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A Novel Role for the Transcription Factor Cwt1p as a Negative Regulator of Nitrosative Stress in Candida albicans  [PDF]
Adnane Sellam, Faiza Tebbji, Malcolm Whiteway, André Nantel
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0043956
Abstract: The ability of Candida albicans to survive in the presence of nitrosative stress during the initial contact with the host immune system is crucial for its ability to colonize mammalian hosts. Thus, this fungus must activate robust mechanisms to neutralize and repair nitrosative-induced damage. Until now, very little was known regarding the regulatory circuits associated with reactive nitrogen species detoxification in fungi. To gain insight into the transcriptional regulatory networks controlling nitrosative stress response (NRS) in C. albicans a compilation of transcriptional regulator-defective mutants were screened. This led to the identification of Cwt1p as a negative regulator of NSR. By combining genome-wide location and expression analyses, we have characterized the Cwt1p regulon and demonstrated that Cwt1p is directly required for proper repression of the flavohemoglobin Yhb1p, a key NO-detoxification enzyme. Furthermore, Cwt1p operates both by activating and repressing genes of specific functions solicited upon NSR. Additionally, we used Gene Set Enrichment Analysis to reinvestigate the C. albicans NSR-transcriptome and demonstrate a significant similarity with the transcriptional profiles of C. albicans interacting with phagocytic host-cells. In summary, we have characterized a novel negative regulator of NSR and bring new insights into the transcriptional regulatory network governing fungal NSR.
In vivo efficacy of alkaline peroxide tablets and mouthwashes on Candida albicans in patients with denture stomatitis
Uludamar, Altay;?zkan, Yasemin Kulak;Kadir, Tanju;Ceyhan, Ismail;
Journal of Applied Oral Science , 2010, DOI: 10.1590/S1678-77572010000300017
Abstract: objective: effective cleaning of dentures is important for the maintenance of good oral hygiene for denture stomatitis patients. the in vivo efficacy of three different brands of alkaline peroxide tablets (polident, efferdent, and fittydent) and two mouthwashes (closys ii and corsodyl) to eliminate candida albicans on dentures was evaluated in this in vivo study. material and methods: ninety denture wearers with clinical evidence of denture stomatitis were randomly divided into 5 test groups and 1 control group. each group was further divided into three subgroups in which the dentures were subjected to 15-, 30-, and 60-min disinfection procedures. the dentures of each test group were treated with one of the cleaners, while those of the control group were treated with distilled water. swab samples from the palatal surfaces (2 cm x 2 cm template delimited area) of the upper dentures were obtained before and after 15, 30, and 60 min periods of cleaner use and examined mycologically. results: the reduction in the number of colony-forming units (cfu) of c. albicans before, and after 15, 30, and 60 min of use of closys ii and corsodyl was significantly greater than that of the control group (p<0.05). moreover, there was no statistically significant difference (p>0.05) among polident, efferdent and the control group in any of the treatment periods. dentures treated with fittydent appeared to have a significantly greater reduction in the number of candida spp. only after 60 min of treatment. conclusions: the results of this study showed that the use of mouthwashes significantly reduced the number of microorganisms on dentures.
The Candida albicans-Specific Gene EED1 Encodes a Key Regulator of Hyphal Extension  [PDF]
Ronny Martin,Gary P. Moran,Ilse D. Jacobsen,Antje Heyken,Jenny Domey,Derek J. Sullivan,Oliver Kurzai,Bernhard Hube
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0018394
Abstract: The extension of germ tubes into elongated hyphae by Candida albicans is essential for damage of host cells. The C. albicans-specific gene EED1 plays a crucial role in this extension and maintenance of filamentous growth. eed1Δ cells failed to extend germ tubes into long filaments and switched back to yeast growth after 3 h of incubation during growth on plastic surfaces. Expression of EED1 is regulated by the transcription factor Efg1 and ectopic overexpression of EED1 restored filamentation in efg1Δ. Transcriptional profiling of eed1Δ during infection of oral tissue revealed down-regulation of hyphal associated genes including UME6, encoding another key transcriptional factor. Ectopic overexpression of EED1 or UME6 rescued filamentation and damage potential in eed1Δ. Transcriptional profiling during overexpression of UME6 identified subsets of genes regulated by Eed1 or Ume6. These data suggest that Eed1 and Ume6 act in a pathway regulating maintenance of hyphal growth thereby repressing hyphal-to-yeast transition and permitting dissemination of C. albicans within epithelial tissues.
