Genomic Analysis of an Attenuated Chlamydia abortus Live Vaccine Strain Reveals Defects in Central Metabolism and Surface Proteins
Genomic Analysis of an Attenuated Chlamydia abortus Live Vaccine Strain Reveals Defects in Central Metabolism and Surface Proteins
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DOI：
10.1128/iai.00189-09
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发表时间：
2009-09-01
影响因子：
3.1
通讯作者：
Bavoil, P. M.
中科院分区：
文献类型：
--
作者：
Burall, L. S.;Rodolakis, A.;Bavoil, P. M.
对绵羊病原体流产衣原体野生型菌株及其亚硝基胍诱导的、温度敏感的、毒力减弱的活疫苗衍生物进行比较基因组分析，发现了该突变体特有的22个单核苷酸多态性，包括9个非同义突变，其中一个导致编码多态性膜蛋白的pmpG截短，以及两个可能影响启动子序列的基因间突变。其他非同义突变映射到一个pmpG假基因和预测的编码序列编码一个假定的脂蛋白，一个σ-54依赖性反应调节，PHOH样蛋白，一个假定的输出蛋白，两个tRNA合成酶，和一个假定的丝氨酸羟甲基转移酶。其中一个基因间突变puppet影响两个不同的基因的转录，分别编码丙酮酸激酶和一个推定的SOS反应核酸酶。这些观察结果表明，由于丙酮酸激酶表达改变和/或一种或多种膜蛋白（最明显的是PmpG和推定脂蛋白）功能改变导致代谢活性破坏，导致疫苗株的温度敏感型和相关毒力衰减。
Comparative genomic analysis of a wild-type strain of the ovine pathogen Chlamydia abortus and its nitrosoguanidine-induced, temperature-sensitive, virulence-attenuated live vaccine derivative identified 22 single nucleotide polymorphisms unique to the mutant, including nine nonsynonymous mutations, one leading to a truncation of pmpG, which encodes a polymorphic membrane protein, and two intergenic mutations potentially affecting promoter sequences. Other nonsynonymous mutations mapped to a pmpG pseudogene and to predicted coding sequences encoding a putative lipoprotein, a sigma-54-dependent response regulator, a PhoH-like protein, a putative export protein, two tRNA synthetases, and a putative serine hydroxymethyltransferase. One of the intergenic mutations putatively affects transcription of two divergent genes encoding pyruvate kinase and a putative SOS response nuclease, respectively. These observations suggest that the temperature-sensitive phenotype and associated virulence attenuation of the vaccine strain result from disrupted metabolic activity due to altered pyruvate kinase expression and/or alteration in the function of one or more membrane proteins, most notably PmpG and a putative lipoprotein.