Simultaneous Antibiofilm and Antiviral Activities of an Engineered Antimicrobial Peptide during Virus-Bacterium Coinfection

ABSTRACT Antimicrobial-resistant infections are an urgent public health threat, and development of novel antimicrobial therapies has been painstakingly slow. Polymicrobial infections are increasingly recognized as a significant source of severe disease and also contribute to reduced susceptibility t...

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Autores principales:	Jeffrey A. Melvin, Lauren P. Lashua, Megan R. Kiedrowski, Guanyi Yang, Berthony Deslouches, Ronald C. Montelaro, Jennifer M. Bomberger
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2016
Materias:	antimicrobial agents antiviral agents biofilms Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/60146e0eeb594e39abdaf580efee2efc
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spelling	oai:doaj.org-article:60146e0eeb594e39abdaf580efee2efc2021-11-15T15:21:18ZSimultaneous Antibiofilm and Antiviral Activities of an Engineered Antimicrobial Peptide during Virus-Bacterium Coinfection10.1128/mSphere.00083-162379-5042https://doaj.org/article/60146e0eeb594e39abdaf580efee2efc2016-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00083-16https://doaj.org/toc/2379-5042ABSTRACT Antimicrobial-resistant infections are an urgent public health threat, and development of novel antimicrobial therapies has been painstakingly slow. Polymicrobial infections are increasingly recognized as a significant source of severe disease and also contribute to reduced susceptibility to antimicrobials. Chronic infections also are characterized by their ability to resist clearance, which is commonly linked to the development of biofilms that are notorious for antimicrobial resistance. The use of engineered cationic antimicrobial peptides (eCAPs) is attractive due to the slow development of resistance to these fast-acting antimicrobials and their ability to kill multidrug-resistant clinical isolates, key elements for the success of novel antimicrobial agents. Here, we tested the ability of an eCAP, WLBU2, to disrupt recalcitrant Pseudomonas aeruginosa biofilms. WLBU2 was capable of significantly reducing biomass and viability of P. aeruginosa biofilms formed on airway epithelium and maintained activity during viral coinfection, a condition that confers extraordinary levels of antibiotic resistance. Biofilm disruption was achieved in short treatment times by permeabilization of bacterial membranes. Additionally, we observed simultaneous reduction of infectivity of the viral pathogen respiratory syncytial virus (RSV). WLBU2 is notable for its ability to maintain activity across a broad range of physiological conditions and showed negligible toxicity toward the airway epithelium, expanding its potential applications as an antimicrobial therapeutic. IMPORTANCE Antimicrobial-resistant infections are an urgent public health threat, making development of novel antimicrobials able to effectively treat these infections extremely important. Chronic and polymicrobial infections further complicate antimicrobial therapy, often through the development of microbial biofilms. Here, we describe the ability of an engineered antimicrobial peptide to disrupt biofilms formed by the ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogen Pseudomonas aeruginosa during coinfection with respiratory syncytial virus. We also observed antiviral activity, indicating the ability of engineered antimicrobial peptides to act as cross-kingdom single-molecule combination therapies.Jeffrey A. MelvinLauren P. LashuaMegan R. KiedrowskiGuanyi YangBerthony DeslouchesRonald C. MontelaroJennifer M. BombergerAmerican Society for Microbiologyarticleantimicrobial agentsantiviral agentsbiofilmsMicrobiologyQR1-502ENmSphere, Vol 1, Iss 3 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	antimicrobial agents antiviral agents biofilms Microbiology QR1-502
spellingShingle	antimicrobial agents antiviral agents biofilms Microbiology QR1-502 Jeffrey A. Melvin Lauren P. Lashua Megan R. Kiedrowski Guanyi Yang Berthony Deslouches Ronald C. Montelaro Jennifer M. Bomberger Simultaneous Antibiofilm and Antiviral Activities of an Engineered Antimicrobial Peptide during Virus-Bacterium Coinfection
description	ABSTRACT Antimicrobial-resistant infections are an urgent public health threat, and development of novel antimicrobial therapies has been painstakingly slow. Polymicrobial infections are increasingly recognized as a significant source of severe disease and also contribute to reduced susceptibility to antimicrobials. Chronic infections also are characterized by their ability to resist clearance, which is commonly linked to the development of biofilms that are notorious for antimicrobial resistance. The use of engineered cationic antimicrobial peptides (eCAPs) is attractive due to the slow development of resistance to these fast-acting antimicrobials and their ability to kill multidrug-resistant clinical isolates, key elements for the success of novel antimicrobial agents. Here, we tested the ability of an eCAP, WLBU2, to disrupt recalcitrant Pseudomonas aeruginosa biofilms. WLBU2 was capable of significantly reducing biomass and viability of P. aeruginosa biofilms formed on airway epithelium and maintained activity during viral coinfection, a condition that confers extraordinary levels of antibiotic resistance. Biofilm disruption was achieved in short treatment times by permeabilization of bacterial membranes. Additionally, we observed simultaneous reduction of infectivity of the viral pathogen respiratory syncytial virus (RSV). WLBU2 is notable for its ability to maintain activity across a broad range of physiological conditions and showed negligible toxicity toward the airway epithelium, expanding its potential applications as an antimicrobial therapeutic. IMPORTANCE Antimicrobial-resistant infections are an urgent public health threat, making development of novel antimicrobials able to effectively treat these infections extremely important. Chronic and polymicrobial infections further complicate antimicrobial therapy, often through the development of microbial biofilms. Here, we describe the ability of an engineered antimicrobial peptide to disrupt biofilms formed by the ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogen Pseudomonas aeruginosa during coinfection with respiratory syncytial virus. We also observed antiviral activity, indicating the ability of engineered antimicrobial peptides to act as cross-kingdom single-molecule combination therapies.
format	article
author	Jeffrey A. Melvin Lauren P. Lashua Megan R. Kiedrowski Guanyi Yang Berthony Deslouches Ronald C. Montelaro Jennifer M. Bomberger
author_facet	Jeffrey A. Melvin Lauren P. Lashua Megan R. Kiedrowski Guanyi Yang Berthony Deslouches Ronald C. Montelaro Jennifer M. Bomberger
author_sort	Jeffrey A. Melvin
title	Simultaneous Antibiofilm and Antiviral Activities of an Engineered Antimicrobial Peptide during Virus-Bacterium Coinfection
title_short	Simultaneous Antibiofilm and Antiviral Activities of an Engineered Antimicrobial Peptide during Virus-Bacterium Coinfection
title_full	Simultaneous Antibiofilm and Antiviral Activities of an Engineered Antimicrobial Peptide during Virus-Bacterium Coinfection
title_fullStr	Simultaneous Antibiofilm and Antiviral Activities of an Engineered Antimicrobial Peptide during Virus-Bacterium Coinfection
title_full_unstemmed	Simultaneous Antibiofilm and Antiviral Activities of an Engineered Antimicrobial Peptide during Virus-Bacterium Coinfection
title_sort	simultaneous antibiofilm and antiviral activities of an engineered antimicrobial peptide during virus-bacterium coinfection
publisher	American Society for Microbiology
publishDate	2016
url	https://doaj.org/article/60146e0eeb594e39abdaf580efee2efc
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Simultaneous Antibiofilm and Antiviral Activities of an Engineered Antimicrobial Peptide during Virus-Bacterium Coinfection

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