The NDR/LATS Kinase Cbk1 Controls the Activity of the Transcriptional Regulator Bcr1 during Biofilm Formation in Candida albicans  [PDF]
Pilar Gutiérrez-Escribano,Ute Zeidler,M. Belén Suárez,Sophie Bachellier-Bassi,Andrés Clemente-Blanco,Julie Bonhomme,Carlos R. Vázquez de Aldana,Christophe d'Enfert,Jaime Correa-Bordes
PLOS Pathogens , 2012, DOI: 10.1371/journal.ppat.1002683
Abstract: In nature, many microorganisms form specialized complex, multicellular, surface-attached communities called biofilms. These communities play critical roles in microbial pathogenesis. The fungal pathogen Candida albicans is associated with catheter-based infections due to its ability to establish biofilms. The transcription factor Bcr1 is a master regulator of C. albicans biofilm development, although the full extent of its regulation remains unknown. Here, we report that Bcr1 is a phosphoprotein that physically interacts with the NDR kinase Cbk1 and undergoes Cbk1-dependent phosphorylation. Mutating the two putative Cbk1 phosphoacceptor residues in Bcr1 to alanine markedly impaired Bcr1 function during biofilm formation and virulence in a mouse model of disseminated candidiasis. Cells lacking Cbk1, or any of its upstream activators, also had reduced biofilm development. Notably, mutating the two putative Cbk1 phosphoacceptor residues in Bcr1 to glutamate in cbk1Δ cells upregulated the transcription of Bcr1-dependent genes and partially rescued the biofilm defects of a cbk1Δ strain. Therefore, our data uncovered a novel role of the NDR/LATS kinase Cbk1 in the regulation of biofilm development through the control of Bcr1.
Aft2, a Novel Transcription Regulator, Is Required for Iron Metabolism, Oxidative Stress, Surface Adhesion and Hyphal Development in Candida albicans  [PDF]
Ning Xu, Xinxin Cheng, Qilin Yu, Kefan Qian, Xiaohui Ding, Ruming Liu, Biao Zhang, Laijun Xing, Mingchun Li
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0062367
Abstract: Morphological transition and iron metabolism are closely relevant to Candida albicans pathogenicity and virulence. In our previous study, we demonstrated that C. albicans Aft2 plays an important role in ferric reductase activity and virulence. Here, we further explored the roles of C. albicans Aft2 in numerous cellular processes. We found that C. albicans Aft2 exhibited an important role in iron metabolism through bi-directional regulation effects on iron-regulon expression. Deletion of AFT2 reduced cellular iron accumulation under iron-deficient conditions. Furthermore, both reactive oxygen species (ROS) generation and superoxide dismutase (SOD) activity were remarkably increased in the aft2Δ/Δ mutant, which were thought to be responsible for the defective responses to oxidative stress. However, we found that over-expression of C. albicans AFT2 under the regulation of the strong PGK1 promoter could not effectively rescue Saccharomyces cerevisiae aft1Δ mutant defects in some cellular processes, such as cell-wall assembly, ion homeostasis and alkaline resistance, suggesting a possibility that C. albicans Aft2 weakened its functional role of regulating some cellular metabolism during the evolutionary process. Interestingly, deletion of AFT2 in C. albicans increased cell surface hydrophobicity, cell flocculation and the ability of adhesion to polystyrene surfaces. In addition, our results also revealed that C. albicans Aft2 played a dual role in regulating hypha-specific genes under solid and liquid hyphal inducing conditions. Deletion of AFT2 caused an impaired invasive growth in solid medium, but an increased filamentous aggregation and growth in liquid conditions. Moreover, iron deficiency and environmental cues induced nuclear import of Aft2, providing additional evidence for the roles of Aft2 in transcriptional regulation.
Modulation of Phagosomal pH by Candida albicans Promotes Hyphal Morphogenesis and Requires Stp2p, a Regulator of Amino Acid Transport  [PDF]
Slavena Vylkova,Michael C. Lorenz
PLOS Pathogens , 2014, DOI: doi/10.1371/journal.ppat.1003995
Abstract: Candida albicans, the most important fungal pathogen of humans, has a unique interaction with macrophages in which phagocytosis induces a switch from the yeast to hyphal form, allowing it to escape by rupturing the immune cell. While a variety of factors induce this switch in vitro, including neutral pH, it is not clear what triggers morphogenesis within the macrophage where the acidic environment should inhibit this transition. In vitro, C. albicans grown in similar conditions in which amino acids are the primary carbon source generate large quantities of ammonia to raise the extracellular pH and induce the hyphal switch. We show here that C. albicans cells neutralize the macrophage phagosome and that neutral pH is a key inducer of germination in phagocytosed cells by using a mutant lacking STP2, a transcription factor that regulates the expression of multiple amino acid permeases, that is completely deficient in alkalinization in vitro. Phagocytosed stp2Δ mutant cells showed significant reduction in hypha formation and escaped from macrophages less readily compared to wild type cells; as a result stp2Δ mutant cells were killed at a higher rate and caused less damage to RAW264.7 macrophages. Stp2p-regulated import leads to alkalinization of the phagosome, since the majority of the wild type cells fail to co-localize with acidophilic dyes, whereas the stp2Δ mutant cells were located in acidic phagosomes. Furthermore, stp2Δ mutant cells were able to form hyphae and escape from neutral phagosomes, indicating that the survival defect in these cells was pH dependent. Finally, these defects are reflected in an attenuation of virulence in a mouse model of disseminated candidiasis. Altogether our results suggest that C. albicans utilizes amino acids to promote neutralization of the phagosomal pH, hyphal morphogenesis, and escape from macrophages.
