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Nat Commun. 2014 Sep 30;5:5055. doi: 10.1038/ncomms6055.

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

Author information

1
1] Department of Genetics, University of Leicester, Leicester LE1 7RH, UK [2] Dipartimento di Biotechnologie Mediche, Università di Siena, 53100 Siena, Italy.
2
Research Centre for Infectious Diseases, School of Molecular and Biomedical Science, University of Adelaide, Adelaide, South Australia 5005, Australia.
3
Institute for Glycomics, Griffith University, Southport, Queensland 4215, Australia.
4
Department of Genetics, University of Leicester, Leicester LE1 7RH, UK.
5
Pacific Biosciences, Menlo Park, California 94025, USA.
6
Bioinformatics and Biostatistics Analysis Support Hub, University of Leicester, Leicester LE1 7RH, UK.
7
Department of Mathematics, University of Leicester, Leicester LE1 7RH, UK.
8
1] Institute for Glycomics, Griffith University, Southport, Queensland 4215, Australia [2].
9
1] Department of Genetics, University of Leicester, Leicester LE1 7RH, UK [2] Dipartimento di Biotechnologie Mediche, Università di Siena, 53100 Siena, Italy [3].

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.

Comment in

PMID:
25268848
PMCID:
PMC4190663
DOI:
10.1038/ncomms6055
[Indexed for MEDLINE]
Free PMC Article

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