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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Cell. Infect. Microbiol. | doi: 10.3389/fcimb.2019.00177

Sodium taurocholate stimulates Campylobacter jejuni outer membrane vesicle production via down-regulation of the maintenance of lipid asymmetry pathway

  • 1London School of Hygiene and Tropical Medicine (LSHTM), United Kingdom
  • 2University of Sheffield, United Kingdom
  • 3Nottingham Trent University, United Kingdom
  • 4Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine (LSHTM), United Kingdom

Campylobacter jejuni outer membrane vesicles (OMVs) contain numerous virulence-associated proteins including the cytolethal distending toxin and three serine proteases. As C. jejuni lacks the classical virulence-associated secretion systems of other enteric pathogens that deliver effectors directly into target cells, OMVs may have a particularly important role in virulence. C. jejuni OMV production is stimulated by the presence of physiological concentrations of the bile salt sodium taurocholate (ST) through an unknown mechanism. The maintenance of lipid asymmetry (MLA) pathway has been implicated in a novel mechanism for OMV biogenesis, open to regulation by host signals. In this study we investigated the role of the MLA pathway in C. jejuni OMV biogenesis with ST as a potential regulator. OMV production was quantified by analysing protein and lipid concentrations of OMV preparations and OMV particle counts produced by nanoparticle tracking analysis. Mutation of mlaA which encodes the outer membrane component of the MLA pathway significantly increased OMV production compared to the wild-type strain. Detergent sensitivity and membrane permeability assays confirmed the increased OMV production was not due to changes in membrane stability. The presence of 0.2% (w/v) ST increased wild-type OMV production and reduced OMV size, but did not further stimulate mlaA mutant OMV production or significantly alter mlaA mutant OMV size. qRT-PCR analysis demonstrated that the presence of ST decreased expression of both mlaA and mlaC in C. jejuni wild-type strains 11168 and 488. Collectively the data in this study suggests C. jejuni can regulate OMV production in response to host gut signals through changes in expression of the MLA pathway. As the gut bile composition is dependent on both diet and the microbiota, this study highlights the potential importance of diet and lifestyle factors on the varying disease presentations associated with gut pathogen infection.

Keywords: Campylobacter, Bile salt, Outer membrane vesicle (OMV), MLAA, Maintainance of lipid asymmetry pathway

Received: 19 Feb 2019; Accepted: 09 May 2019.

Edited by:

D Scott Merrell, Department of Microbiology and Immunology, Uniformed Services University, United States

Reviewed by:

Ramesh Vemulapalli, Texas A&M University, United States
Philip R. Hardwidge, Kansas State University, United States  

Copyright: © 2019 Davies, Taylor, Elmi, Winter, Liaw, Grabowska, Gundogdu, Wren, Kelly and Dorrell. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Nick Dorrell, London School of Hygiene and Tropical Medicine (LSHTM), Pathogen Molecular Biology, London, WC1E 7HT, United Kingdom, nick.dorrell@lshtm.ac.uk