Endoftalmite por Candida albicans
Serracarbassa, Pedro Duraes;Dotto, Patrícia;
Arquivos Brasileiros de Oftalmologia , 2003, DOI: 10.1590/S0004-27492003000500027
Abstract: the author describes epidemiological, histopathological and clinical aspects of endogenous candida albicans endophthalmitis. he also presents new diagnostic methods and therapeutical options to treat intraocular fungal infections, based on literature review.
Portrait of Candida albicans Adherence Regulators  [PDF]
Jonathan S. Finkel,Wenjie Xu,David Huang,Elizabeth M. Hill,Jigar V. Desai,Carol A. Woolford,Jeniel E. Nett,Heather Taff,Carmelle T. Norice,David R. Andes,Frederick Lanni,Aaron P. Mitchell
PLOS Pathogens , 2012, DOI: 10.1371/journal.ppat.1002525
Abstract: Cell-substrate adherence is a fundamental property of microorganisms that enables them to exist in biofilms. Our study focuses on adherence of the fungal pathogen Candida albicans to one substrate, silicone, that is relevant to device-associated infection. We conducted a mutant screen with a quantitative flow-cell assay to identify thirty transcription factors that are required for adherence. We then combined nanoString gene expression profiling with functional analysis to elucidate relationships among these transcription factors, with two major goals: to extend our understanding of transcription factors previously known to govern adherence or biofilm formation, and to gain insight into the many transcription factors we identified that were relatively uncharacterized, particularly in the context of adherence or cell surface biogenesis. With regard to the first goal, we have discovered a role for biofilm regulator Bcr1 in adherence, and found that biofilm regulator Ace2 is a major functional target of chromatin remodeling factor Snf5. In addition, Bcr1 and Ace2 share several target genes, pointing to a new connection between them. With regard to the second goal, our findings reveal existence of a large regulatory network that connects eleven adherence regulators, the zinc-response regulator Zap1, and approximately one quarter of the predicted cell surface protein genes in this organism. This limited yet sensitive glimpse of mutant gene expression changes had thus defined one of the broadest cell surface regulatory networks in C. albicans.
Espondilodiscitis por Candida albicans
De Luca,Silvina; Mondello,Eduardo; Oviedo,Soledad; Tisser,Laura; Eyheremendy,Eduardo P.; Rica,Carlos;
Revista argentina de radiolog?-a , 2008,
Abstract: purpose: to describe candida albicans spondylodiscitis distinctive imaging findings and treatment. the authors reported a 51 years old, male inmunocompromised patient with fever and lumbar pain. mr findings include bone marrow hypointense signal intensity in t2 weighted of affected vertebral bodies and intense discovertebral enhancement. candida albicans spondylodiscitis should be considered as one of the differential diagnosis of an inmunocompromised patient with lumbar pain and lumbar atypical findings at mr. biopsy sample is required in order to reach final diagnosis. the first choice treatment is antyfungal drugs although in certain cases surgery is required. rapid recognition of distinctive imaging findings avoid missdiagnosis and treatment delays.
Nuclear Proteins Associated with Hyphen Growth in Candida albicans
Alsheyab Fawzi
Journal of Biological Sciences , 2007,
Abstract: Candida albicans is an opportunistic fungus and the most prevalent among human pathogenic yeasts. The Candida spp. are dimorphic fungi with mycelium (M) and budding yeast (B) growth phases. Dimorphism of C. albicans is believed to be a critical component of pathogenesis, to ensure whether the yeast form or the hyphal form is primary responsible for pathogenicity. Growth-form-specific transcripts of C. albicans were characterized using ddRT-PCR to ascertain their fundamental differentiation process. The isolated transcript gene (cam3) was identified when it`s being expressed during morphogenesis utilizing North blot technique. Differentially expressed mRNAs from both budding and mycelia cultures were characterized for sequence and time of expression during growth phases. One cDNA was identified for transcripts which is apparently unique to hyphal cells. It appears to encode protein homologous to known nuclear proteins. The cDNA (cam3) encodes a polypeptide which shows intriguing similarities to two proteins involved in gene and cell cycle regulation. Portions of the gene align with a protein which interacts with Sin3, a general transcriptional regulator in S. cerevisiae. Other portions appear homologous to proteins involved in uracil anabolism.
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