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...

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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
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cited_by cdi_FETCH-LOGICAL-c669t-f37f1ed81284568fc9a953dad743c5eb5c344b331fa3c65728decca63a8db8773
cites cdi_FETCH-LOGICAL-c669t-f37f1ed81284568fc9a953dad743c5eb5c344b331fa3c65728decca63a8db8773
container_end_page e0274815
container_issue 9
container_start_page e0274815
container_title PloS one
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creator 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
description 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.
doi_str_mv 10.1371/journal.pone.0274815
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1932-6203
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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
title Engineered peptide PLG0206 overcomes limitations of a challenging antimicrobial drug class
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