Synthetic Antibiotic Derived from Sequences Encrypted in a Protein from Human Plasma

Encrypted peptides have been recently found in the human proteome and represent a potential class of antibiotics. Here we report three peptides derived from the human apolipoprotein B (residues 887–922) that exhibited potent antimicrobial activity against drug-resistant Klebsiella pneumoniae, Acinet...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:ACS nano 2022-02, Vol.16 (2), p.1880-1895
Hauptverfasser: Cesaro, Angela, Torres, Marcelo D. T, Gaglione, Rosa, Dell’Olmo, Eliana, Di Girolamo, Rocco, Bosso, Andrea, Pizzo, Elio, Haagsman, Henk P, Veldhuizen, Edwin J. A, de la Fuente-Nunez, Cesar, Arciello, Angela
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:Encrypted peptides have been recently found in the human proteome and represent a potential class of antibiotics. Here we report three peptides derived from the human apolipoprotein B (residues 887–922) that exhibited potent antimicrobial activity against drug-resistant Klebsiella pneumoniae, Acinetobacter baumannii, and Staphylococci both in vitro and in an animal model. The peptides had excellent cytotoxicity profiles, targeted bacteria by depolarizing and permeabilizing their cytoplasmic membrane, inhibited biofilms, and displayed anti-inflammatory properties. Importantly, the peptides, when used in combination, potentiated the activity of conventional antibiotics against bacteria and did not select for bacterial resistance. To ensure translatability of these molecules, a protease resistant retro-inverso variant of the lead encrypted peptide was synthesized and demonstrated anti-infective activity in a preclinical mouse model. Our results provide a link between human plasma and innate immunity and point to the blood as a source of much-needed antimicrobials.
ISSN:1936-0851
1936-086X
DOI:10.1021/acsnano.1c04496