4.6 Review

Candidalysin: Connecting the pore forming mechanism of this virulence factor to its immunostimulatory properties

Related references

Note: Only part of the references are listed.
Article Microbiology

Candidalysins Are a New Family of Cytolytic Fungal Peptide Toxins

Jonathan P. Richardson et al.

Summary: The study identifies the first family of peptide toxins, called candidalysins, in human-pathogenic fungi. These toxins are secreted by Candida albicans, Candida dubliniensis, and Candida tropicalis, and are responsible for causing cell damage, calcium influx, and activation of signaling pathways and cytokine secretion. Candidalysins from C. dubliniensis and C. tropicalis exhibit higher damaging and activation potential than C. albicans candidalysin, with faster membrane binding and disruption.
Article Cell Biology

Calcium-dependent ESCRT recruitment and lysosome exocytosis maintain epithelial integrity during Candida albicans invasion

Johannes Westman et al.

Summary: This study reveals two key Ca2+-dependent repair mechanisms employed by epithelial cells to withstand invasion by Candida albicans. These mechanisms help protect epithelial cells from damage caused by candidalysin and the mechanical forces exerted by hyphae, maintaining epithelial integrity.

CELL REPORTS (2022)

Article Multidisciplinary Sciences

Immune regulation by fungal strain diversity in inflammatory bowel disease

Xin Li et al.

Summary: The study reveals the rich genetic diversity of pathogenic Candida albicans strains in the colonic mucosa of patients with inflammatory bowel disease, with some strains having high immune-cell-damaging capacity (HD strains). These strains exacerbate intestinal inflammation in vivo through specific mechanisms, highlighting new insights into host-fungal interactions and potential diagnostic and therapeutic targets for inflammatory diseases.

NATURE (2022)

Article Biochemistry & Molecular Biology

The Candida albicans toxin candidalysin mediates distinct epithelial inflammatory responses through p38 and EGFR-ERK pathways

Spyridoula-Angeliki Nikou et al.

Summary: The fungal pathogen Candida albicans secretes the peptide toxin candidalysin, which activates MAPK p38 and ERK pathways, leading to inflammatory response and immune activation. p38 pathway mainly promotes IL-6 release, Src pathway promotes EGFR phosphorylation, and ERK pathway promotes c-Fos activation and chemokine release.

SCIENCE SIGNALING (2022)

Article Multidisciplinary Sciences

Genetic and phenotypic diversity of fecal Candida albicans strains in irritable bowel syndrome

Isabelle A. M. van Thiel et al.

Summary: Irritable bowel syndrome (IBS) is a common disorder characterized by chronic abdominal pain and changes in bowel movements. Visceral hypersensitivity may be caused by intestinal fungi, but the diversity of fungal communities does not differ between IBS subgroups. The study highlights the importance of conducting strain-specific cause-and-effect studies in IBS research.

SCIENTIFIC REPORTS (2022)

Article Biology

The Candida albicans virulence factor candidalysin polymerizes in solution to form membrane pores and damage epithelial cells

Charles M. Russell et al.

Summary: In this study, the mechanism of Candida albicans infection is revealed, involving a virulence factor called candidalysin (CL). CL damages cell membranes by forming membrane pores, and the formation mechanism involves pre-assembly of CL into polymers in solution, which then form the pores. A CL mutation, G4W, prevents polymer formation and pore formation. This research shows that CL polymerization is a necessary step for damaging cell membranes, and also provides a novel therapeutic target for treating candidiasis.

ELIFE (2022)

Review Immunology

Candida albicansand candidalysin in inflammatory disorders and cancer

Jemima Ho et al.

Summary: Advancements in mycology have highlighted the significant impact of fungal microbes on human health. Candida albicans, a common fungus, not only causes infections but is also associated with various inflammatory disorders, suggesting new avenues for research.

