Actinobacillus pleuropneumoniae encodes multiple phase-variable DNA methyltransferases that control distinct phasevarions.
Actinobacillus pleuropneumoniae encodes multiple phase-variable DNA methyltransferases that control distinct phasevarions.
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DOI：
10.1093/nar/gkad091
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发表时间：
2023-04-24
影响因子：
14.9
通讯作者：
中科院分区：
文献类型：
--
作者：
胸膜肺炎放线杆菌是猪胸膜肺炎的病原，胸膜肺炎是一种严重的呼吸道感染，给养猪业造成重大经济损失。许多适应宿主的细菌病原体编码称为相位可变调节子（phase-variable regulons）的系统。相变异体由细胞质DNA甲基转移酶的可变表达引起。可变表达导致细菌群体内的全基因组甲基化差异，从而通过表观遗传机制导致多个基因的表达改变。我们对A.胸膜肺炎菌株确定具有阶段变化标志的I型和III型DNA甲基转移酶存在于该物种中。我们表明，相位变化发生在这些甲基转移酶，并显示特定的III型甲基转移酶等位基因和血清型之间的关联。使用Pacific BioSciences单分子实时（SMRT）测序和Oxford Nanopore测序，我们证明了第一个表征的相位可变，胞嘧啶特异性III型DNA甲基转移酶的存在。不同的III型DNA甲基转移酶在A.胸膜肺炎导致调节不同的阶段变化，并导致与病理生物学相关的多种表型差异。我们对A.胸膜肺炎的研究将有助于选择稳定表达的抗原，并指导和告知针对这种主要兽医病原体的合理设计的亚单位疫苗的开发。
Actinobacillus pleuropneumoniae is the cause of porcine pleuropneumonia, a severe respiratory tract infection that is responsible for major economic losses to the swine industry. Many host-adapted bacterial pathogens encode systems known as phasevarions (phase-variable regulons). Phasevarions result from variable expression of cytoplasmic DNA methyltransferases. Variable expression results in genome-wide methylation differences within a bacterial population, leading to altered expression of multiple genes via epigenetic mechanisms. Our examination of a diverse population of A. pleuropneumoniae strains determined that Type I and Type III DNA methyltransferases with the hallmarks of phase variation were present in this species. We demonstrate that phase variation is occurring in these methyltransferases, and show associations between particular Type III methyltransferase alleles and serovar. Using Pacific BioSciences Single-Molecule, Real-Time (SMRT) sequencing and Oxford Nanopore sequencing, we demonstrate the presence of the first ever characterised phase-variable, cytosine-specific Type III DNA methyltransferase. Phase variation of distinct Type III DNA methyltransferase in A. pleuropneumoniae results in the regulation of distinct phasevarions, and in multiple phenotypic differences relevant to pathobiology. Our characterisation of these newly described phasevarions in A. pleuropneumoniae will aid in the selection of stably expressed antigens, and direct and inform development of a rationally designed subunit vaccine against this major veterinary pathogen.
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DOI：
10.1016/j.meegid.2008.11.006
发表时间：
2009-03
期刊：
Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases
影响因子：
--
作者：
Power PM;Sweetman WA;Gallacher NJ;Woodhall MR;Kumar GA;Moxon ER;Hood DW
通讯作者：
Hood DW
影响因子：
6.4
作者：
Chiers, K;van Overbeke, I;Haesebrouck, F
通讯作者：
Haesebrouck, F
影响因子：
3.2
作者：
通讯作者：
--
影响因子：
3.3
作者：
Blakeway, Luke V.;Tan, Aimee;Seib, Kate L.
通讯作者：
Seib, Kate L.
影响因子：
6.4
作者：
Brockman KL;Azzari PN;Branstool MT;Atack JM;Schulz BL;Jen FE;Jennings MP;Bakaletz LO
通讯作者：
Bakaletz LO