UDP-glucose 4, 6-dehydratase Activity Plays an Important Role in Maintaining Cell Wall Integrity and Virulence of Candida albicans

Sen, Manimala; Shah, Bhavin; Rakshit, Sourav; Singh, Vijender; Padmanabhan, Bhavna; Ponnusamy, Manikandan; Pari, Koteppa; Vishwakarma, Ram A.; Nandi, Dipankar; Sadhale, Parag P.

doi:10.1371/journal.ppat.1002384

Cited by 19 publications

(12 citation statements)

References 60 publications

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“…However, by day seven, as the mutant cells show a higher susceptibility to immune effector cells they are more easily cleared. Other studies with mutants that affect cell wall organization, including septin organization, also showed decreased virulence in the murine model of disseminated candidiasis, such as PPZ1 , PGA13 , GAL102 , CDC10 , CDC11 [49], [56]–[59]. Complementation of RLM1 partially restored the virulence phenotype, indicating that gene dosage is important.…”

Section: Discussionmentioning

confidence: 89%

Participation of Candida albicans Transcription Factor RLM1 in Cell Wall Biogenesis and Virulence

et al. 2014

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Candida albicans cell wall is important for growth and interaction with the environment. RLM1 is one of the putative transcription factors involved in the cell wall integrity pathway, which plays an important role in the maintenance of the cell wall integrity. In this work we investigated the involvement of RLM1 in the cell wall biogenesis and in virulence. Newly constructed C. albicans Δ/Δrlm1 mutants showed typical cell wall weakening phenotypes, such as hypersensitivity to Congo Red, Calcofluor White, and caspofungin (phenotype reverted in the presence of sorbitol), confirming the involvement of RLM1 in the cell wall integrity. Additionally, the cell wall of C. albicans Δ/Δrlm1 showed a significant increase in chitin (213%) and reduction in mannans (60%), in comparison with the wild-type, results that are consistent with cell wall remodelling. Microarray analysis in the absence of any stress showed that deletion of RLM1 in C. albicans significantly down-regulated genes involved in carbohydrate catabolism such as DAK2, GLK4, NHT1 and TPS1, up-regulated genes involved in the utilization of alternative carbon sources, like AGP2, SOU1, SAP6, CIT1 or GAL4, and genes involved in cell adhesion like ECE1, ALS1, ALS3, HWP1 or RBT1. In agreement with the microarray results adhesion assays showed an increased amount of adhering cells and total biomass in the mutant strain, in comparison with the wild-type. C. albicans mutant Δ/Δrlm1 strain was also found to be less virulent than the wild-type and complemented strains in the murine model of disseminated candidiasis. Overall, we showed that in the absence of RLM1 the modifications in the cell wall composition alter yeast interaction with the environment, with consequences in adhesion ability and virulence. The gene expression findings suggest that this gene participates in the cell wall biogenesis, with the mutant rearranging its metabolic pathways to allow the use of alternative carbon sources.

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Section: Discussionmentioning

confidence: 89%

Participation of Candida albicans Transcription Factor RLM1 in Cell Wall Biogenesis and Virulence

et al. 2014

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“…For example, GAL102 and the PMT ( P rotein M annosyl T ransferase) gene family govern protein mannosylation (62,63). The impact of respective mutations on biofilm formation may result from altered adhesin glycosylation.…”

Section: The Cell Surface and Adherencementioning

confidence: 99%

Candida albicans Biofilm Development and Its Genetic Control

Desai

Mitchell

2015

Microbiol Spectr

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The fungus Candida albicans is a major source of device-associated infection because of its capacity for biofilm formation. It is part of the natural mucosal flora, and thus has access to available niches that can lead to infection. In this chapter we discuss the major properties of C. albicans biofilms, and the insight that has been gleaned from their genetic determinants. Our specific areas of focus include biofilm structure and development, cell morphology and biofilm formation, biofilm-associated gene expression, the cell surface and adherence, the extracellular matrix, biofilm metabolism, and biofilm drug resistance.

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“…Nonetheless, the regulation of the GAL genes may be physiologically significant. Recent studies indicate that the GAL10 and GAL102 gene are needed for cell wall integrity, even when grown in the presence of other sugars [40, 41]. …”

Section: Glcnac Functions In C Albicans and Other Fungimentioning

confidence: 99%

N-Acetylglucosamine Functions in Cell Signaling

2012

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The amino sugar N-acetylglucosamine (GlcNAc) is well known for the important structural roles that it plays at the cell surface. It is a key component of bacterial cell wall peptidoglycan, fungal cell wall chitin, and the extracellular matrix of animal cells. Interestingly, recent studies have also identified new roles for GlcNAc in cell signaling. For example, GlcNAc stimulates the human fungal pathogen Candida albicans to undergo changes in morphogenesis and expression of virulence genes. Pathogenic E. coli responds to GlcNAc by altering the expression of fimbriae and CURLI fibers that promote biofilm formation and GlcNAc stimulates soil bacteria to undergo changes in morphogenesis and production of antibiotics. Studies with animal cells have revealed that GlcNAc influences cell signaling through the posttranslational modification of proteins by glycosylation. O-linked attachment of GlcNAc to Ser and Thr residues regulates a variety of intracellular proteins, including transcription factors such as NFκB, c-myc, and p53. In addition, the specificity of Notch family receptors for different ligands is altered by GlcNAc attachment to fucose residues in the extracellular domain. GlcNAc also impacts signal transduction by altering the degree of branching of N-linked glycans, which influences cell surface signaling proteins. These emerging roles of GlcNAc as an activator and mediator of cellular signaling in fungi, animals, and bacteria will be the focus of this paper.

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UDP-glucose 4, 6-dehydratase Activity Plays an Important Role in Maintaining Cell Wall Integrity and Virulence of Candida albicans

Cited by 19 publications

References 60 publications

Participation of Candida albicans Transcription Factor RLM1 in Cell Wall Biogenesis and Virulence

Participation of Candida albicans Transcription Factor RLM1 in Cell Wall Biogenesis and Virulence

Candida albicans Biofilm Development and Its Genetic Control

N-Acetylglucosamine Functions in Cell Signaling

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