IMMUNOLOGY (2021)

Article Microbiology

Activation of EphA2-EGFR signaling in oral epithelial cells by Candida albicans virulence factors

Marc Swidergall et al.

Summary: During oropharyngeal candidiasis, Candida albicans invades oral epithelial cells and triggers pro-inflammatory response. EphA2 detects beta-glucan and stimulates epithelial cells to release proinflammatory mediators. EGFR interacts with Candida albicans and is activated by Als3 adhesin/invasin and candidalysin pore-forming toxin. EphA2 and EGFR are part of a heteromeric complex and reliant on each other for Candida albicans-induced activation. Als3 enhances targeting of candidalysin, leading to maximal damage to oral epithelial cells and inflammatory cytokine secretion. Candidalysin and EGFR are required for CXCL1/KC and CCL20 production, while Als3 is necessary for TNF alpha but independent for IL-1 alpha and IL-17A. These results demonstrate the complex interplay among host cell receptors and virulence factors during OPC.

PLOS PATHOGENS (2021)

Article Cell Biology

Candidalysin triggers epithelial cellular stresses that induce necrotic death

Mariana Blagojevic et al.

Summary: Candidalysin secreted from Candida albicans causes epithelial cell stress. Candidalysin induces calcium influx and oxidative stress in host cells. Candidalysin induces mitochondrial dysfunction, ATP depletion, and epithelial necrosis.

CELLULAR MICROBIOLOGY (2021)

Article Physiology

Evidence that toxin resistance in poison birds and frogs is not rooted in sodium channel mutations and may rely on toxin sponge proteins

Fayal Abderemane-Ali et al.

Summary: Research shows that the proposed BTX resistance mechanism involving the NaV DIVS6 N-to-T mutation is absent in Pitohui and poison frog NaVs. Additionally, captive-raised poison frogs demonstrate resistance to NaV-directed toxins like BTX and STX, indicating a possible role of toxin sequestration mechanisms in protecting poisonous species.

JOURNAL OF GENERAL PHYSIOLOGY (2021)

Article Microbiology

Candida albicans colonization of the gastrointestinal tract: A double-edged sword

Rebeca Alonso-Monge et al.

Summary: Candida albicans is a common commensal of the vaginal and gastrointestinal tract in humans, but it can also cause severe systemic infections when the microbiota is disturbed and immune defenses are compromised. Recent evidence suggests that despite the risks of colonization, there may be beneficial effects of C. albicans on human health, which have likely driven its establishment as a commensal organism.

PLOS PATHOGENS (2021)

Article Microbiology

A variant ECE1 allele contributes to reduced pathogenicity of Candida albicans during vulvovaginal candidiasis

Junyan Liu et al.

Summary: Vulvovaginal candidiasis caused by Candida albicans poses significant issues for women globally. A conserved variant candidalysin isoform was identified across clinical isolates, with reduced virulence associated with impaired secretion. This study presents a novel mechanism for attenuating C. albicans virulence at the ECE1 locus.

PLOS PATHOGENS (2021)

Review Immunology

New Insights in Candida albicans Innate Immunity at the Mucosa: Toxins, Epithelium, Metabolism, and Beyond

Aize Pellon et al.

FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY (2020)

Article Multidisciplinary Sciences

Candidalysin activates innate epithelial immune responses via epidermal growth factor receptor

Jemima Ho et al.

NATURE COMMUNICATIONS (2019)

Review Microbiology

Candidalysin: discovery and function in Candida albicans infections

Julian R. Naglik et al.

CURRENT OPINION IN MICROBIOLOGY (2019)

Article Microbiology

EphA2 is an epithelial cell pattern recognition receptor for fungal beta-glucans

Marc Swidergall et al.

NATURE MICROBIOLOGY (2018)

Article Immunology

IL-36 and IL-1/IL-17 Drive Immunity to Oral Candidiasis via Parallel Mechanisms

Akash H. Verma et al.

