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Peptidylarginine Deiminase Inhibitors Reduce Bacterial Membrane Vesicle Release and Sensitize Bacteria to Antibiotic Treatment

Outer membrane and membrane vesicles (OMV/MV) are released from bacteria and participate in cell communication, biofilm formation and host-pathogen interactions. Peptidylarginine deiminases (PADs) are phylogenetically conserved enzymes that catalyze post-translational deimination/citrullination of p...

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Autores principales: Kosgodage, Uchini S., Matewele, Paul, Mastroianni, Giulia, Kraev, Igor, Brotherton, Dominik, Awamaria, Brigitte, Nicholas, Anthony P., Lange, Sigrun, Inal, Jameel M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6610471/
https://www.ncbi.nlm.nih.gov/pubmed/31316918
http://dx.doi.org/10.3389/fcimb.2019.00227
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author Kosgodage, Uchini S.
Matewele, Paul
Mastroianni, Giulia
Kraev, Igor
Brotherton, Dominik
Awamaria, Brigitte
Nicholas, Anthony P.
Lange, Sigrun
Inal, Jameel M.
author_facet Kosgodage, Uchini S.
Matewele, Paul
Mastroianni, Giulia
Kraev, Igor
Brotherton, Dominik
Awamaria, Brigitte
Nicholas, Anthony P.
Lange, Sigrun
Inal, Jameel M.
author_sort Kosgodage, Uchini S.
collection PubMed
description Outer membrane and membrane vesicles (OMV/MV) are released from bacteria and participate in cell communication, biofilm formation and host-pathogen interactions. Peptidylarginine deiminases (PADs) are phylogenetically conserved enzymes that catalyze post-translational deimination/citrullination of proteins, causing structural and functional changes in target proteins. PADs also play major roles in the regulation of eukaryotic extracellular vesicle release. Here we show phylogenetically conserved pathways of PAD-mediated OMV/MV release in bacteria and describe deiminated/citrullinated proteins in E. coli and their derived OMV/MVs. Furthermore, we show that PAD inhibitors can be used to effectively reduce OMV/MV release, both in Gram-negative and Gram-positive bacteria. Importantly, this resulted in enhanced antibiotic sensitivity of both E. coli and S. aureus to a range of antibiotics tested. Our findings reveal novel strategies for applying pharmacological OMV/MV-inhibition to reduce antibiotic resistance.
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spelling pubmed-66104712019-07-17 Peptidylarginine Deiminase Inhibitors Reduce Bacterial Membrane Vesicle Release and Sensitize Bacteria to Antibiotic Treatment Kosgodage, Uchini S. Matewele, Paul Mastroianni, Giulia Kraev, Igor Brotherton, Dominik Awamaria, Brigitte Nicholas, Anthony P. Lange, Sigrun Inal, Jameel M. Front Cell Infect Microbiol Cellular and Infection Microbiology Outer membrane and membrane vesicles (OMV/MV) are released from bacteria and participate in cell communication, biofilm formation and host-pathogen interactions. Peptidylarginine deiminases (PADs) are phylogenetically conserved enzymes that catalyze post-translational deimination/citrullination of proteins, causing structural and functional changes in target proteins. PADs also play major roles in the regulation of eukaryotic extracellular vesicle release. Here we show phylogenetically conserved pathways of PAD-mediated OMV/MV release in bacteria and describe deiminated/citrullinated proteins in E. coli and their derived OMV/MVs. Furthermore, we show that PAD inhibitors can be used to effectively reduce OMV/MV release, both in Gram-negative and Gram-positive bacteria. Importantly, this resulted in enhanced antibiotic sensitivity of both E. coli and S. aureus to a range of antibiotics tested. Our findings reveal novel strategies for applying pharmacological OMV/MV-inhibition to reduce antibiotic resistance. Frontiers Media S.A. 2019-06-27 /pmc/articles/PMC6610471/ /pubmed/31316918 http://dx.doi.org/10.3389/fcimb.2019.00227 Text en Copyright © 2019 Kosgodage, Matewele, Mastroianni, Kraev, Brotherton, Awamaria, Nicholas, Lange and Inal. http://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 Cellular and Infection Microbiology
Kosgodage, Uchini S.
Matewele, Paul
Mastroianni, Giulia
Kraev, Igor
Brotherton, Dominik
Awamaria, Brigitte
Nicholas, Anthony P.
Lange, Sigrun
Inal, Jameel M.
Peptidylarginine Deiminase Inhibitors Reduce Bacterial Membrane Vesicle Release and Sensitize Bacteria to Antibiotic Treatment
title Peptidylarginine Deiminase Inhibitors Reduce Bacterial Membrane Vesicle Release and Sensitize Bacteria to Antibiotic Treatment
title_full Peptidylarginine Deiminase Inhibitors Reduce Bacterial Membrane Vesicle Release and Sensitize Bacteria to Antibiotic Treatment
title_fullStr Peptidylarginine Deiminase Inhibitors Reduce Bacterial Membrane Vesicle Release and Sensitize Bacteria to Antibiotic Treatment
title_full_unstemmed Peptidylarginine Deiminase Inhibitors Reduce Bacterial Membrane Vesicle Release and Sensitize Bacteria to Antibiotic Treatment
title_short Peptidylarginine Deiminase Inhibitors Reduce Bacterial Membrane Vesicle Release and Sensitize Bacteria to Antibiotic Treatment
title_sort peptidylarginine deiminase inhibitors reduce bacterial membrane vesicle release and sensitize bacteria to antibiotic treatment
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6610471/
https://www.ncbi.nlm.nih.gov/pubmed/31316918
http://dx.doi.org/10.3389/fcimb.2019.00227
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