scholarly journals Cover Image: Candidalysin delivery to the invasion pocket is critical for host epithelial damage induced by Candida albicans (Cellular Microbiology 10/2021)

2021 ◽  
Vol 23 (10) ◽  
Author(s):  
Selene Mogavero ◽  
Frank M. Sauer ◽  
Sascha Brunke ◽  
Stefanie Allert ◽  
Daniela Schulz ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Cover Image ◽  
Epithelial Damage

scholarly journals Protection Against Epithelial Damage During Candida albicans Infection Is Mediated by PI3K/Akt and Mammalian Target of Rapamycin Signaling

2013 ◽  
Vol 209 (11) ◽  
pp. 1816-1826 ◽  
Author(s):  
David L. Moyes ◽  
Chengguo Shen ◽  
Celia Murciano ◽  
Manohursingh Runglall ◽  
Jonathan P. Richardson ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Mammalian Target Of Rapamycin ◽  
Target Of Rapamycin ◽  
Epithelial Damage ◽  
Candida Albicans Infection

scholarly journals Cooperative Role of MAPK Pathways in the Interaction of Candida albicans with the Host Epithelium

2019 ◽  
Vol 8 (1) ◽  
pp. 48 ◽  
Author(s):  
Inês Correia ◽  
Daniel Prieto ◽  
Elvira Román ◽  
Duncan Wilson ◽  
Bernhard Hube ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Epithelial Damage ◽  
Mapk Pathways ◽  
Molecular Approaches ◽  
Abiotic Surfaces ◽  
Solid Media ◽  
Epithelial Invasion ◽  
Semi Solid

Candida albicans is an important human fungal pathogen responsible for tens of millions of infections as well as hundreds of thousands of severe life-threatening infections each year. MAP kinase (MAPK) signal transduction pathways facilitate the sensing and adaptation to external stimuli and control the expression of key virulence factors such as the yeast-to-hypha transition, the biogenesis of the cell wall, and the interaction with the host. In the present study, we have combined molecular approaches and infection biology to analyse the role of C. albicans MAPK pathways during an epithelial invasion. Hog1 was found to be important for adhesion to abiotic surfaces but was dispensable for damage to epithelial cells. The Mkc1 cell wall integrity (CWI) and Cek1 pathways, on the other hand, were both required for oral epithelial damage. Analysis of the ability to penetrate nutrient-rich semi-solid media revealed a cooperative role for Cek1 and Mkc1 in this process. Finally, cek2Δ (as well as cek1Δ) but not mkc1Δ or hog1Δ mutants, exhibited elevated β-glucan unmasking as revealed by immunofluorescence studies. Therefore, the four MAPK pathways play distinct roles in adhesion, epithelial damage, invasion and cell wall remodelling that may contribute to the pathogenicity of C. albicans.

scholarly journals Candida albicans Mrv8, is involved in epithelial damage and biofilm formation

2020 ◽  
Vol 20 (5) ◽  
Author(s):  
Anna Carolina Borges Pereira Costa ◽  
Graziella Nuernberg Back-Brito ◽  
François L Mayer ◽  
Bernhard Hube ◽  
Duncan Wilson
Keyword(s):  
Candida Albicans ◽  
Biofilm Formation ◽  
Transmembrane Protein ◽  
Specific Gene ◽  
Host Pathogen Interactions ◽  
Calcofluor White ◽  
Biofilm Growth ◽  
Epithelial Damage ◽  
Host Pathogen ◽  
Lineage Specific Gene