JOURNAL OF IMMUNOLOGY (2018)

Article Medicine, General & Internal

Invasive candidiasis

Peter C. Pappas et al.

NATURE REVIEWS DISEASE PRIMERS (2018)

Article Immunology

Comparative Analysis of the Capacity of the Candida Species To Elicit Vaginal lmmunopathology

Hubertine M. E. Willems et al.

INFECTION AND IMMUNITY (2018)

Review Biochemistry & Molecular Biology

Membrane Active Peptides and Their Biophysical Characterization

Fatma Gizem Avci et al.

BIOMOLECULES (2018)

Article Multidisciplinary Sciences

NLRP3 inflammasome is a key player in human vulvovaginal disease caused by &ITCandida albicans&IT

Elena Roselletti et al.

SCIENTIFIC REPORTS (2017)

Article Microbiology

Oropharyngeal Candidiasis: Fungal Invasion and Epithelial Cell Responses

Marc Swidergall et al.

PLOS PATHOGENS (2017)

Review Microbiology

Candida albicans-epithelial interactions and induction of mucosal innate immunity

Julian R. Naglik et al.

CURRENT OPINION IN MICROBIOLOGY (2017)

Article Gastroenterology & Hepatology

Activation of NLRP3 Inflammasome in Inflammatory Bowel Disease: Differences Between Crohn's Disease and Ulcerative Colitis

Lazaros-Dimitrios Lazaridis et al.

DIGESTIVE DISEASES AND SCIENCES (2017)

Review Microbiology

Pore-forming toxins: ancient, but never really out of fashion

Matteo Dal Peraro et al.

NATURE REVIEWS MICROBIOLOGY (2016)

Article Infectious Diseases

Association of a variable number tandem repeat in the NLRP3 gene in women with susceptibility to RVVC

M. Jaeger et al.

EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES (2016)

Article Multidisciplinary Sciences

Candidalysin is a fungal peptide toxin critical for mucosal infection

David L. Moyes et al.

NATURE (2016)

Review Microbiology

Interactions of fungal pathogens with phagocytes

Lars P. Erwig et al.

NATURE REVIEWS MICROBIOLOGY (2016)

Article Immunology

Oral-resident natural Th17 cells and γδ T cells control opportunistic Candida albicans infections

Heather R. Conti et al.

JOURNAL OF EXPERIMENTAL MEDICINE (2014)

Review Immunology

Candida albicans pathogenicity mechanisms

Francois L. Mayer et al.

VIRULENCE (2013)

Review Microbiology

Pathogenic Pore-Forming Proteins: Function and Host Response

Mirko Bischofberger et al.

CELL HOST & MICROBE (2012)

Article Multidisciplinary Sciences

EGFR and HER2 receptor kinase signaling mediate epithelial cell invasion by Candida albicans during oropharyngeal infection

Weidong Zhu et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2012)

Review Microbiology

Inflammation and gastrointestinal Candida colonization

Carol A. Kumamoto

CURRENT OPINION IN MICROBIOLOGY (2011)

Review Immunology

Sensing damage by the NLRP3 inflammasome

Jaklien C. Leemans et al.

IMMUNOLOGICAL REVIEWS (2011)

Article Immunology

Th17 cells and IL-17 receptor signaling are essential for mucosal host defense against oral candidiasis

Heather R. Conti et al.

JOURNAL OF EXPERIMENTAL MEDICINE (2009)

Review Microbiology

An integrated model of the recognition of Candida albicans by the innate immune system

Mihai G. Netea et al.

NATURE REVIEWS MICROBIOLOGY (2008)

Article Biochemistry & Molecular Biology

Als3 is a Candida albicans invasin that binds to cadherins and induces endocytosis by host cells

Quynh T. Phan et al.

PLOS BIOLOGY (2007)

Review Biochemistry & Molecular Biology

Mode of action of membrane active antimicrobial peptides

Y Shai

BIOPOLYMERS (2002)