Candida albicans translocation through the intestinal epithelial barrier is promoted by fungal zinc acquisition and limited by NFκB-mediated barrier protection.
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
Mar 2024
Mar 2024
Historique:
received:
20
07
2023
accepted:
06
02
2024
medline:
4
3
2024
pubmed:
1
3
2024
entrez:
1
3
2024
Statut:
epublish
Résumé
The opportunistic fungal pathogen Candida albicans thrives on human mucosal surfaces as a harmless commensal, but frequently causes infections under certain predisposing conditions. Translocation across the intestinal barrier into the bloodstream by intestine-colonizing C. albicans cells serves as the main source of disseminated candidiasis. However, the host and microbial mechanisms behind this process remain unclear. In this study we identified fungal and host factors specifically involved in infection of intestinal epithelial cells (IECs) using dual-RNA sequencing. Our data suggest that host-cell damage mediated by the peptide toxin candidalysin-encoding gene ECE1 facilitates fungal zinc acquisition. This in turn is crucial for the full virulence potential of C. albicans during infection. IECs in turn exhibit a filamentation- and damage-specific response to C. albicans infection, including NFκB, MAPK, and TNF signaling. NFκB activation by IECs limits candidalysin-mediated host-cell damage and mediates maintenance of the intestinal barrier and cell-cell junctions to further restrict fungal translocation. This is the first study to show that candidalysin-mediated damage is necessary for C. albicans nutrient acquisition during infection and to explain how IECs counteract damage and limit fungal translocation via NFκB-mediated maintenance of the intestinal barrier.
Identifiants
pubmed: 38427950
doi: 10.1371/journal.ppat.1012031
pii: PPATHOGENS-D-23-01201
pmc: PMC10907035
doi:
Substances chimiques
Zinc
J41CSQ7QDS
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1012031Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/V033417/1
Pays : United Kingdom
Organisme : NIDCR NIH HHS
ID : R01 DE022550
Pays : United States
Organisme : NIDCR NIH HHS
ID : R37 DE022550
Pays : United States
Informations de copyright
Copyright: © 2024 Sprague et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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