The MP65 gene is required for cell wall integrity, adherence to epithelial cells and biofilm formation in Candida albicans

ABSTRACT Candida albicans ECM33 encodes a glycosylphosphatidylinositol-linked cell wall protein that is important for cell wall integrity. It is also critical for normal virulence in the mouse model of hematogenously disseminated candidiasis. To identify potential mechanisms through which Ecm33p contributes to virulence, we investigated the interactions of C. albicans ecm33Δ mutants with endothelial cells and the FaDu oral epithelial cell line in vitro. The growth rate of blastospores of strains containing either one or no intact copies of ECM33 was 50% slower than that of strains containing two intact copies of ECM33. However, all strains germinated at the same rate, forming similar-length hyphae on endothelial cells and oral epithelial cells. Strains containing either one or no intact copies of ECM33 had modestly reduced adherence to both types of host cells, and a markedly reduced capacity to invade and damage these cells. Saccharomyces cerevisiae expressing C. albicans ECM33 did not adhere to or invade epithelial cells, suggesting that Ecm33p by itself does not act as an adhesin or invasin. Examination of ecm33Δ mutants by transmission electron microscopy revealed that the cell wall of these strains had an abnormally electron-dense outer mannoprotein layer, which may represent a compensatory response to reduced cell wall integrity. The hyphae of these mutants also had aberrant surface localization of the adhesin Als1p. Collectively, these results suggest that Ecm33p is required for normal cell wall architecture as well as normal function and expression of cell surface proteins in C. albicans.

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Candida albicans cell wall integrity transcription factors regulate polymicrobial biofilm formation with Streptococcus gordonii

PeerJ ◽

10.7717/peerj.7870 ◽

2019 ◽

Vol 7 ◽

pp. e7870 ◽

Cited By ~ 4

Author(s):

Jennifer Chinnici ◽

Lisa Yerke ◽

Charlene Tsou ◽

Sujay Busarajan ◽

Ryan Mancuso ◽

...

Keyword(s):

Cell Wall ◽

Candida Albicans ◽

Transcription Factors ◽

Biofilm Formation ◽

Mixed Cultures ◽

Cell Wall Integrity ◽

Antibiotic Tolerance ◽

Streptococcus Gordonii ◽

Knock Out

Polymicrobial biofilms play important roles in oral and systemic infections. The oral plaque bacterium Streptococcus gordonii is known to attach to the hyphal cell wall of the fungus Candida albicans to form corn-cob like structures in biofilms. However, the role of C. albicans in formation of polymicrobial biofilms is not completely understood. The objective of this study was to determine the role of C. albicans transcription factors in regulation of polymicrobial biofilms and antibiotic tolerance of S. gordonii. The proteins secreted by C. albicans and S. gordonii in mixed planktonic cultures were determined using mass spectrometry. Antibiotic tolerance of S. gordonii to ampicillin and erythromycin was determined in mixed cultures and mixed biofilms with C. albicans. Additionally, biofilm formation of S. gordonii with C. albicans knock-out mutants of 45 transcription factors that affect cell wall integrity, filamentous growth and biofilm formation was determined. Furthermore, these mutants were also screened for antibiotic tolerance in mixed biofilms with S. gordonii. Analysis of secreted proteomes resulted in the identification of proteins being secreted exclusively in mixed cultures. Antibiotic testing showed that S. gordonii had significantly increased survival in mixed planktonic cultures with antibiotics as compared to single cultures. C. albicans mutants of transcription factors Sfl2, Brg1, Leu3, Cas5, Cta4, Tec1, Tup1, Rim101 and Efg1 were significantly affected in mixed biofilm formation. Also mixed biofilms of S. gordonii with mutants of C. albicans transcription factors, Tec1 and Sfl2, had significantly reduced antibiotic tolerance as compared to control cultures. Our data indicates that C. albicans may have an important role in mixed biofilm formation as well as antibiotic tolerance of S. gordonii in polymicrobial biofilms. C. albicans may play a facilitating role than being just an innocent bystander in oral biofilms and infections.

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Candida albicans Aro1 affects cell wall integrity, biofilm formation and virulence

Journal of Microbiology Immunology and Infection ◽

10.1016/j.jmii.2018.04.002 ◽

2020 ◽

Vol 53 (1) ◽

pp. 115-124 ◽

Cited By ~ 3

Author(s):

Ying-Chieh Yeh ◽

Hung-Yen Wang ◽

Chung-Yu Lan

Keyword(s):

Cell Wall ◽

Candida Albicans ◽

Biofilm Formation ◽

Cell Wall Integrity

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Yeast casein kinase 2 governs morphology, biofilm formation, cell wall integrity, and host cell damage of Candida albicans

PLoS ONE ◽

10.1371/journal.pone.0187721 ◽

2017 ◽

Vol 12 (11) ◽

pp. e0187721 ◽

Cited By ~ 4

Author(s):

Sook-In Jung ◽

Natalie Rodriguez ◽

Jihyun Irrizary ◽

Karl Liboro ◽

Thania Bogarin ◽

...

Keyword(s):

Cell Wall ◽

Candida Albicans ◽

Host Cell ◽

Biofilm Formation ◽

Cell Damage ◽

Casein Kinase ◽

Casein Kinase 2 ◽

Cell Wall Integrity

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

PLoS Pathogens ◽

10.1371/journal.ppat.1002384 ◽

2011 ◽

Vol 7 (11) ◽

pp. e1002384 ◽

Cited By ~ 10

Author(s):

Manimala Sen ◽

Bhavin Shah ◽

Srabanti Rakshit ◽

Vijender Singh ◽

Bhavna Padmanabhan ◽

...

