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

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    Author(s)
    Atack, John M
    Srikhanta, Yogitha N
    Fox, Kate L
    Jurcisek, Joseph A
    Brockman, Kenneth L
    Clark, Tyson A
    Boitano, Matthew
    Power, Peter M
    Jen, Freda E-C
    McEwan, Alastair G
    Grimmond, Sean M
    Smith, Arnold L
    Barenkamp, Stephen J
    Korlach, Jonas
    Bakaletz, Lauren O
    Jennings, Michael P
    Griffith University Author(s)
    Jennings, Michael P.
    Jen, Freda E.
    Atack, John M.
    Year published
    2015
    Metadata
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    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) ...
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    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.
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    Journal Title
    Nature Communications
    Volume
    6
    DOI
    https://doi.org/10.1038/ncomms8828
    Copyright Statement
    © The Author(s) 2015. 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 http://creativecommons.org/licenses/by/4.0/
    Subject
    Bacteriology
    Publication URI
    http://hdl.handle.net/10072/168843
    Collection
    • Journal articles

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