Lynch, M, Walsh, TA, Marszalowska, I et al. (7 more authors) (2017) Surface Layer Proteins from virulent Clostridium difficile ribotypes exhibit signatures of positive selection with consequences for innate immune response. BMC Evolutionary Biology, 17 (1). 90. ISSN 1471-2148
Abstract
Background: Clostridium difficile is a nosocomial pathogen prevalent in hospitals worldwide and increasingly common in the community. Sequence differences have been shown to be present in the Surface Layer Proteins (SLPs) from different C. difficile ribotypes (RT) however whether these differences influence severity of infection is still not clear. Results: We used a molecular evolutionary approach to analyse SLPs from twenty-six C. difficile RTs representing different slpA sequences. We demonstrate that SLPs from RT 027 and 078 exhibit evidence of positive selection (PS). We compared the effect of these SLPs to those purified from RT 001 and 014, which did not exhibit PS, and demonstrate that the presence of sites under positive selection correlates with ability to activate macrophages. SLPs from RTs 027 and 078 induced a more potent response in macrophages, with increased levels of IL-6, IL-12p40, IL-10, MIP-1α, MIP-2 production relative to RT 001 and 014. Furthermore, RTs 027 and 078 induced higher expression of CD40, CD80 and MHC II on macrophages with decreased ability to phagocytose relative to LPS. Conclusions: These results tightly link sequence differences in C. difficile SLPs to disease susceptibility and severity, and suggest that positively selected sites in the SLPs may play a role in driving the emergence of hyper-virulent strains.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | (c) 2017, The Author(s). This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
Keywords: | Clostridium difficile; Surface Layer Protein; positive selection; protein functional shift; protein evolution; virulence |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 22 Mar 2017 10:59 |
Last Modified: | 23 Jun 2023 22:25 |
Status: | Published |
Publisher: | BioMed Central |
Identification Number: | 10.1186/s12862-017-0937-8 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:113974 |
Commentary/Response Threads
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Lynch, M, Walsh, TA, Marszalowska, I, Webb, AE, MacAogain, M, Rogers, TR, Windle, H, Kelleher, D, O'Connell, MJ and Loscher, CE
Surface Layer Proteins from virulent Clostridium difficile ribotypes exhibit signatures of positive selection with consequences for innate immune response. (deposited 22 Mar 2017 10:59)
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- Lynch, M, Walsh, TA, Marszalowska, I, Webb, AE, Mac Aogáin, M, Rogers, TR, Windle, H, Kelleher, D, O’Connell, MJ and Loscher, CE Erratum to: Surface layer proteins from virulent Clostridium difficile ribotypes exhibit signatures of positive selection with consequences for innate immune response. (deposited 10 Aug 2017 14:23)