Engineered peptide PLG0206 overcomes limitations of a challenging antimicrobial drug class

The absence of novel antibiotics for drug-resistant and biofilm-associated infections is a global public health crisis. Antimicrobial peptides explored to address this need have encountered significant development challenges associated with size, toxicity, safety profile, and pharmacokinetics. We de...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2022-09, Vol.17 (9), p.e0274815-e0274815
Main Authors: Huang, David B, Brothers, Kimberly M, Mandell, Jonathan B, Taguchi, Masashi, Alexander, Peter G, Parker, Dana M, Shinabarger, Dean, Pillar, Chris, Morrissey, Ian, Hawser, Stephen, Ghahramani, Parviz, Dobbins, Despina, Pachuda, Nicholas, Montelaro, Ronald, Steckbeck, Jonathan D, Urish, Kenneth L
Format: Article
Language:English
Subjects:
Animal models
Antibiotics
Antiinfectives and antibacterials
Antimicrobial agents
Antimicrobial peptides
Bacterial infections
Biofilms
Biology and Life Sciences
Care and treatment
Clinical isolates
Displays
Drug development
Drug resistance in microorganisms
E coli
Engineering and Technology
Evaluation
Health aspects
Infections
Joint diseases
Medicine and Health Sciences
Multidrug resistance
Mutation
Nosocomial infections
Pathogens
Peptides
Pharmacokinetics
Prostheses
Public health
Public health administration
Research and Analysis Methods
Sheep
Staphylococcus infections
Toxicity
Urinary tract
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The absence of novel antibiotics for drug-resistant and biofilm-associated infections is a global public health crisis. Antimicrobial peptides explored to address this need have encountered significant development challenges associated with size, toxicity, safety profile, and pharmacokinetics. We designed PLG0206, an engineered antimicrobial peptide, to address these limitations. PLG0206 has broad-spectrum activity against >1,200 multidrug-resistant (MDR) ESKAPEE clinical isolates, is rapidly bactericidal, and displays potent anti-biofilm activity against diverse MDR pathogens. PLG0206 displays activity in diverse animal infection models following both systemic (urinary tract infection) and local (prosthetic joint infection) administration. These findings support continuing clinical development of PLG0206 and validate use of rational design for peptide therapeutics to overcome limitations associated with difficult-to-drug pharmaceutical targets.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0274815