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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 M. (2019). Peptidylarginine Deiminase Inhibitors Reduce Bacterial Membrane Vesicle Release and Sensitize Bacteria to Antibiotic Treatment. Frontiers in Cellular and Infection Microbiology, 9, article no. 227.

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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: Journal Item
Copyright Holders: 2019 The Authors
ISSN: 2235-2988
Keywords: outer-membrane vesicles (OMVs); peptidylarginine deiminase (PAD); deimination/citrullination; antibiotic sensitivity; E. coli VCS257; S. aureus subsp. aureus Rosenbach
Academic Unit/School: Faculty of Science, Technology, Engineering and Mathematics (STEM)
Item ID: 62438
Depositing User: ORO Import
Date Deposited: 12 Jul 2019 08:03
Last Modified: 13 Jul 2019 16:36
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