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.

中文翻译：

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双相表观遗传开关控制不可分型流感嗜血杆菌的免疫逃避，毒力和生态位适应。

不可分型的流感嗜血杆菌含有N（6）-腺嘌呤DNA-甲基转移酶（ModA），该表达会发生相变表达（随机ON / OFF切换）。五个modA等位基因modA2，modA4，modA5，modA9和modA10占所调查临床中耳炎分离株的三分之二以上。在这里，我们使用单分子实时（SMRT）甲基化分析来识别所有这五个modA等位基因的DNA识别基序。这些等位基因的相变可调节多种蛋白质，包括候选疫苗和关键毒力表型，例如抗生素抗性（modA2，modA5，modA10），生物膜形成（modA2）和免疫逃逸（modA4）。在中耳炎的黄鼠模型中对modA2菌株的分析表明，中耳中modA2的ON切换是一个明确的选择。