Ferric quinate (QPLEX) interacts with the major outer membrane protein (MOMP) of Campylobacter jejuni and enters through the porin channel into the periplasmic space

Okoye, Jennifer C.; Bellamy-Carter, Jeddidiah; Oldham, Neil J.; Oldfield, Neil J.; Mahdavi, Jafar; Soultanas, Panos

Abstract

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.

Citation

Okoye, J. C., Bellamy-Carter, J., Oldham, N. J., Oldfield, N. J., Mahdavi, J., & Soultanas, P. (2022). 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, 20, 5355-5363. https://doi.org/10.1016/j.csbj.2022.09.032

• Journal Article Type: Article
• Acceptance Date: Sep 21, 2022
• Online Publication Date: Sep 24, 2022
• Publication Date: 2022-09
• Deposit Date: Sep 26, 2022
• Publicly Available Date: Oct 4, 2022
• Journal: Computational and Structural Biotechnology Journal
• Electronic ISSN: 2001-0370
• Publisher: Elsevier BV
• Peer Reviewed: Peer Reviewed
• Volume: 20
• Pages: 5355-5363
• DOI: https://doi.org/10.1016/j.csbj.2022.09.032
• Keywords: Computer Science Applications; Genetics; Biochemistry; Structural Biology; Biophysics; Biotechnology
• Public URL: https://nottingham-repository.worktribe.com/output/11744427
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S2001037022004378?via%3Dihub