Ferric quinate (QPLEX) interacts with the major outer membrane protein (MOMP) of Campylobacter jejuni and enters through the porin channel into the periplasmic space
Ferric chelates like ferric tyrosinate (TYPLEX) and the closely related ferric quinate (QPLEX) are structural mimics of bacterial siderophores. TYPLEX has been trialled as a feed additive in farming of commercial broilers, reducing Campylobacter loads by 2–3 log10 and leading to faster growth and be...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-01-01
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| Series: | Computational and Structural Biotechnology Journal |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2001037022004378 |
| _version_ | 1797978188589039616 |
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| author | Jennifer C. Okoye Jeddidiah Bellamy-Carter Neil J. Oldham Neil J. Oldfield Jafar Mahdavi Panos Soultanas |
| author_facet | Jennifer C. Okoye Jeddidiah Bellamy-Carter Neil J. Oldham Neil J. Oldfield Jafar Mahdavi Panos Soultanas |
| author_sort | Jennifer C. Okoye |
| collection | DOAJ |
| description | Ferric chelates like ferric tyrosinate (TYPLEX) and the closely related ferric quinate (QPLEX) are structural mimics of bacterial siderophores. TYPLEX has been trialled as a feed additive in farming of commercial broilers, reducing Campylobacter loads by 2–3 log10 and leading to faster growth and better feed consumption. These ferric chelates offer a good alternative feed additive to antibiotics helping to reduce the indiscriminate use of preventative antibiotics in broiler farming to control Campylobacter infections. In this study, we show that QPLEX binds to the Major Outer Membrane Protein (MOMP) of C. jejuni NCTC11168. MOMP is an essential and abundant outer membrane porin on the surface of the bacteria, acting as an adhesin to help establish infection by mediating attachment of C. jejuni onto the gut epithelium of broilers and establish infection. Using carbene footprinting, we map the MOMP-QPLEX interaction and show by complementary in silico docking that QPLEX enters the porin channel through interactions at the extracellular face, translocates down the channel through a dipole transverse electric field towards the opposite end and is released into the periplasm at the intracellular face of MOMP. Our studies suggest a potential mechanism for the non-antibiotic anti-Campylobacter activity of these ferric chelates. |
| first_indexed | 2024-04-11T05:19:00Z |
| format | Article |
| id | doaj.art-eda1545e797f40e4bb545821f72409a0 |
| institution | Directory Open Access Journal |
| issn | 2001-0370 |
| language | English |
| last_indexed | 2024-04-11T05:19:00Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Computational and Structural Biotechnology Journal |
| spelling | doaj.art-eda1545e797f40e4bb545821f72409a02022-12-24T04:54:35ZengElsevierComputational and Structural Biotechnology Journal2001-03702022-01-012053555363Ferric quinate (QPLEX) interacts with the major outer membrane protein (MOMP) of Campylobacter jejuni and enters through the porin channel into the periplasmic spaceJennifer C. Okoye0Jeddidiah Bellamy-Carter1Neil J. Oldham2Neil J. Oldfield3Jafar Mahdavi4Panos Soultanas5School of Chemistry, Biodiscovery Institute, University of Nottingham, University Park NG7 2RD, United KingdomSchool of Chemistry, University of Nottingham, University Park NG7 2RD, United KingdomSchool of Chemistry, University of Nottingham, University Park NG7 2RD, United KingdomSchool of Life Sciences, University of Nottingham, University Park NG7 2RD, United KingdomSchool of Chemistry, Biodiscovery Institute, University of Nottingham, University Park NG7 2RD, United KingdomSchool of Chemistry, Biodiscovery Institute, University of Nottingham, University Park NG7 2RD, United Kingdom; Corresponding author.Ferric chelates like ferric tyrosinate (TYPLEX) and the closely related ferric quinate (QPLEX) are structural mimics of bacterial siderophores. TYPLEX has been trialled as a feed additive in farming of commercial broilers, reducing Campylobacter loads by 2–3 log10 and leading to faster growth and better feed consumption. These ferric chelates offer a good alternative feed additive to antibiotics helping to reduce the indiscriminate use of preventative antibiotics in broiler farming to control Campylobacter infections. In this study, we show that QPLEX binds to the Major Outer Membrane Protein (MOMP) of C. jejuni NCTC11168. MOMP is an essential and abundant outer membrane porin on the surface of the bacteria, acting as an adhesin to help establish infection by mediating attachment of C. jejuni onto the gut epithelium of broilers and establish infection. Using carbene footprinting, we map the MOMP-QPLEX interaction and show by complementary in silico docking that QPLEX enters the porin channel through interactions at the extracellular face, translocates down the channel through a dipole transverse electric field towards the opposite end and is released into the periplasm at the intracellular face of MOMP. Our studies suggest a potential mechanism for the non-antibiotic anti-Campylobacter activity of these ferric chelates.http://www.sciencedirect.com/science/article/pii/S2001037022004378 |
| spellingShingle | Jennifer C. Okoye Jeddidiah Bellamy-Carter Neil J. Oldham Neil J. Oldfield Jafar Mahdavi Panos Soultanas Ferric quinate (QPLEX) interacts with the major outer membrane protein (MOMP) of Campylobacter jejuni and enters through the porin channel into the periplasmic space Computational and Structural Biotechnology Journal |
| title | Ferric quinate (QPLEX) interacts with the major outer membrane protein (MOMP) of Campylobacter jejuni and enters through the porin channel into the periplasmic space |
| title_full | Ferric quinate (QPLEX) interacts with the major outer membrane protein (MOMP) of Campylobacter jejuni and enters through the porin channel into the periplasmic space |
| title_fullStr | Ferric quinate (QPLEX) interacts with the major outer membrane protein (MOMP) of Campylobacter jejuni and enters through the porin channel into the periplasmic space |
| title_full_unstemmed | Ferric quinate (QPLEX) interacts with the major outer membrane protein (MOMP) of Campylobacter jejuni and enters through the porin channel into the periplasmic space |
| title_short | Ferric quinate (QPLEX) interacts with the major outer membrane protein (MOMP) of Campylobacter jejuni and enters through the porin channel into the periplasmic space |
| title_sort | ferric quinate qplex interacts with the major outer membrane protein momp of campylobacter jejuni and enters through the porin channel into the periplasmic space |
| url | http://www.sciencedirect.com/science/article/pii/S2001037022004378 |
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