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.

The oxidative stress response of the opportunistic fungal pathogen Candida glabrata

2014 ◽  
Vol 31 (1) ◽  
pp. 67-71 ◽  
Author(s):  
Marcela Briones-Martin-Del-Campo ◽  
Emmanuel Orta-Zavalza ◽  
Jacqueline Juarez-Cepeda ◽  
Guadalupe Gutierrez-Escobedo ◽  
Israel Cañas-Villamar ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Fungal Pathogen ◽  
Candida Glabrata ◽  
Oxidative Stress Response ◽  
Opportunistic Fungal Pathogen

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 Association of the Skn7 and Yap1 Transcription Factors in the Saccharomyces cerevisiae Oxidative Stress Response

2011 ◽  
Vol 10 (6) ◽  
pp. 761-769 ◽  
Author(s):  
K. E. Mulford ◽  
J. S. Fassler
Keyword(s):  
Oxidative Stress ◽  
Saccharomyces Cerevisiae ◽  
Transcription Factors ◽  
Stress Response ◽  
Wall Stress ◽  
Oxidative Stress Response ◽  
Independent Manner ◽  
Content Type ◽  
Stress Response Genes ◽  
Two Factors

ABSTRACT Saccharomyces cerevisiae Skn7p is a stress response transcription factor that undergoes aspartyl phosphorylation by the Sln1p histidine kinase. Aspartyl phosphorylation of Skn7p is required for activation of genes required in response to wall stress, but Skn7p also activates oxidative stress response genes in an aspartyl phosphorylation-independent manner. The presence of binding sites for the Yap1p and Skn7p transcription factors in oxidative stress response promoters and the oxidative stress-sensitive phenotypes of SKN7 and YAP1 mutants suggest that these two factors work together. We present here evidence for a DNA-independent interaction between the Skn7 and Yap1 proteins that involves the receiver domain of Skn7p and the cysteine-rich domains of Yap1p. The interaction with Yap1p may help partition the Skn7 protein to oxidative stress response promoters when the Yap1 protein accumulates in the nucleus.

The Pbs2 MAP kinase kinase is essential for the oxidative-stress response in the fungal pathogen Candida albicans

Microbiology ◽  
2005 ◽  
Vol 151 (4) ◽  
pp. 1033-1049 ◽  
Author(s):  
David M. Arana ◽  
César Nombela ◽  
Rebeca Alonso-Monge ◽  
Jesús Pla
Keyword(s):  
Oxidative Stress ◽  
Candida Albicans ◽  
Stress Response ◽  
Map Kinase ◽  
Fungal Pathogen ◽  
Oxidative Stress Response ◽  
Map Kinase Kinase

scholarly journals Trans-cellular tunnels induced by the fungal pathogen Candida albicans facilitate invasion through successive epithelial cells without host damage

2021 ◽  
Author(s):  
Joy Lachat ◽  
Alice Pascault ◽  
Delphine Thibaut ◽  
Rémi Le Borgne ◽  
Jean-Marc Verbavatz ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Fungal Pathogen ◽  
Single Cell Analysis ◽  
Three Dimensional ◽  
Systemic Infection ◽  
Host Cells ◽  
Galectin 3 ◽  
Opportunistic Fungal Pathogen ◽  
Epithelial Layers

SummaryThe opportunistic fungal pathogen Candida albicans is normally commensal, residing in the mucosa of most healthy individuals. In susceptible hosts, its filamentous hyphal form can invade epithelial layers leading to superficial or severe systemic infection. Invasion is mainly intracellular, though it causes no apparent damage to host cells. We investigated the invasive lifestyle of C. albicans in vitro using live-cell imaging and the damage-sensitive reporter galectin-3. Quantitative single cell analysis showed that invasion can result in host membrane breaching at different stages of invasion and cell death, or in traversal of host cells without membrane breaching. Membrane labelling and three-dimensional “volume” electron microscopy revealed that hyphae can traverse several host cells within trans-cellular tunnels that are progressively remodelled and may undergo ‘inflations’ linked to host glycogen stores, possibly during nutrient uptake. Thus, C. albicans invade epithelial tissues by either inflicting or avoiding host damage, the latter facilitated by trans-cellular tunnelling.

