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Type: Journal article
Title: A random six-phase switch regulates pneumococcal virulence via global epigenetic changes
Author: Manso, A.
Chai, M.
Atack, J.
Furi, L.
Croix, M.
Haigh, R.
Trappetti, C.
Ogunniyi, A.
Shewell, L.
Boitano, M.
Clark, T.
Korlach, J.
Blades, M.
Mirkes, E.
Gorban, A.
Paton, J.
Jennings, M.
Oggioni, M.
Citation: Nature Communications, 2014; 5(1):5055-1-5055-9
Publisher: Nature
Issue Date: 2014
ISSN: 2041-1723
Statement of
Ana Sousa Manso, Melissa H. Chai, John M. Atack, Leonardo Furi, Megan De Ste Croix, Richard Haigh, Claudia Trappetti, Abiodun D. Ogunniyi, Lucy K. Shewell, Matthew Boitano, Tyson A. Clark, Jonas Korlach, Matthew Blades, Evgeny Mirkes, Alexander N. Gorban, James C. Paton, Michael P. Jennings, Marco R. Oggioni
Abstract: Streptococcus pneumoniae (the pneumococcus) is the world's foremost bacterial pathogen in both morbidity and mortality. Switching between phenotypic forms (or 'phases') that favour asymptomatic carriage or invasive disease was first reported in 1933. Here, we show that the underlying mechanism for such phase variation consists of genetic rearrangements in a Type I restriction-modification system (SpnD39III). The rearrangements generate six alternative specificities with distinct methylation patterns, as defined by single-molecule, real-time (SMRT) methylomics. The SpnD39III variants have distinct gene expression profiles. We demonstrate distinct virulence in experimental infection and in vivo selection for switching between SpnD39III variants. SpnD39III is ubiquitous in pneumococci, indicating an essential role in its biology. Future studies must recognize the potential for switching between these heretofore undetectable, differentiated pneumococcal subpopulations in vitro and in vivo. Similar systems exist in other bacterial genera, indicating the potential for broad exploitation of epigenetic gene regulation.
Keywords: Biological sciences; genetics; microbiology
Rights: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit
RMID: 0030012730
DOI: 10.1038/ncomms6055
Grant ID:
Appears in Collections:Molecular and Biomedical Science publications

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