University of Hertfordshire

Documents

  • Uchini S Kosgodage
  • Paul Matewele
  • Giulia Mastroianni
  • Sigrun Lange
  • Igor Kraev
  • Dominik Brotherton
  • Brigitte Awamaria
  • Anthony P. Nicholas
  • Jameel Inal
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Original languageEnglish
JournalFrontiers Cellular and Infection Microbiology
Journal publication date11 Jun 2019
Publication statusAccepted/In press - 11 Jun 2019

Abstract

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 catalyse 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
28 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.

ID: 16946714