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

Cuéllar‐Cruz, Mayra; Briones-Martin-del-Campo, Marcela; Cañas-Villamar, Israel; Montalvo-Arredondo, Javier; Castaño, Irene; Peñas, Alejandro De Las

doi:10.1128/ec.00011-08

Cited by 149 publications

(146 citation statements)

References 77 publications

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“…This rescue of the virulence phenotype has been observed for another C. glabrata mutant we have identified (A. Taravaud, J. Bourdeaux, and D. Ferrandon, unpublished observations). It will be interesting to determine whether the C. glabrata catalase is required for the pathogen to withstand the cellular immune response, because it is currently unknown whether Drosophila hemocytes produce an oxidative shock to kill ingested microbes (56). The existence of an oxidative burst can also be tested on the host side by reducing genetically the expression of the Dual oxidase gene or that of the NADPH oxidase gene in hemocytes.…”

Section: Glabrata Persist Even In Wild-type Fliesmentioning

confidence: 99%

The Drosophila Toll Pathway Controls but Does Not Clear Candida glabrata Infections

Quintin

Asmar

Matskevich

et al. 2013

The Journal of Immunology

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The pathogenicity of Candida glabrata to patients remains poorly understood for lack of convenient animal models to screen large numbers of mutants for altered virulence. In this study, we explore the minihost model Drosophila melanogaster from the dual perspective of host and pathogen. As in vertebrates, wild-type flies contain C. glabrata systemic infections yet are unable to kill the injected yeasts. As for other fungal infections in Drosophila, the Toll pathway restrains C. glabrata proliferation. Persistent C. glabrata yeasts in wild-type flies do not appear to be able to take shelter in hemocytes from the action of the Toll pathway, the effectors of which remain to be identified. Toll pathway mutant flies succumb to injected C. glabrata. In this immunosuppressed background, cellular defenses provide a residual level of protection. Although both the Gram-negative binding protein 3 pattern recognition receptor and the Persephone protease-dependent detection pathway are required for Toll pathway activation by C. glabrata, only GNBP3, and not psh mutants, are susceptible to the infection. Both Candida albicans and C. glabrata are restrained by the Toll pathway, yet the comparative study of phenoloxidase activation reveals a differential activity of the Toll pathway against these two fungal pathogens. Finally, we establish that the high-osmolarity glycerol pathway and yapsins are required for virulence of C. glabrata in this model. Unexpectedly, yapsins do not appear to be required to counteract the cellular immune response but are needed for the colonization of the wild-type host.

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Section: Glabrata Persist Even In Wild-type Fliesmentioning

confidence: 99%

The Drosophila Toll Pathway Controls but Does Not Clear Candida glabrata Infections

Quintin

Asmar

Matskevich

et al. 2013

The Journal of Immunology

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“…Accordingly, an inactivation of these detoxifying enzymes leads to severe loss in virulence and viability inside immune cells (59). The oxidative stress response of C. glabrata is controlled by the transcription factors Yap1, Skn7, Msn2, and Msn4 (30,60,61), which mediate resistance of C. glabrata to H 2 O 2 and other oxidants. Additionally, C. glabrata possesses a catalase (Cta1p) that is required to survive oxidative stress (although this is dispensable in a mouse model of systemic infection) (60,62).…”

Section: Glabrata Cells Repress the Production Of High Ros Levelsmentioning

confidence: 99%

“…The oxidative stress response of C. glabrata is controlled by the transcription factors Yap1, Skn7, Msn2, and Msn4 (30,60,61), which mediate resistance of C. glabrata to H 2 O 2 and other oxidants. Additionally, C. glabrata possesses a catalase (Cta1p) that is required to survive oxidative stress (although this is dispensable in a mouse model of systemic infection) (60,62). In agreement with a previous study, which showed that C. glabrata can suppress the release of oxidants during its interaction with a murine macrophage cell line (21), in this study we demonstrate repression of ROS production by primary human macrophages.…”

Section: Glabrata Cells Repress the Production Of High Ros Levelsmentioning

confidence: 99%

The Facultative Intracellular Pathogen Candida glabrata Subverts Macrophage Cytokine Production and Phagolysosome Maturation

