Structural and functional analysis of EntV reveals a 12 amino acid fragment protective against fungal infections.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
13 10 2022
13 10 2022
Historique:
received:
21
04
2022
accepted:
23
09
2022
entrez:
13
10
2022
pubmed:
14
10
2022
medline:
18
10
2022
Statut:
epublish
Résumé
Fungal pathogens are a continuing challenge due to few effective antifungals and a rise in resistance. In previous work, we described the inhibition of Candida albicans virulence following exposure to the 68 amino acid bacteriocin, EntV, secreted by Enterococcus faecalis. Here, to optimize EntV as a potential therapeutic and better understand its antifungal features, an X-ray structure is obtained. The structure consists of six alpha helices enclosing a seventh 16 amino acid helix (α7). The individual helices are tested for antifungal activity using in vitro and nematode infection assays. Interestingly, α7 retains antifungal, but not antibacterial activity and is also effective against Candida auris and Cryptococcus neoformans. Further reduction of α7 to 12 amino acids retains full antifungal activity, and excellent efficacy is observed in rodent models of C. albicans oropharyngeal, systemic, and venous catheter infections. Together, these results showcase EntV-derived peptides as promising candidates for antifungal therapeutic development.
Identifiants
pubmed: 36229448
doi: 10.1038/s41467-022-33613-1
pii: 10.1038/s41467-022-33613-1
pmc: PMC9562342
doi:
Substances chimiques
Amino Acids
0
Antifungal Agents
0
Bacteriocins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
6047Subventions
Organisme : NIDCR NIH HHS
ID : R01 DE027608
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI141349
Pays : United States
Organisme : NIAID NIH HHS
ID : HHSN272201700060C
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI073289
Pays : United States
Informations de copyright
© 2022. The Author(s).
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