan Malmström ◽  
Lucia Monteoliva ◽  
Concha Gil
Keyword(s):  
Oxidative Stress ◽  
Protein Folding ◽  
Candida Albicans ◽  
Stress Response ◽  
Oxidative Stress Response ◽  
Antifungal Drugs ◽  
Proteasome Activity ◽  
Main Role ◽  
Data Independent Acquisition ◽  
Almost All

Candida albicans is a commensal fungus that causes systemic infections in immunosuppressed patients. In order to deal with the changing environment during commensalism or infection, C. albicans must reprogram its proteome. Characterizing the stress-induced changes in the proteome that C. albicans uses to survive should be very useful in the development of new antifungal drugs. We studied the C. albicans global proteome after exposure to hydrogen peroxide (H2O2) and acetic acid (AA), using a DIA-MS strategy. More than 2000 C. albicans proteins were quantified using an ion library previously constructed using DDA-MS. C. albicans responded to treatment with H2O2 with an increase in the abundance of many proteins involved in the oxidative stress response, protein folding and proteasome-dependent catabolism, which led to an increased proteasome activity. The data revealed a previously unknown key role for Prn1, a protein similar to pirins, in the oxidative stress response. Treatment with AA resulted in a general decrease in the abundance of proteins involved in amino acid biosynthesis, protein folding, and rRNA processing. Almost all proteasome proteins declined, as did proteasome activity. Apoptosis was observed after treatment with H2O2, but not AA. A targeted proteomic study of 32 proteins related to apoptosis in yeast supported the results found by DIA-MS and allowed the creation of an efficient method to quantify relevant proteins after treatment with stressors (H2O2, AA, and amphotericin B). This approach also uncovered a main role for Oye32, an oxidoreductase, suggesting this protein as a possible apoptotic marker common to many stressors.

scholarly journals Extending the proteomic characterization of Candida albicans exposed to stress and apoptotic inducers through data-independent acquisition mass spectrometry

2020 ◽  
Author(s):  
Ahinara Amador-García ◽  
Inés Zapico ◽  
Johan Malmström ◽  
Lucía Monteoliva ◽  
Concha Gil
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Protein Folding ◽  
Acetic Acid ◽  
Candida Albicans ◽  
Stress Response ◽  
Amphotericin B ◽  
Drug Targets ◽  
Oxidative Stress Response ◽  
Proteasome Activity

ABSTRACTCandida albicans is a commensal fungus that causes systemic infections in immunosuppressed patients. In order to deal with the changing environment during commensalism or infection, C. albicans must reprogram its proteome. Characterizing the stress-induced changes in the proteome that C. albicans uses to survive should be very useful in the development of new antifungal drugs. We studied the C. albicans global proteome after exposure to hydrogen peroxide (H2O2) and acetic acid (AA), using a DIA-MS strategy. More than 2000 C. albicans proteins were quantified using an ion library previously constructed using DDA-MS. C. albicans responded to treatment with H2O2 with an increase in the abundance of many proteins involved in the oxidative stress response, protein folding and proteasome-dependent catabolism, which led to an increased proteasome activity. The data revealed a previously unknown key role for Prn1, a protein similar to pirins, in the oxidative stress response. Treatment with AA resulted in a general decrease in the abundance of proteins involved in amino acid biosynthesis, protein folding, and rRNA processing. Almost all proteasome proteins declined, as did proteasome activity. Apoptosis was observed after treatment with H2O2, but not AA. A targeted proteomic study of 32 proteins related to apoptosis in yeast supported the results found by DIA-MS and allowed the creation of an efficient method to quantify relevant proteins after treatment with stressors (H2O2, AA, and amphotericin B). This approach also uncovered a main role for Oye32, an oxidoreductase, suggesting this protein as a possible apoptotic marker common to many stressors.IMPORTANCEFungal infections are a worldwide health problem especially in immunocompromised patients and patients with chronic disorders. Invasive candidiasis, mainly caused by C. albicans, are among the most common fungal diseases. Despite the existence of treatments to combat candidiasis the spectra of drugs available are limited. For the discovery of new drug targets is essential to know the pathogen response to different stress conditions. Our study provides a global vision of proteomic remodeling in C. albicans after exposure to different agents such as hydrogen peroxide, acetic acid and amphotericin B that can cause apoptotic cell death. This results revealed the significance of many proteins related to oxidative stress response and proteasome activity among others. Of note, the discovery of Prn1 as a key protein in the defence against oxidative stress as well the increase in the abundance of Oye32 protein when apoptotic process occurred point out them as possible drug targets.

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 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

Roles of Cch1 and Mid1 in Morphogenesis, Oxidative Stress Response and Virulence in Candida albicans

2012 ◽  
Vol 174 (5-6) ◽  
pp. 359-369 ◽  
Author(s):  
Qilin Yu ◽  
Hui Wang ◽  
Xinxin Cheng ◽  
Ning Xu ◽  
Xiaohui Ding ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Candida Albicans ◽  
Stress Response ◽  
Oxidative Stress Response

scholarly journals Deletion of the fungus specific protein phosphatase Z1 exaggerates the oxidative stress response in Candida albicans

BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Krisztina Szabó ◽  
Ágnes Jakab ◽  
Szilárd Póliska ◽  
Katalin Petrényi ◽  
Katalin Kovács ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Candida Albicans ◽  
Stress Response ◽  
Protein Phosphatase ◽  
Transcript Level ◽  
Opportunistic Pathogen ◽  
Sublethal Concentration ◽  
Specific Protein ◽  
Oxidative Stress Response ◽  
Short Term Treatment

