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

• Published in: Nature communications Vol. 6; no. 1; p. 7828
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 28-07-2015; Nature Publishing Group; Nature Pub. Group
• Subjects: 38/1; 38/22; 38/23; 38/61; 38/77; 38/90; 631/208/176; 631/326/325/2482; 631/326/41/2534; 82/29; 82/58; Adaptation; Adaptation, Physiological - genetics; Alleles; Animals; Base Sequence; Biofilms; Chinchilla; Disease Models, Animal; DNA methylation; DNA Methylation - genetics; DNA, Bacterial - genetics; Ear diseases; Ear, Middle; Epigenesis, Genetic; Epigenetics; Gene expression; Haemophilus influenzae - genetics; Haemophilus influenzae - immunology; Haemophilus influenzae - pathogenicity; Humanities and Social Sciences; Immune Evasion - genetics; Infections; Medical research; Molecular Sequence Data; multidisciplinary; Otitis Media - microbiology; Pathogenesis; Pathogens; Research centers; Science; Science (multidisciplinary); Site-Specific DNA-Methyltransferase (Adenine-Specific) - genetics; Vaccines; Virulence; Virulence - genetics; Ohio; Queensland Australia; Australia; United States > US; St Lucia
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms8828

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.
Non-typeable
Haemophilus influenzae
, which causes ear and lung infections, has a DNA methyltransferase encoded by alternative alleles that are subject to random ON/OFF switching. Here, Atack
et al.
show that this epigenetic switch controls the expression of key proteins involved in virulence.