Seider

Brunke

Schild

et al. 2011

The Journal of Immunology

184

226

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Although Candida glabrata is an important human pathogenic yeast, its pathogenicity mechanisms are largely unknown. Immune evasion strategies seem to play key roles during infection, since very little inflammation is observed in mouse models. Furthermore, C. glabrata multiplies intracellularly after engulfment by macrophages. In this study, we sought to identify the strategies that enable C. glabrata to survive phagosome biogenesis and antimicrobial activities within human monocyte-derived macrophages. We show that, despite significant intracellular proliferation, macrophage damage or apoptosis was not apparent, and production of reactive oxygen species was inhibited. Additionally, with the exception of GM-CSF, levels of pro- and anti-inflammatory cytokines were only marginally increased. We demonstrate that adhesion to and internalization by macrophages occur within minutes, and recruitment of endosomal early endosomal Ag 1 and lysosomal-associated membrane protein 1 indicates phagosome maturation. However, phagosomes containing viable C. glabrata, but not heat-killed yeasts, failed to recruit cathepsin D and were only weakly acidified. This inhibition of acidification did not require fungal viability, but it had a heat-sensitive surface attribute. Therefore, C. glabrata modifies the phagosome into a nonacidified environment and multiplies until the host cells finally lyse and release the fungi. Our results suggest persistence of C. glabrata within macrophages as a possible immune evasion strategy.

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“…exhibit unequal oxidative stress resistances in vitro [20][21][22] , and different in vitro virulence potentials 23 , and we proposed that this may contribute to the capacity of each species to cause candidemia 22 . Taking into account these differences, total glutathione levels and the cellular TAC were assessed in 8 Candida species.…”

Section: Introductionmentioning

confidence: 99%

Glutathione levels in and total antioxidant capacity of Candida sp. cells exposed to oxidative stress caused by hydrogen peroxide

Abegg

Alabarse

Schüller

et al. 2012

Rev. Soc. Bras. Med. Trop.

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Candida albicans, C. glabrata, C. tropicalis, and C. parapsilosis account for approximately 95% of identifiable Candida infections. Other species, including C. krusei, C. lusitaniae, and C. guilliermondii, account for less than 5% of cases of invasive candidiasis. The most common causative agent is still C. albicans, but its incidence is declining and the frequencies of other species are increasing. Recently, Furlaneto et al. 1 noted that non-albicans Candida was the predominant species in different clinical specimens, with the exception of urine samples, in a Brazilian tertiary-care hospital. Invasive candidiasis has a mortality rate that approaches 40% 2,3 . Although most people are colonized by Candida sp., the majority never develop invasive candidiasis. Alterations in host immunity, physiological features, or normal microflora, rather than the acquisition of novel or hypervirulent factors by Candida, are suggested to degenerate the commensal-host interaction and lead to an opportunistic infection 4 .During the course of a systemic infection, Candida cells are engulfed by host phagocytes, where they are exposed to reactive oxygen species (ROS) 5 . ROS contribute to the killing of C. albicans in both cultured cells and entire organisms [6][7][8][9] . Upon incubation with macrophages, C. albicans deoxyribonucleic acid (DNA) repair genes are transcriptionally induced, suggesting that DNA damage indeed occurs in the phagosome and that genotoxic hypersensitivity stress would be disadvantageous to the pathogen 10 . Recently, it was demonstrated that a large proportion of C. albicans cell surface antigens related to acute candidemia are involved in oxidative stress 4 . In C. albicans, hyphal cells ABSTRACT Introduction: The capacity to overcome the oxidative stress imposed by phagocytes seems to be critical for Candida species to cause invasive candidiasis. Methods: To better characterize the oxidative stress response (OSR) of 8 clinically relevant Candida sp., glutathione, a vital component of the intracellular redox balance, was measured using the 5,5'-dithiobis-(2-nitrobenzoic acid (DTNB)-glutathione disulfide (GSSG) reductase reconversion method; the total antioxidant capacity (TAC) was measured using a modified method based on the decolorization of the 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic) acid radical cation (ABTS* + ). Both methods were used with cellular Candida sp. extracts treated or not with hydrogen peroxide (0.5 mM). Results: Oxidative stress induced by hydrogen peroxide clearly reduced intracellular glutathione levels. This depletion was stronger in Candida albicans and the levels of glutathione in untreated cells were also higher in this species. The TAC demonstrated intra-specific variation. Conclusions: Glutathione levels did not correlate with the measured TAC values, despite this being the most important non-enzymatic intracellular antioxidant molecule. The results indicate that the isolated measurement of TAC does not give a clear picture of the ability of a given Candida sp. to resp...

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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

Cited by 149 publications

References 77 publications

The Drosophila Toll Pathway Controls but Does Not Clear Candida glabrata Infections

The Drosophila Toll Pathway Controls but Does Not Clear Candida glabrata Infections

The Facultative Intracellular Pathogen Candida glabrata Subverts Macrophage Cytokine Production and Phagolysosome Maturation

Glutathione levels in and total antioxidant capacity of Candida sp. cells exposed to oxidative stress caused by hydrogen peroxide

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