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 and Inal, Jameel (2019) Peptidylarginine deiminase inhibitors reduce bacterial membrane vesicle release and sensitize bacteria to antibiotic treatment. Frontiers in Cellular and Infection Microbiology, 9. pp. 227-244. ISSN 2235-2988

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Abstract / 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.

Item Type:	Article
Additional Information:	** From Frontiers via Jisc Publications Router
Uncontrolled Keywords:	cellular and infection microbiology, outer-membrane vesicles (OMVs), peptidylarginine deiminase (PAD), deimination/citrullination, antibiotic sensitivity, E. coli VCS257, S. aureus subsp. aureus Rosenbach
Subjects:	500 Natural Sciences and Mathematics > 570 Life sciences; biology
Department:	School of Human Sciences
SWORD Depositor:	Pub Router
Depositing User:	Pub Router
Date Deposited:	12 Jul 2019 08:48
Last Modified:	18 Mar 2020 11:19
URI:	https://repository.londonmet.ac.uk/id/eprint/4974

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