ABSTRACT Candida albicans is the most common human fungal pathogen that can cause superficial and deep-seated infections in susceptible individuals. Despite its medical importance, the vast majority of C. albicans genes remain of unknown function. Here, we report a role for the lineage-specific gene, MRV8, in host pathogen interactions, mycelial microcolony maturation and biofilm formation. In silico analysis indicated that MRV8 encodes a four-pass transmembrane protein unique to the closely related pathogens C. albicans and Candida dubliniensis. Deletion of MRV8 did not affect C. albicans adherence to, or initial invasion into human oral epithelia, but inhibited mycelial development and strongly reduced epithelial damage. mrv8Δ/Δ cells exhibited a media-dependent defect in biofilm formation and mutant biofilm metabolic activity was enhanced by cyclosporin A. mrv8Δ/Δ biofilms were more tolerant to treatment with caspofungin, but not to fluconazole or amphotericin B. Co-stimulation with calcium chloride and calcofluor white rescued biofilm growth in the presence of caspofungin, and this rescue-effect was Mrv8-dependent. Together, our data demonstrate an important role for a lineage-specific gene (MRV8) in C. albicans biofilm formation, drug tolerance and host–pathogen interactions.

scholarly journals Candidalysin delivery to the invasion pocket is critical for host epithelial damage induced by Candida albicans

2021 ◽  
Author(s):  
Selene Mogavero ◽  
Frank M. Sauer ◽  
Sascha Brunke ◽  
Stefanie Allert ◽  
Daniela Schulz ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Epithelial Damage

scholarly journals Processing of Candida albicans Ece1p Is Critical for Candidalysin Maturation and Fungal Virulence

mBio ◽  
2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Jonathan P. Richardson ◽  
Selene Mogavero ◽  
David L. Moyes ◽  
Mariana Blagojevic ◽  
Thomas Krüger ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Amino Acid ◽  
Fungal Pathogen ◽  
Fungal Virulence ◽  
Epithelial Damage ◽  
Mucosal Infection ◽  
Peptide Toxin ◽  
Opportunistic Fungal Pathogen ◽  
Factor C

ABSTRACTCandida albicansis an opportunistic fungal pathogen responsible for superficial and life-threatening infections in humans. During mucosal infection,C. albicansundergoes a morphological transition from yeast to invasive filamentous hyphae that secrete candidalysin, a 31-amino-acid peptide toxin required for virulence. Candidalysin damages epithelial cell plasma membranes and stimulates the activating protein 1 (AP-1) transcription factor c-Fos (via p38–mitogen-activated protein kinase [MAPK]), and the MAPK phosphatase MKP1 (via extracellular signal-regulated kinases 1 and 2 [ERK1/2]–MAPK), which trigger and regulate proinflammatory cytokine responses, respectively. The candidalysin toxin resides as a discrete cryptic sequence within a larger 271-amino-acid parental preproprotein, Ece1p. Here, we demonstrate that kexin-like proteinases, but not secreted aspartyl proteinases, initiate a two-step posttranslational processing of Ece1p to produce candidalysin. Kex2p-mediated proteolysis of Ece1p after Arg61 and Arg93, but not after other processing sites within Ece1p, is required to generate immature candidalysin from Ece1p, followed by Kex1p-mediated removal of a carboxyl arginine residue to generate mature candidalysin.C. albicansstrains harboring mutations of Arg61 and/or Arg93 did not secrete candidalysin, were unable to induce epithelial damage and inflammatory responsesin vitro, and showed attenuated virulencein vivoin a murine model of oropharyngeal candidiasis. These observations identify enzymatic processing ofC. albicansEce1p by kexin-like proteinases as crucial steps required for candidalysin production and fungal pathogenicity.IMPORTANCECandida albicansis an opportunistic fungal pathogen that causes mucosal infection in millions of individuals worldwide. Successful infection requires the secretion of candidalysin, the first cytolytic peptide toxin identified in any human fungal pathogen. Candidalysin is derived from its parent protein Ece1p. Here, we identify two key amino acids within Ece1p vital for processing and production of candidalysin. Mutations of these residues renderC. albicansincapable of causing epithelial damage and markedly reduce mucosal infectionin vivo. Importantly, candidalysin production requires two individual enzymatic events. The first involves processing of Ece1p by Kex2p, yielding immature candidalysin, which is then further processed by Kex1p to produce the mature toxin. These observations identify important steps forC. albicanspathogenicity at mucosal surfaces.