Role of glutathione in the oxidative stress response in the fungal pathogen Candida glabrata

2013 ◽  
Vol 59 (3) ◽  
pp. 91-106 ◽  
Author(s):  
Guadalupe Gutiérrez-Escobedo ◽  
Emmanuel Orta-Zavalza ◽  
Irene Castaño ◽  
Alejandro De Las Peñas
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Fungal Pathogen ◽  
Candida Glabrata ◽  
Oxidative Stress Response

scholarly journals The Siderophore Iron Transporter of Candida albicans (Sit1p/Arn1p) Mediates Uptake of Ferrichrome-Type Siderophores and Is Required for Epithelial Invasion

2002 ◽  
Vol 70 (9) ◽  
pp. 5246-5255 ◽  
Author(s):  
Petra Heymann ◽  
Michaela Gerads ◽  
Martin Schaller ◽  
Francoise Dromer ◽  
Günther Winkelmann ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Candida Albicans ◽  
Fungal Pathogen ◽  
Systemic Infection ◽  
Specific Process ◽  
Human Fungal Pathogen ◽  
Iron Salts ◽  
Mutant Strains ◽  
Epithelial Invasion ◽  
Triacetylfusarinine C

ABSTRACT The human fungal pathogen Candida albicans contains a close homologue of yeast siderophore transporters, designated Sit1p/Arn1p. We have characterized the function of SIT1 in C. albicans by constructing sit1 deletion strains and testing their virulence and ability to utilize a range of siderophores and other iron complexes. sit1 mutant strains are defective in the uptake of ferrichrome-type siderophores including ferricrocin, ferrichrysin, ferrirubin, coprogen, and triacetylfusarinine C. A mutation of FTR1 did not impair the use of these siderophores but did affect the uptake of ferrioxamines E and B, as well as of ferric citrate, indicating that their utilization was independent of Sit1p. Hemin was a source of iron for both sit1 and ftr1 mutants, suggesting a pathway of hemin uptake distinct from that of siderophores and iron salts. Heterologous expression of SIT1 in the yeast Saccharomyces cerevisiae confirmed the function of Sit1p as a transporter for ferrichrome-type siderophores. The sit1 mutant was defective in infection of a reconstituted human epithelium as a model for human oral mucosa, while the SIT1 strain was invasive. In contrast, both sit1 and SIT1 strains were equally virulent in the mouse model of systemic infection. These results suggest that siderophore uptake by Sit1p/Arn1p is required in a specific process of C. albicans infection, namely epithelial invasion and penetration, while in the blood or within organs other sources of iron, including heme, may be used.

scholarly journals Systematic Identification and Characterization of Five Transcription Factors Mediating the Oxidative Stress Response in Candida Albicans

2020 ◽  
Author(s):  
YingChao Cui ◽  
DaoSheng Wang ◽  
Clarissa J. Nobile ◽  
Danfeng Dong ◽  
Qi Ni ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Transcription Factor ◽  
Candida Albicans ◽  
Transcription Factors ◽  
Stress Response ◽  
Oxidative Stress Response ◽  
Functional Enrichment ◽  
Fungal Virulence ◽  
Potent Inducer ◽  
Mutant Strains

Abstract BackgroundCandida albicans is an opportunistic human fungal pathogen that can cause both superficial and systemic infections, especially in immunocompromised individuals. In response to C. albicans infections, innate immune cells of the host produce and accumulate reactive oxygen species (ROS) that can lead to irreversible damage and apoptosis of fungal cells. Prior studies have identified several transcription factors involved in the oxidative stress response of C. albicans. However, a systematic study to identify transcription factors mediating the oxidative response had not been previously conducted. ResultsIn this study, we screened a comprehensive transcription factor mutant library consisting of 211 transcription factor deletion mutant strains in the presence and absence of H2O2, a potent inducer of ROS, and identified five transcription factors (Skn7, Dpb4, Cap1, Dal81 and Stp2) involved in the response to H2O2. Genome-wide transcriptional profiling revealed that H2O2 induced a discreet set of genes differentially regulated in common among the five transcription factor mutant strains identified. Functional enrichment analysis identified KEGG pathways pertaining to glycolysis/gluconeogenesis, amino sugar and nucleotide sugar metabolism, and ribosome synthesis as the most enriched pathways. Furthermore, among the most common differentially expressed genes, hexose catabolism and iron transport were the most enriched GO terms.ConclusionsOur study is the first to systematically identify and characterize transcription factors involved in the response to H2O2. Based on the transcription factors identified, we found that exposure to H2O2 modulates several downstream gene classes involved in fungal virulence. Overall, this study sheds new light on the metabolism, physiological functions and cellular processes involved in the H2O2-induced oxidative stress response in C. albicans.

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