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.

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 High Resistance to Oxidative Stress in the Fungal Pathogen Candida glabrata Is Mediated by a Single Catalase, Cta1p, and Is Controlled by the Transcription Factors Yap1p, Skn7p, Msn2p, and Msn4p

2008 ◽  
Vol 7 (5) ◽  
pp. 814-825 ◽  
Author(s):  
Mayra Cuéllar-Cruz ◽  
Marcela Briones-Martin-del-Campo ◽  
Israel Cañas-Villamar ◽  
Javier Montalvo-Arredondo ◽  
Lina Riego-Ruiz ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Saccharomyces Cerevisiae ◽  
Candida Albicans ◽  
Transcription Factors ◽  
Adaptive Response ◽  
Fungal Pathogen ◽  
Candida Glabrata ◽  
Systemic Infection ◽  
Oxidative Stress Response

ABSTRACT We characterized the oxidative stress response of Candida glabrata to better understand the virulence of this fungal pathogen. C. glabrata could withstand higher concentrations of H2O2 than Saccharomyces cerevisiae and even Candida albicans. Stationary-phase cells were extremely resistant to oxidative stress, and this resistance was dependent on the concerted roles of stress-related transcription factors Yap1p, Skn7p, and Msn4p. We showed that growing cells of C. glabrata were able to adapt to high levels of H2O2 and that this adaptive response was dependent on Yap1p and Skn7p and partially on the general stress transcription factors Msn2p and Msn4p. C. glabrata has a single catalase gene, CTA1, which was absolutely required for resistance to H2O2 in vitro. However, in a mouse model of systemic infection, a strain lacking CTA1 showed no effect on virulence.

scholarly journals Discovery of a Highly Selective MC1R Agonists Pentapeptide to Be Used as a Skin Pigmentation Enhancer and with Potential Anti-Aging Properties

2019 ◽  
Vol 20 (24) ◽  
pp. 6143 ◽  
Author(s):  
Eileen Jackson ◽  
Marc Heidl ◽  
Dominik Imfeld ◽  
Laurent Meeus ◽  
Rolf Schuetz ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Defense Mechanisms ◽  
Ex Vivo ◽  
Skin Pigmentation ◽  
Oxidative Stress Response ◽  
Melanocortin 1 Receptor ◽  
Melanocyte Stimulating Hormone ◽  
Uva Irradiation

One of the first lines of cutaneous defense against photoaging is (a) the synthesis of melanin and (b) the initiation of an oxidative stress response to protect skin against the harmful effects of solar radiation. Safe and selective means to stimulate epidermal pigmentation associated with oxidative stress defense are; however, scarce. Activation of the melanocortin-1 receptor (MC1R) on epidermal melanocytes represents a key step in cutaneous pigmentation initiation and, additionally, it regulates cellular defense mechanisms like oxidative stress and DNA-repair. Thus, making the activation of MC1R an attractive strategy for modulating skin pigmentation and oxidative stress. In this context, we designed and synthesized pentapeptides that act as MC1R agonists. These peptides bound, with high potency, to MC1R and activated cAMP synthesis in CHO cells expressing human MC1R. Using one lead pentapeptide, we could show that this activation of MC1R was specific as testing the activation of other G-protein coupled receptors, including the MC-receptor family, was negative. In vitro efficacy on mouse melanoma cells showed similar potency as for the synthetic MC1R agonist alpha-melanocyte stimulating hormone (NDP-alpha-MSH). Moreover, we could reproduce this activity in human skin tissue culture. The lead pentapeptide was able to induce ex-vivo protein expression of key melanogenesis markers melanocyte inducing transcription factor (MITF), tyrosinase (TYR), and tyrosinase-related protein 1 (TYRP-1). Concerning oxidative stress response, we found that the pentapeptide enhanced the activation of Nrf2 after UVA-irradiation. Our results make this pentapeptide an ideal candidate as a skin pigmentation enhancer that mimics alpha-MSH and may also have anti-photoaging effects on the skin.

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 Translational Regulation Promotes Oxidative Stress Resistance in the Human Fungal Pathogen Cryptococcus neoformans

2019 ◽  
Author(s):  
Jay Leipheimer ◽  
Amanda L. M. Bloom ◽  
Christopher S. Campomizzi ◽  
Yana Salei ◽  
John C. Panepinto
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Cryptococcus Neoformans ◽  
Stress Responses ◽  
Carbon Starvation ◽  
Oxidative Stress Response ◽  
Initiation Factor ◽  
Mammalian Host ◽  
Cellular Stresses ◽  
Translational Suppression

AbstractCryptococcus neoformans is one of the few environmental fungi that can survive within a mammalian host and cause disease. Although many of the factors responsible for establishing virulence have been recognized, how they are expressed in response to certain host derived cellular stresses is rarely addressed. Here we characterize the temporal translational response of C. neoformans to oxidative stress. We find that translation is largely inhibited through the phosphorylation of the critical initiation factor elF2α by a sole kinase. Preventing elF2α mediated translational suppression resulted in growth sensitivity to hydrogen peroxide (H2O2). Our work suggests that translational repression in response to H2O2 partly facilitates oxidative stress adaptation by accelerating the decay of abundant non-stress related transcripts while facilitating the proper expression of critical oxidative stress response factors. Carbon starvation, which seems to induce translational suppression that is independent elF2α, partly restored transcript decay and the expression of the critical oxidative stress response transcript Thioredoxin Reductase 1 (TRR1). Our results illustrate translational suppression as a key determinant of select mRNA decay, gene expression, and subsequent survival in response to oxidative stress.ImportanceFungal survival in a mammalian host requires the coordinated expression and downregulation of a large cohort of genes in response to cellular stresses. Initial infection with C. neoformans occurs at the lungs, where it interacts with host macrophages. Surviving macrophage derived cellular stresses, such as the production of reactive oxygen and nitrogen species, is believed to promote dissemination into the central nervous system. Therefore, investigating how an oxidative stress resistant phenotype is brought about in C. neoformans furthers our understanding of not only fungal pathogenesis but also unveils mechanisms of stress induced gene reprogramming. We discovered that H2O2 derived oxidative stress resulted in severe translational suppression and that this suppression was necessary for the accelerated decay and expression of tested transcripts. Surprisingly, compounding oxidative stress with carbon starvation resulted in a decrease in peroxide mediated killing, revealing unexpected synergy between stress responses.

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