scholarly journals Candida albicans-Induced Epithelial Damage Mediates Translocation through Intestinal Barriers

mBio ◽  
2018 ◽  
Vol 9 (3) ◽  
Author(s):  
Stefanie Allert ◽  
Toni M. Förster ◽  
Carl-Magnus Svensson ◽  
Jonathan P. Richardson ◽  
Tony Pawlik ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Bloodstream Infections ◽  
Cellular Damage ◽  
Intestinal Damage ◽  
Epithelial Integrity ◽  
Content Type ◽  
Epithelial Damage ◽  
Peptide Toxin ◽  
Fungal Genes

ABSTRACTLife-threatening systemic infections often occur due to the translocation of pathogens across the gut barrier and into the bloodstream. While the microbial and host mechanisms permitting bacterial gut translocation are well characterized, these mechanisms are still unclear for fungal pathogens such asCandida albicans, a leading cause of nosocomial fungal bloodstream infections. In this study, we dissected the cellular mechanisms of translocation ofC. albicansacross intestinal epitheliain vitroand identified fungal genes associated with this process. We show that fungal translocation is a dynamic process initiated by invasion and followed by cellular damage and loss of epithelial integrity. A screen of >2,000C. albicansdeletion mutants identified genes required for cellular damage of and translocation across enterocytes. Correlation analysis suggests that hypha formation, barrier damage above a minimum threshold level, and a decreased epithelial integrity are required for efficient fungal translocation. Translocation occurs predominantly via a transcellular route, which is associated with fungus-induced necrotic epithelial damage, but not apoptotic cell death. The cytolytic peptide toxin ofC. albicans, candidalysin, was found to be essential for damage of enterocytes and was a key factor in subsequent fungal translocation, suggesting that transcellular translocation ofC. albicansthrough intestinal layers is mediated by candidalysin. However, fungal invasion and low-level translocation can also occur via non-transcellular routes in a candidalysin-independent manner. This is the first study showing translocation of a human-pathogenic fungus across the intestinal barrier being mediated by a peptide toxin.IMPORTANCECandida albicans, usually a harmless fungus colonizing human mucosae, can cause lethal bloodstream infections when it manages to translocate across the intestinal epithelium. This can result from antibiotic treatment, immune dysfunction, or intestinal damage (e.g., during surgery). However, fungal processes may also contribute. In this study, we investigated the translocation process ofC. albicansusingin vitrocell culture models. Translocation occurs as a stepwise process starting with invasion, followed by epithelial damage and loss of epithelial integrity. The ability to secrete candidalysin, a peptide toxin deriving from the hyphal protein Ece1, is key:C. albicanshyphae, secreting candidalysin, take advantage of a necrotic weakened epithelium to translocate through the intestinal layer.

Enhanced IgE response to Candida albicans in postoperative invasive candidiasis

1996 ◽  
Vol 26 (4) ◽  
pp. 452-460 ◽  
Author(s):  
J. SAVOLAINEN ◽  
A. RANTALA ◽  
M. NERMES ◽  
L. LEHTONEN ◽  
M. VIANDER
Keyword(s):  
Candida Albicans ◽  
Invasive Candidiasis ◽  
Ige Response

Association between inflammation and epithelial damage-restitution processes in allergic airways in vivo

1997 ◽  
Vol 27 (11) ◽  
pp. 1344-1355 ◽  
Author(s):  
J. S. ERJEFALT ◽  
M. KORSGREN ◽  
M. C. NILSSON ◽  
F. SUNDLER ◽  
C. G. A. PERSSON
Keyword(s):  
Epithelial Damage

Existence of Candida albicans and microorganisms in denture stomatitis patients

1997 ◽  
Vol 24 (10) ◽  
pp. 788-790 ◽  
Author(s):  
Y. KULAK ◽  
A. ARIKAN ◽  
E. KAZAZOGLU
Keyword(s):  
Candida Albicans ◽  
Denture Stomatitis
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