Secretion of the fungal toxin candidalysin is dependent on conserved precursor peptide sequences.
Journal
Nature microbiology
ISSN: 2058-5276
Titre abrégé: Nat Microbiol
Pays: England
ID NLM: 101674869
Informations de publication
Date de publication:
22 Feb 2024
22 Feb 2024
Historique:
received:
22
11
2022
accepted:
12
01
2024
medline:
23
2
2024
pubmed:
23
2
2024
entrez:
22
2
2024
Statut:
aheadofprint
Résumé
The opportunistic fungal pathogen Candida albicans damages host cells via its peptide toxin, candidalysin. Before secretion, candidalysin is embedded in a precursor protein, Ece1, which consists of a signal peptide, the precursor of candidalysin and seven non-candidalysin Ece1 peptides (NCEPs), and is found to be conserved in clinical isolates. Here we show that the Ece1 polyprotein does not resemble the usual precursor structure of peptide toxins. C. albicans cells are not susceptible to their own toxin, and single NCEPs adjacent to candidalysin are sufficient to prevent host cell toxicity. Using a series of Ece1 mutants, mass spectrometry and anti-candidalysin nanobodies, we show that NCEPs play a role in intracellular Ece1 folding and candidalysin secretion. Removal of single NCEPs or modifications of peptide sequences cause an unfolded protein response (UPR), which in turn inhibits hypha formation and pathogenicity in vitro. Our data indicate that the Ece1 precursor is not required to block premature pore-forming toxicity, but rather to prevent intracellular auto-aggregation of candidalysin sequences.
Identifiants
pubmed: 38388771
doi: 10.1038/s41564-024-01606-z
pii: 10.1038/s41564-024-01606-z
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : Hu 528/20-1
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : Priority Program 2225 Exit Strategies of extracellular pathogens
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : 390713860
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : 210879364
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : 390713860
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : Hu 528/20-1
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : Priority Program 2225 Exit Strategies of extracellular pathogens
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : Priority Program 2225 Exit Strategies of extracellular pathogens
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : Hu- 528/20-1
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : 210879364 Z2
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : 210879364 Z2
Organisme : Wellcome Trust (Wellcome)
ID : 215599_Z_19_Z
Organisme : Wellcome Trust (Wellcome)
ID : 215599_Z_19_Z
Organisme : Wellcome Trust (Wellcome)
ID : 214229/Z/18/Z
Organisme : Leibniz-Gemeinschaft (Leibniz Association)
ID : SAS-2015-HKI-LWC
Organisme : Leibniz-Gemeinschaft (Leibniz Association)
ID : SAS-2015-HKI-LWC
Organisme : Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research)
ID : 13N15705
Organisme : Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research)
ID : FKZ 01K12012
Organisme : Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research)
ID : LPI-BT2, 13N15705
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)
ID : R01AI073289
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)
ID : R01AI073289
Organisme : Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)
ID : CRSII5_173863 /1
Organisme : Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)
ID : CRSII5_173863 /1
Organisme : Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)
ID : CRSII5_173863 /1
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Nature Limited.
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