Ferric quinate (QPLEX) inhibits the interaction of major outer membrane protein (MOMP) with the Lewis b (Leb) antigen and limits Campylobacter colonization in broilers

Jennifer C. Okoye; Alexandria Holland; Matthaios Pitoulias; Vasileios Paschalis; Artem Piddubnyi; Osman A. Dufailu; Thomas Borén; Neil J. Oldfield; Jafar Mahdavi; Panos Soultanas

doi:10.3389/fmicb.2023.1146418

Ferric quinate (QPLEX) inhibits the interaction of major outer membrane protein (MOMP) with the Lewis b (Leb) antigen and limits Campylobacter colonization in broilers

Jennifer C. Okoye, Alexandria Holland, Matthaios Pitoulias, Vasileios Paschalis, Artem Piddubnyi, Osman A. Dufailu, Thomas Borén, Neil J. Oldfield, Jafar Mahdavi, Panos Soultanas

Department of Life Sciences

Research output: Contribution to journal › Article › peer-review

1 Citation (SciVal)

Abstract

Campylobacter jejuni colonizes hosts by interacting with Blood Group Antigens (BgAgs) on the surface of gastrointestinal epithelia. Genetic variations in BgAg expression affects host susceptibility to C. jejuni. Here, we show that the essential major outer membrane protein (MOMP) of C. jejuni NCTC11168 binds to the Lewis b (Leb) antigen on the gastrointestinal epithelia of host tissues and this interaction can be competitively inhibited by ferric quinate (QPLEX), a ferric chelate structurally similar to bacterial siderophores. We provide evidence that QPLEX competitively inhibits the MOMP-Leb interaction. Furthermore, we demonstrate that QPLEX can be used as a feed additive in broiler farming to significantly reduce C. jejuni colonization. Our results indicate that QPLEX can be a viable alternative to the preventative use of antibiotics in broiler farming to combat C. jejuni infections.

Original language	English
Article number	1146418
Number of pages	12
Journal	Frontiers in Microbiology
Volume	14
Early online date	10 Mar 2023
DOIs	https://doi.org/10.3389/fmicb.2023.1146418
Publication status	Published - 10 Mar 2023

Data Availability Statement

The original contributions presented in this study are included in the article/Supplementary material, further inquiries can be directed to the corresponding authors.

Acknowledgements

We thank the administrative and technical staff in the School of
Chemistry, University of Nottingham for invaluable basic support,
Dr. Tim Self and Dr. Robert Marcus from the SLIM (School of
Life Sciences Imaging) team at the University of Nottingham for
help with our imaging studies, Dr. Anne Knox from the Roslin
Institute and Dr. Elinor McCartney Technical director of Pen and
Tec Consulting for advice regarding the broiler trial at the Roslin
Institute, and Akeso Biomedical Inc., for funding the broiler trial at
the Roslin Institute.

Funding

Research in the P.S. Lab was supported by the BBSRC (Grant Number: BB/R013357/1). JCO was supported 50% by an EPSRC Centre for Doctoral Training grant in Sustainable Chemistry (EP/L015633/1) and 50% by Akeso Biomedical Inc., The study carried out at the Roslin Institute was funded by Akeso Biomedical Inc., Akeso Biomedical Inc., had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Cite this

Okoye, J. C., Holland, A., Pitoulias, M., Paschalis, V., Piddubnyi, A., Dufailu, O. A., Borén, T., Oldfield, N. J., Mahdavi, J., & Soultanas, P. (2023). Ferric quinate (QPLEX) inhibits the interaction of major outer membrane protein (MOMP) with the Lewis b (Leb) antigen and limits Campylobacter colonization in broilers. Frontiers in Microbiology, 14, Article 1146418. https://doi.org/10.3389/fmicb.2023.1146418

Okoye, JC, Holland, A, Pitoulias, M, Paschalis, V, Piddubnyi, A, Dufailu, OA, Borén, T, Oldfield, NJ, Mahdavi, J & Soultanas, P 2023, 'Ferric quinate (QPLEX) inhibits the interaction of major outer membrane protein (MOMP) with the Lewis b (Leb) antigen and limits Campylobacter colonization in broilers', Frontiers in Microbiology, vol. 14, 1146418. https://doi.org/10.3389/fmicb.2023.1146418

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title = "Ferric quinate (QPLEX) inhibits the interaction of major outer membrane protein (MOMP) with the Lewis b (Leb) antigen and limits Campylobacter colonization in broilers",

abstract = "Campylobacter jejuni colonizes hosts by interacting with Blood Group Antigens (BgAgs) on the surface of gastrointestinal epithelia. Genetic variations in BgAg expression affects host susceptibility to C. jejuni. Here, we show that the essential major outer membrane protein (MOMP) of C. jejuni NCTC11168 binds to the Lewis b (Leb) antigen on the gastrointestinal epithelia of host tissues and this interaction can be competitively inhibited by ferric quinate (QPLEX), a ferric chelate structurally similar to bacterial siderophores. We provide evidence that QPLEX competitively inhibits the MOMP-Leb interaction. Furthermore, we demonstrate that QPLEX can be used as a feed additive in broiler farming to significantly reduce C. jejuni colonization. Our results indicate that QPLEX can be a viable alternative to the preventative use of antibiotics in broiler farming to combat C. jejuni infections.",

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AU - Okoye, Jennifer C.

AU - Holland, Alexandria

AU - Pitoulias, Matthaios

AU - Paschalis, Vasileios

AU - Piddubnyi, Artem

AU - Dufailu, Osman A.

AU - Borén, Thomas

AU - Oldfield, Neil J.

AU - Mahdavi, Jafar

AU - Soultanas, Panos

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AB - Campylobacter jejuni colonizes hosts by interacting with Blood Group Antigens (BgAgs) on the surface of gastrointestinal epithelia. Genetic variations in BgAg expression affects host susceptibility to C. jejuni. Here, we show that the essential major outer membrane protein (MOMP) of C. jejuni NCTC11168 binds to the Lewis b (Leb) antigen on the gastrointestinal epithelia of host tissues and this interaction can be competitively inhibited by ferric quinate (QPLEX), a ferric chelate structurally similar to bacterial siderophores. We provide evidence that QPLEX competitively inhibits the MOMP-Leb interaction. Furthermore, we demonstrate that QPLEX can be used as a feed additive in broiler farming to significantly reduce C. jejuni colonization. Our results indicate that QPLEX can be a viable alternative to the preventative use of antibiotics in broiler farming to combat C. jejuni infections.

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DO - 10.3389/fmicb.2023.1146418

M3 - Article

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JO - Frontiers in Microbiology

JF - Frontiers in Microbiology

M1 - 1146418

ER -

Ferric quinate (QPLEX) inhibits the interaction of major outer membrane protein (MOMP) with the Lewis b (Leb) antigen and limits Campylobacter colonization in broilers

Abstract

Data Availability Statement

Acknowledgements

Funding

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