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A biphasic epigenetic switch controls immunoevasion, virulence and niche adaptation in non-typeable Haemophilus influenzae

Author

Listed:
  • John M. Atack

    (Institute for Glycomics, Griffith University)

  • Yogitha N. Srikhanta

    (Institute for Glycomics, Griffith University
    Present address: School of Biomedical Science, Monash University, Melbourne, Victoria 3800, Australia)

  • Kate L. Fox

    (School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia)

  • Joseph A. Jurcisek

    (Center for Microbial Pathogenesis, The Research Institute at Nationwide Children’s Hospital and The Ohio State University College of Medicine)

  • Kenneth L. Brockman

    (Center for Microbial Pathogenesis, The Research Institute at Nationwide Children’s Hospital and The Ohio State University College of Medicine)

  • Tyson A. Clark

    (Pacific Biosciences)

  • Matthew Boitano

    (Pacific Biosciences)

  • Peter M. Power

    (Institute for Glycomics, Griffith University)

  • Freda E.-C. Jen

    (Institute for Glycomics, Griffith University)

  • Alastair G. McEwan

    (School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia)

  • Sean M. Grimmond

    (Institute of Molecular Bioscience, The University of Queensland, St Lucia
    Present address: Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow, Scotland G61 1BD, UK)

  • Arnold L. Smith

    (Center for Global Infectious Disease Research, Seattle Children's Research Institute)

  • Stephen J. Barenkamp

    (Saint Louis University School of Medicine, and the Pediatric Research Institute, Cardinal Glennon Children’s Medical Center)

  • Jonas Korlach

    (Pacific Biosciences)

  • Lauren O. Bakaletz

    (Center for Microbial Pathogenesis, The Research Institute at Nationwide Children’s Hospital and The Ohio State University College of Medicine)

  • Michael P. Jennings

    (Institute for Glycomics, Griffith University)

Abstract

Non-typeable Haemophilus influenzae contains an N6-adenine DNA-methyltransferase (ModA) that is subject to phase-variable expression (random ON/OFF switching). Five modA alleles, modA2, modA4, modA5, modA9 and modA10, account for over two-thirds of clinical otitis media isolates surveyed. Here, we use single molecule, real-time (SMRT) methylome analysis to identify the DNA-recognition motifs for all five of these modA alleles. Phase variation of these alleles regulates multiple proteins including vaccine candidates, and key virulence phenotypes such as antibiotic resistance (modA2, modA5, modA10), biofilm formation (modA2) and immunoevasion (modA4). Analyses of a modA2 strain in the chinchilla model of otitis media show a clear selection for ON switching of modA2 in the middle ear. Our results indicate that a biphasic epigenetic switch can control bacterial virulence, immunoevasion and niche adaptation in an animal model system.

Suggested Citation

  • John M. Atack & Yogitha N. Srikhanta & Kate L. Fox & Joseph A. Jurcisek & Kenneth L. Brockman & Tyson A. Clark & Matthew Boitano & Peter M. Power & Freda E.-C. Jen & Alastair G. McEwan & Sean M. Grimm, 2015. "A biphasic epigenetic switch controls immunoevasion, virulence and niche adaptation in non-typeable Haemophilus influenzae," Nature Communications, Nature, vol. 6(1), pages 1-12, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8828
    DOI: 10.1038/ncomms8828
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