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

作者：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

来源：Nature Communications, 2015, 6(1): 7828.

DOI：10.1038/ncomms8828

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.

• 出版日期2015-7