Keyword(s):

Cell Wall ◽

Candida Albicans ◽

Cell Wall Integrity ◽

Dehydratase Activity

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Candida albicans Sun41p, a Putative Glycosidase, Is Involved in Morphogenesis, Cell Wall Biogenesis, and Biofilm Formation

Eukaryotic Cell ◽

10.1128/ec.00285-07 ◽

2007 ◽

Vol 6 (11) ◽

pp. 2056-2065 ◽

Cited By ~ 58

Author(s):

Ekkehard Hiller ◽

Sonja Heine ◽

Herwig Brunner ◽

Steffen Rupp

Keyword(s):

Cell Wall ◽

Candida Albicans ◽

Biofilm Formation ◽

Cell Monolayer ◽

The Sun ◽

Calcofluor White ◽

Cellular Processes ◽

Cell Wall Biogenesis ◽

Reduced Adherence ◽

Higher Sensitivity

ABSTRACT The SUN gene family has been defined in Saccharomyces cerevisiae and comprises a fungus-specific family of proteins which show high similarity in their C-terminal domains. Genes of this family are involved in different cellular processes, like DNA replication, aging, mitochondrial biogenesis, and cytokinesis. In Candida albicans the SUN family comprises two genes, SUN41 and SIM1. We demonstrate that C. albicans mutants lacking SUN41 show similar defects as found for S. cerevisiae, including defects in cytokinesis. In addition, the SUN41 mutant showed a higher sensitivity towards the cell wall-disturbing agent Congo red, whereas no difference was observed in the presence of calcofluor white. Compared to the wild type, SUN41 deletion strains exhibited a defect in biofilm formation, a reduced adherence on a Caco-2 cell monolayer, and were unable to form hyphae on solid medium under the conditions tested. Interestingly, Sun41p was found to be secreted in the medium of cells growing as blastospores as well as those forming hyphae. Our results support a function of SUN41p as a glycosidase involved in cytokinesis, cell wall biogenesis, adhesion to host tissue, and biofilm formation, indicating an important role in the host-pathogen interaction.

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A small G protein Rhb1 and a GTPase-activating protein Tsc2 involved in nitrogen starvation-induced morphogenesis and cell wall integrity of Candida albicans

Fungal Genetics and Biology ◽

10.1016/j.fgb.2008.11.008 ◽

2009 ◽

Vol 46 (2) ◽

pp. 126-136 ◽

Cited By ~ 37

Author(s):

Chang-Chih Tsao ◽

Yu-Ting Chen ◽

Chung-Yu Lan

Keyword(s):

Cell Wall ◽

Candida Albicans ◽

G Protein ◽

Nitrogen Starvation ◽

Cell Wall Integrity ◽

Gtpase Activating Protein ◽

Small G Protein

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Determination of the effects of cinnamon bark fractions on Candida albicans and oral epithelial cells

BMC Complementary and Alternative Medicine ◽

10.1186/s12906-019-2730-2 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 6

Author(s):

Marie-Pier Veilleux ◽

Daniel Grenier

Keyword(s):

Candida Albicans ◽

Epithelial Cells ◽

Essential Oil ◽

Biofilm Formation ◽

Epithelial Barrier ◽

Cinnamon Oil ◽

Cinnamon Bark ◽

Oral Epithelial Cells ◽

Oral Epithelial

Abstract Background Candida albicans is an opportunistic pathogen that causes oral candidiasis and denture stomatitis. It has also been reported to infect oral mucositis lesions in patients who suffer from cancer affecting the head and neck and who receive chemotherapy and radiotherapy treatments. This study aimed to investigate the effects of two cinnamon bark fractions, i.e., an essential oil and an aqueous extract enriched in proanthocyanidins (Cinnulin PF®) on growth, biofilm formation, and adherence properties of C. albicans as well as on oral epithelial cells (barrier integrity, inflammatory response). Methods A microplate dilution assay was used to determine antifungal and anti-biofilm properties. A fluorescent assay was used to determine C. albicans adherence to oral epithelial cells. Cytotoxicity toward oral epithelial cells was assessed by determination of cell metabolic activity. Tight junction integrity of gingival keratinocytes was assessed by determination of transepithelial electrical resistance. IL-6 and IL-8 secretion by TNFα-stimulated oral epithelial cells was quantified by ELISA. Results While Cinnulin PF® did not reduce C. albicans growth, the cinnamon bark oil exhibited high antifungal activity with minimum inhibitory concentrations and minimum fungicidal concentrations in the range of 0.039 to 0.078%. The cinnamon oil was also active against a pre-formed C. albicans biofilm. Interestingly, Cinnulin PF® prevented biofilm formation by C. albicans and attenuated its adherence to oral epithelial cells. At their effective concentrations, the cinnamon oil and the Cinnulin PF® displayed no significant cytotoxicity against oral epithelial cells. In an in vitro model, both cinnamon fractions reinforced the integrity of the oral epithelial barrier. Lastly, Cinnulin PF® inhibited the secretion of interleukin-6 and interleukin-8 by oral epithelial cells stimulated with TNF-α. Conclusion By their ability to attenuate growth, biofilm formation and adherence property of C. albicans, to reinforce the epithelial barrier function, and to exert anti-inflammatory properties the two cinnamon fractions (essential oil, Cinnulin PF®) investigated in the present study may be promising agents for treating oral infections involving C. albicans.

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