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...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2019
|
| Subjects: | |
| Online Access: | https://repository.londonmet.ac.uk/4974/1/fcimb-09-00227.pdf |
| _version_ | 1804072399516205056 |
|---|---|
| author | Kosgodage, Uchini S. Matewele, Paul Mastroianni, Giulia Kraev, Igor Brotherton, Dominik Awamaria, Brigitte Nicholas, Anthony P. Lange, Sigrun Inal, Jameel |
| author_facet | Kosgodage, Uchini S. Matewele, Paul Mastroianni, Giulia Kraev, Igor Brotherton, Dominik Awamaria, Brigitte Nicholas, Anthony P. Lange, Sigrun Inal, Jameel |
| author_sort | Kosgodage, Uchini S. |
| collection | LMU |
| 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. |
| first_indexed | 2024-07-09T03:58:32Z |
| format | Article |
| id | oai:repository.londonmet.ac.uk:4974 |
| institution | London Metropolitan University |
| language | English |
| last_indexed | 2024-07-09T03:58:32Z |
| publishDate | 2019 |
| publisher | Frontiers Media S.A. |
| record_format | eprints |
| spelling | oai:repository.londonmet.ac.uk:49742023-05-23T11:37:50Z http://repository.londonmet.ac.uk/4974/ 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 570 Life sciences; biology 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 Article PeerReviewed text en cc_by_nc_nd_4 https://repository.londonmet.ac.uk/4974/1/fcimb-09-00227.pdf 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 10.3389/fcimb.2019.00227 |
| spellingShingle | 570 Life sciences; biology Kosgodage, Uchini S. Matewele, Paul Mastroianni, Giulia Kraev, Igor Brotherton, Dominik Awamaria, Brigitte Nicholas, Anthony P. Lange, Sigrun Inal, Jameel 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 | 570 Life sciences; biology |
| url | https://repository.londonmet.ac.uk/4974/1/fcimb-09-00227.pdf |
| work_keys_str_mv | AT kosgodageuchinis peptidylargininedeiminaseinhibitorsreducebacterialmembranevesiclereleaseandsensitizebacteriatoantibiotictreatment AT matewelepaul peptidylargininedeiminaseinhibitorsreducebacterialmembranevesiclereleaseandsensitizebacteriatoantibiotictreatment AT mastroiannigiulia peptidylargininedeiminaseinhibitorsreducebacterialmembranevesiclereleaseandsensitizebacteriatoantibiotictreatment AT kraevigor peptidylargininedeiminaseinhibitorsreducebacterialmembranevesiclereleaseandsensitizebacteriatoantibiotictreatment AT brothertondominik peptidylargininedeiminaseinhibitorsreducebacterialmembranevesiclereleaseandsensitizebacteriatoantibiotictreatment AT awamariabrigitte peptidylargininedeiminaseinhibitorsreducebacterialmembranevesiclereleaseandsensitizebacteriatoantibiotictreatment AT nicholasanthonyp peptidylargininedeiminaseinhibitorsreducebacterialmembranevesiclereleaseandsensitizebacteriatoantibiotictreatment AT langesigrun peptidylargininedeiminaseinhibitorsreducebacterialmembranevesiclereleaseandsensitizebacteriatoantibiotictreatment AT inaljameel peptidylargininedeiminaseinhibitorsreducebacterialmembranevesiclereleaseandsensitizebacteriatoantibiotictreatment |