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

Autor: Dominik Brotherton, Giulia Mastroianni, Igor Kraev, Brigitte Awamaria, Sigrun Lange, Paul Matewele, Jameel M. Inal, Anthony P. Nicholas, Uchini S. Kosgodage
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Microbiology (medical)
Staphylococcus aureus
medicine.drug_class
outer-membrane vesicles (OMVs)
Antibiotic sensitivity
030106 microbiology
Immunology
Antibiotics
lcsh:QR1-502
Microbial Sensitivity Tests
Microbiology
peptidylarginine deiminase (PAD)
lcsh:Microbiology
deimination/citrullination
03 medical and health sciences
Extracellular Vesicles
Cellular and Infection Microbiology
Bacterial Proteins
S. aureus subsp. aureus Rosenbach
medicine
Escherichia coli
Enzyme Inhibitors
dewey570
Original Research
chemistry.chemical_classification
Membranes
Microbial Viability
biology
Bacteria
Biofilm
Citrullination
Extracellular vesicle
biology.organism_classification
E. coli VCS257
antibiotic sensitivity
Cell biology
Anti-Bacterial Agents
030104 developmental biology
Infectious Diseases
Enzyme
chemistry
Host-Pathogen Interactions
Protein-Arginine Deiminases
Nanoparticles
Bacterial outer membrane
Protein Processing
Post-Translational
Zdroj: Frontiers in Cellular and Infection Microbiology, Vol 9 (2019)
Frontiers in Cellular and Infection Microbiology
ISSN: 2235-2988
DOI: 10.3389/fcimb.2019.00227/full
Popis: 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.
Databáze: OpenAIRE
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