Abstract Background Candida albicans is an opportunistic pathogen which is responsible for widespread nosocomial infections. It encompasses a fungus specific serine/threonine protein phosphatase gene, CaPPZ1 that is involved in cation transport, cell wall integrity, oxidative stress response, morphological transition, and virulence according to the phenotypes of the cappz1 deletion mutant. Results We demonstrated that a short-term treatment with a sublethal concentration of tert-butyl hydroperoxide suppressed the growth of the fungal cells without affecting their viability, both in the cappz1 mutant and in the genetically matching QMY23 control strains. To reveal the gene expression changes behind the above observations we carried out a global transcriptome analysis. We used a pilot DNA microarray hybridization together with extensive RNA sequencing, and confirmed our results by quantitative RT-PCR. Novel functions of the CaPpz1 enzyme and oxidative stress mechanisms have been unraveled. The numbers of genes affected as well as the amplitudes of the transcript level changes indicated that the deletion of the phosphatase sensitized the response of C. albicans to oxidative stress conditions in important physiological functions like membrane transport, cell surface interactions, oxidation-reduction processes, translation and RNA metabolism. Conclusions We conclude that in the wild type C. albicans CaPPZ1 has a protective role against oxidative damage. We suggest that the specific inhibition of this phosphatase combined with mild oxidative treatment could be a feasible approach to topical antifungal therapy.

scholarly journals The Iron-Dependent Regulation of the Candida albicans Oxidative Stress Response by the CCAAT-Binding Factor

PLoS ONE ◽  
2017 ◽  
Vol 12 (1) ◽  
pp. e0170649 ◽  
Author(s):  
Ananya Chakravarti ◽  
Kyle Camp ◽  
David S. McNabb ◽  
Inés Pinto
Keyword(s):  
Oxidative Stress ◽  
Candida Albicans ◽  
Stress Response ◽  
Oxidative Stress Response ◽  
Binding Factor

scholarly journals Candida albicans-Conditioned Medium Protects Yeast Cells from Oxidative Stress: a Possible Link between Quorum Sensing and Oxidative Stress Resistance

2005 ◽  
Vol 4 (10) ◽  
pp. 1654-1661 ◽  
Author(s):  
Caroline Westwater ◽  
Edward Balish ◽  
David A. Schofield
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Candida Albicans ◽  
Stress Response ◽  
Quorum Sensing ◽  
Conditioned Medium ◽  
Oxidative Stress Response ◽  
Yeast Cells ◽  
Protective Response ◽  
Quorum Sensing Molecule

ABSTRACT Candida albicans, the most frequent fungal pathogen of humans, encounters high levels of oxidants following ingestion by professional phagocytes and through contact with hydrogen peroxide-producing bacteria. In this study, we provide evidence that C. albicans is able to coordinately regulate the oxidative stress response at the global cell population level by releasing protective molecules into the surrounding medium. We demonstrate that conditioned medium, which is defined as a filter-sterilized supernatant from a C. albicans stationary-phase culture, is able to protect yeast cells from both hydrogen peroxide and superoxide anion-generating agents. Exponential-phase yeast cells preexposed to conditioned medium were able to survive levels of oxidative stress that would normally kill actively growing yeast cells. Heat treatment, digestion with proteinase K, pH adjustment, or the addition of the oxidant scavenger alpha-tocopherol did not alter the ability of conditioned medium to induce a protective response. Farnesol, a heat-stable quorum-sensing molecule (QSM) that is insensitive to proteolytic enzymes and is unaffected by pH extremes, is partly responsible for this protective response. In contrast, the QSM tyrosol did not alter the sensitivity of C. albicans cells to oxidants. Relative reverse transcription-PCR analysis indicates that Candida-conditioned growth medium induces the expression of CAT1, SOD1, SOD2, and SOD4, suggesting that protection may be mediated through the transcriptional regulation of antioxidant-encoding genes. Together, these data suggest a link between the quorum-sensing molecule farnesol and the oxidative stress response in C. albicans.

scholarly journals Niche-Specific Activation of the Oxidative Stress Response by the Pathogenic Fungus Candida albicans

2007 ◽  
Vol 75 (5) ◽  
pp. 2143-2151 ◽  
Author(s):  
Brice Enjalbert ◽  
Donna M. MacCallum ◽  
Frank C. Odds ◽  
Alistair J. P. Brown
Keyword(s):  
Oxidative Stress ◽  
Candida Albicans ◽  
Stress Response ◽  
Fluorescent Protein ◽  
Ex Vivo ◽  
Pathogenic Fungus ◽  
Systemic Infection ◽  
Oxidative Stress Response ◽  
Mammalian Host ◽  
Phagocytic Cells

ABSTRACT Candida albicans is a major opportunistic pathogen of humans. The pathogenicity of this fungus depends upon its ability to deal effectively with the host defenses and, in particular, the oxidative burst of phagocytic cells. We have explored the activation of the oxidative stress response in C. albicans in ex vivo infection models and during systemic infection of a mammalian host. We have generated C. albicans strains that contain specific green fluorescent protein (GFP) promoter fusions and hence act as biosensors of environmental oxidative stress at the single-cell level. Having confirmed that CTA1-, TRX1-, and TTR1/GRX2-GFP reporters respond specifically to oxidative stress, and not to heat shock, nitrosative, or osmotic stresses, we used these reporters to show that individual C. albicans cells activate an oxidative stress response following phagocytosis by neutrophils, but not by macrophages. Significantly, only a small proportion of C. albicans cells (about 4%) activated an oxidative stress response during systemic infection of the mouse kidney. The response of these cells was generally equivalent to exposure to 0.4 mM hydrogen peroxide in vitro. We conclude that most C. albicans cells are exposed to an oxidative stress when they come into contact with neutrophils in the bloodstream of the host but that oxidative killing is no longer a significant threat once an infection has been established in the kidney.

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