Efficient in planta production of amidated antimicrobial peptides that are active against drug-resistant ESKAPE pathogens.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
16 03 2023
16 03 2023
Historique:
received:
21
10
2022
accepted:
27
02
2023
entrez:
17
3
2023
pubmed:
18
3
2023
medline:
22
3
2023
Statut:
epublish
Résumé
Antimicrobial peptides (AMPs) are promising next-generation antibiotics that can be used to combat drug-resistant pathogens. However, the high cost involved in AMP synthesis and their short plasma half-life render their clinical translation a challenge. To address these shortcomings, we report efficient production of bioactive amidated AMPs by transient expression of glycine-extended AMPs in Nicotiana benthamiana line expressing the mammalian enzyme peptidylglycine α-amidating mono-oxygenase (PAM). Cationic AMPs accumulate to substantial levels in PAM transgenic plants compare to nontransgenic N. benthamiana. Moreover, AMPs purified from plants exhibit robust killing activity against six highly virulent and antibiotic resistant ESKAPE pathogens, prevent their biofilm formation, analogous to their synthetic counterparts and synergize with antibiotics. We also perform a base case techno-economic analysis of our platform, demonstrating the potential economic advantages and scalability for industrial use. Taken together, our experimental data and techno-economic analysis demonstrate the potential use of plant chassis for large-scale production of clinical-grade AMPs.
Identifiants
pubmed: 36928189
doi: 10.1038/s41467-023-37003-z
pii: 10.1038/s41467-023-37003-z
pmc: PMC10020429
doi:
Substances chimiques
Anti-Bacterial Agents
0
Antimicrobial Cationic Peptides
0
Antimicrobial Peptides
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1464Subventions
Organisme : CIHR
ID : FDN-154287
Pays : Canada
Informations de copyright
© 2023. The Author(s).
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