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Effects of LPS Composition in Escherichia coli on Antibacterial Activity and Bacterial Uptake of Antisense Peptide-PNA Conjugates

The physical and chemical properties of the outer membrane of Gram-negative bacteria including Escherichia coli have a significant impact on the antibacterial activity and uptake of antibiotics, including antimicrobial peptides and antisense peptide-peptide nucleic acid (PNA) conjugates. Using a def...

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Autores principales: Goltermann, Lise, Zhang, Meiqin, Ebbensgaard, Anna Elisabeth, Fiodorovaite, Marija, Yavari, Niloofar, Løbner-Olesen, Anders, Nielsen, Peter E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9251361/
https://www.ncbi.nlm.nih.gov/pubmed/35794919
http://dx.doi.org/10.3389/fmicb.2022.877377
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author Goltermann, Lise
Zhang, Meiqin
Ebbensgaard, Anna Elisabeth
Fiodorovaite, Marija
Yavari, Niloofar
Løbner-Olesen, Anders
Nielsen, Peter E.
author_facet Goltermann, Lise
Zhang, Meiqin
Ebbensgaard, Anna Elisabeth
Fiodorovaite, Marija
Yavari, Niloofar
Løbner-Olesen, Anders
Nielsen, Peter E.
author_sort Goltermann, Lise
collection PubMed
description The physical and chemical properties of the outer membrane of Gram-negative bacteria including Escherichia coli have a significant impact on the antibacterial activity and uptake of antibiotics, including antimicrobial peptides and antisense peptide-peptide nucleic acid (PNA) conjugates. Using a defined subset of E. coli lipopolysaccharide (LPS) and envelope mutants, components of the LPS-core, which provide differential susceptibility toward a panel of bacterial penetrating peptide (BPP)-PNA conjugates, were identified. Deleting the outer core of the LPS and perturbing the inner core only sensitized the bacteria toward (KFF)(3)K-PNA conjugates, but not toward conjugates carrying arginine-based BPPs. Interestingly, the chemical composition of the outer LPS core as such, rather than overall hydrophobicity or surface charge, appears to determine the susceptibility to different BPP-PNA conjugates thereby clearly demonstrating the complexity and specificity of the interaction with the LPS/outer membrane. Notably, mutants with outer membrane changes conferring polymyxin resistance did not show resistance toward the BPP-PNA conjugates, thereby eliminating one possible route of resistance for these molecules. Finally, envelope weakening, through deletion of membrane proteins such as OmpA as well as some proteins previously identified as involved in cationic antimicrobial peptide uptake, did not significantly influence BPP-PNA conjugate activity.
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spelling pubmed-92513612022-07-05 Effects of LPS Composition in Escherichia coli on Antibacterial Activity and Bacterial Uptake of Antisense Peptide-PNA Conjugates Goltermann, Lise Zhang, Meiqin Ebbensgaard, Anna Elisabeth Fiodorovaite, Marija Yavari, Niloofar Løbner-Olesen, Anders Nielsen, Peter E. Front Microbiol Microbiology The physical and chemical properties of the outer membrane of Gram-negative bacteria including Escherichia coli have a significant impact on the antibacterial activity and uptake of antibiotics, including antimicrobial peptides and antisense peptide-peptide nucleic acid (PNA) conjugates. Using a defined subset of E. coli lipopolysaccharide (LPS) and envelope mutants, components of the LPS-core, which provide differential susceptibility toward a panel of bacterial penetrating peptide (BPP)-PNA conjugates, were identified. Deleting the outer core of the LPS and perturbing the inner core only sensitized the bacteria toward (KFF)(3)K-PNA conjugates, but not toward conjugates carrying arginine-based BPPs. Interestingly, the chemical composition of the outer LPS core as such, rather than overall hydrophobicity or surface charge, appears to determine the susceptibility to different BPP-PNA conjugates thereby clearly demonstrating the complexity and specificity of the interaction with the LPS/outer membrane. Notably, mutants with outer membrane changes conferring polymyxin resistance did not show resistance toward the BPP-PNA conjugates, thereby eliminating one possible route of resistance for these molecules. Finally, envelope weakening, through deletion of membrane proteins such as OmpA as well as some proteins previously identified as involved in cationic antimicrobial peptide uptake, did not significantly influence BPP-PNA conjugate activity. Frontiers Media S.A. 2022-06-20 /pmc/articles/PMC9251361/ /pubmed/35794919 http://dx.doi.org/10.3389/fmicb.2022.877377 Text en Copyright © 2022 Goltermann, Zhang, Ebbensgaard, Fiodorovaite, Yavari, Løbner-Olesen and Nielsen. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Goltermann, Lise
Zhang, Meiqin
Ebbensgaard, Anna Elisabeth
Fiodorovaite, Marija
Yavari, Niloofar
Løbner-Olesen, Anders
Nielsen, Peter E.
Effects of LPS Composition in Escherichia coli on Antibacterial Activity and Bacterial Uptake of Antisense Peptide-PNA Conjugates
title Effects of LPS Composition in Escherichia coli on Antibacterial Activity and Bacterial Uptake of Antisense Peptide-PNA Conjugates
title_full Effects of LPS Composition in Escherichia coli on Antibacterial Activity and Bacterial Uptake of Antisense Peptide-PNA Conjugates
title_fullStr Effects of LPS Composition in Escherichia coli on Antibacterial Activity and Bacterial Uptake of Antisense Peptide-PNA Conjugates
title_full_unstemmed Effects of LPS Composition in Escherichia coli on Antibacterial Activity and Bacterial Uptake of Antisense Peptide-PNA Conjugates
title_short Effects of LPS Composition in Escherichia coli on Antibacterial Activity and Bacterial Uptake of Antisense Peptide-PNA Conjugates
title_sort effects of lps composition in escherichia coli on antibacterial activity and bacterial uptake of antisense peptide-pna conjugates
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9251361/
https://www.ncbi.nlm.nih.gov/pubmed/35794919
http://dx.doi.org/10.3389/fmicb.2022.877377
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