A random six-phase switch regulates pneumococcal virulence via global epigenetic changes

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 () and Marco R. Oggioni ()
Additional contact information
Ana Sousa Manso: University of Leicester
Melissa H. Chai: Research Centre for Infectious Diseases, School of Molecular and Biomedical Science, University of Adelaide
John M. Atack: Institute for Glycomics, Griffith University
Leonardo Furi: University of Leicester
Megan De Ste Croix: University of Leicester
Richard Haigh: University of Leicester
Claudia Trappetti: Research Centre for Infectious Diseases, School of Molecular and Biomedical Science, University of Adelaide
Abiodun D. Ogunniyi: Research Centre for Infectious Diseases, School of Molecular and Biomedical Science, University of Adelaide
Lucy K. Shewell: Institute for Glycomics, Griffith University
Matthew Boitano: Pacific Biosciences
Tyson A. Clark: Pacific Biosciences
Jonas Korlach: Pacific Biosciences
Matthew Blades: Bioinformatics and Biostatistics Analysis Support Hub, University of Leicester
Evgeny Mirkes: University of Leicester
Alexander N. Gorban: University of Leicester
James C. Paton: Research Centre for Infectious Diseases, School of Molecular and Biomedical Science, University of Adelaide
Michael P. Jennings: Institute for Glycomics, Griffith University
Marco R. Oggioni: University of Leicester

Nature Communications, 2014, vol. 5, issue 1, 1-9

Abstract: 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.

Date: 2014
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DOI: 10.1038/ncomms6055

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