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Surface layer proteins from virulent Clostridium difficile ribotypes exhibit signatures of positive selection with consequences for innate immune response.

Surface layer proteins from virulent Clostridium difficile ribotypes exhibit signatures of positive selection with consequences for innate immune response.
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Lynch M, Walsh TA, Marszalowska I, Webb AE, MacAogain M, Rogers TR, Windle H, Kelleher D, O'Connell MJ, Loscher CE,


Lynch M, Walsh TA, Marszalowska I, Webb AE, MacAogain M, Rogers TR, Windle H, Kelleher D, O'Connell MJ, Loscher CE, (click to view)

Lynch M, Walsh TA, Marszalowska I, Webb AE, MacAogain M, Rogers TR, Windle H, Kelleher D, O'Connell MJ, Loscher CE,

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BMC evolutionary biology 2017 03 2317(1) 90 doi 10.1186/s12862-017-0937-8
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.

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