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The antibiotic vancomycin induces complexation and aggregation of gastrointestinal and submaxillary mucins

Dinu, Vlad; Lu, Yudong; Weston, Nicola; Lithgo, Ryan; Coupe, Hayley; Channell, Guy; Adams, Gary G; Torcello Gómez, Amelia; Sabater Sanchez, Carlos; Mackie, Alan; Parmenter, Christopher; Fisk, Ian; Phillips-Jones, Mary K.; Harding, Stephen E.

Authors

Vlad Dinu

Yudong Lu

Nicola Weston

Ryan Lithgo

Hayley Coupe

Guy Channell

Gary G Adams

Amelia Torcello Gómez

Carlos Sabater Sanchez

Alan Mackie

Christopher Parmenter

Ian Fisk

Stephen E. Harding steve.harding@nottingham.ac.uk



Abstract

© 2020, The Author(s). Vancomycin, a branched tricyclic glycosylated peptide antibiotic, is a last-line defence against serious infections caused by staphylococci, enterococci and other Gram-positive bacteria. Orally-administered vancomycin is the drug of choice to treat pseudomembranous enterocolitis in the gastrointestinal tract. However, the risk of vancomycin-resistant enterococcal infection or colonization is significantly associated with oral vancomycin. Using the powerful matrix-free assay of co-sedimentation analytical ultracentrifugation, reinforced by dynamic light scattering and environmental scanning electron microscopy, and with porcine mucin as the model mucin system, this is the first study to demonstrate strong interactions between vancomycin and gastric and intestinal mucins, resulting in very large aggregates and depletion of macromolecular mucin and occurring at concentrations relevant to oral dosing. In the case of another mucin which has a much lower degree of glycosylation (~60%) – bovine submaxillary mucin - a weaker but still demonstrable interaction is observed. Our demonstration - for the first time - of complexation/depletion interactions for model mucin systems with vancomycin provides the basis for further study on the implications of complexation on glycopeptide transit in humans, antibiotic bioavailability for target inhibition, in situ generation of resistance and future development strategies for absorption of the antibiotic across the mucus barrier.

Journal Article Type Article
Publication Date Jan 22, 2020
Journal Scientific Reports
Print ISSN 2045-2322
Electronic ISSN 2045-2322
Publisher Nature Publishing Group
Peer Reviewed Peer Reviewed
Volume 10
Issue 1
Article Number 960
APA6 Citation Dinu, V., Lu, Y., Weston, N., Lithgo, R., Coupe, H., Channell, G., …Harding, S. E. (2020). The antibiotic vancomycin induces complexation and aggregation of gastrointestinal and submaxillary mucins. Scientific Reports, 10(1), https://doi.org/10.1038/s41598-020-57776-3
DOI https://doi.org/10.1038/s41598-020-57776-3
Keywords Multidisciplinary
Publisher URL https://www.nature.com/articles/s41598-020-57776-3
Additional Information Received: 29 May 2018; Accepted: 19 December 2019; First Online: 22 January 2020; : The authors declare no competing interests.

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