title: A biphasic epigenetic switch controls immunoevasion, virulence and niche adaptation in non-typeable Haemophilus influenzae.
abstract: Non-typeable Haemophilus influenzae contains an N(6)-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.
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast, Queensland 4222, Australia.
authors.forename: John M
authors.initials: JM
authors.lastname: Atack
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast, Queensland 4222, Australia.
authors.forename: Yogitha N
authors.initials: YN
authors.lastname: Srikhanta
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia.
authors.forename: Kate L
authors.initials: KL
authors.lastname: Fox
authors.affiliation: Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital and The Ohio State University College of Medicine, Columbus, Ohio 43205, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Jurcisek
authors.affiliation: Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital and The Ohio State University College of Medicine, Columbus, Ohio 43205, USA.
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Brockman
authors.affiliation: Pacific Biosciences, 1380 Willow Road, Menlo Park, California 94025, USA.
authors.forename: Tyson A
authors.initials: TA
authors.lastname: Clark
authors.affiliation: Pacific Biosciences, 1380 Willow Road, Menlo Park, California 94025, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Boitano
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast, Queensland 4222, Australia.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Power
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast, Queensland 4222, Australia.
authors.forename: Freda E-C
authors.initials: FE
authors.lastname: Jen
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia.
authors.forename: Alastair G
authors.initials: AG
authors.lastname: McEwan
authors.affiliation: Institute of Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia.
authors.forename: Sean M
authors.initials: SM
authors.lastname: Grimmond
authors.affiliation: Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, Washington 98105, USA.
authors.forename: Arnold L
authors.initials: AL
authors.lastname: Smith
authors.affiliation: Department of Pediatrics, Saint Louis University School of Medicine, and the Pediatric Research Institute, Cardinal Glennon Children's Medical Center, Saint Louis, Missouri 63104, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Barenkamp
authors.affiliation: Pacific Biosciences, 1380 Willow Road, Menlo Park, California 94025, USA.
authors.forename: Jonas
authors.initials: J
authors.lastname: Korlach
authors.affiliation: Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital and The Ohio State University College of Medicine, Columbus, Ohio 43205, USA.
authors.forename: Lauren O
authors.initials: LO
authors.lastname: Bakaletz
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast, Queensland 4222, Australia.
authors.forename: Michael P
authors.identifier: 0000000210274684
authors.initials: MP
authors.lastname: Jennings
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics*; D000483:Alleles; D000818:Animals; D001483:Base Sequence; D018441:Biofilms; D002682:Chinchilla; D019175:DNA Methylation / Q000235:genetics*; D004269:DNA, Bacterial / Q000235:genetics*; D004195:Disease Models, Animal; D004432:Ear, Middle; D044127:Epigenesis, Genetic; D006193:Haemophilus influenzae / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity; D057131:Immune Evasion / Q000235:genetics*; D008969:Molecular Sequence Data; D010033:Otitis Media / Q000382:microbiology; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific) / Q000235:genetics*; D014774:Virulence / Q000235:genetics
chemical_list: D004269:DNA, Bacterial; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific)