Elmi, A;
Dorey, A;
Watson, E;
Jagatia, H;
Inglis, NF;
Gundogdu, O;
Bajaj-Elliott, M;
... Dorrell, N; + view all
(2018)
The bile salt sodium taurocholate induces Campylobacter jejuni outer membrane vesicle production and increases OMV-associated proteolytic activity.
Cellular Microbiology
, 20
(3)
, Article e12814. 10.1111/cmi.12814.
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Abstract
Campylobacter jejuni, the leading cause of bacterial acute gastroenteritis worldwide, secretes an arsenal of virulence‐associated proteins within outer membrane vesicles (OMVs). C. jejuni OMVs contain three serine proteases (HtrA, Cj0511, and Cj1365c) that cleave the intestinal epithelial cell (IEC) tight and adherens junction proteins occludin and E‐cadherin, promoting enhanced C. jejuni adhesion to and invasion of IECs. C. jejuni OMVs also induce IECs innate immune responses. The bile salt sodium taurocholate (ST) is sensed as a host signal to coordinate the activation of virulence‐associated genes in the enteric pathogen Vibrio cholerae. In this study, the effect of ST on C. jejuni OMVs was investigated. Physiological concentrations of ST do not have an inhibitory effect on C. jejuni growth until the early stationary phase. Coculture of C. jejuni with 0.1% or 0.2% (w/v) ST stimulates OMV production, increasing both lipid and protein concentrations. C. jejuni ST‐OMVs possess increased proteolytic activity and exhibit a different protein profile compared to OMVs isolated in the absence of ST. ST‐OMVs exhibit enhanced cytotoxicity and immunogenicity to T84 IECs and enhanced killing of Galleria mellonella larvae. ST increases the level of mRNA transcripts of the OMVs‐associated serine protease genes and the cdtABC operon that encodes the cytolethal distending toxin. Coculture with ST significantly enhances the OMVs‐induced cleavage of E‐cadherin and occludin. C. jejuni OMVs also cleave the major endoplasmic reticulum chaperone protein BiP/GRP78 and this activity is associated with the Cj1365c protease. These data suggest that C. jejuni responds to the presence of physiological concentrations of the bile salt ST that increases OMV production and the synthesis of virulence‐associated factors that are secreted within the OMVs. We propose that these events contribute to pathogenesis.
| Type: | Article |
|---|---|
| Title: | The bile salt sodium taurocholate induces Campylobacter jejuni outer membrane vesicle production and increases OMV-associated proteolytic activity |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1111/cmi.12814 |
| Publisher version: | https://doi.org/10.1111/cmi.12814 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Cell Biology, Microbiology, bile salts, Campylobacter, outer membrane vesicles, proteolytic activity, CYTOLETHAL DISTENDING TOXIN, GRAM-NEGATIVE BACTERIA, HUMAN EPITHELIAL-CELLS, ESCHERICHIA-COLI, TIGHT JUNCTIONS, STRESS-RESPONSE, SUBTILASE CYTOTOXIN, MASS-SPECTROMETRY, BIOFILM FORMATION, BARRIER FUNCTION |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10069262 |
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