Genotypic differences in the Chlamydia pneumoniae tyrP locus related to vascular tropism and pathogenicity

Genotypic differences in the Chlamydia pneumoniae tyrP locus related to vascular tropism and pathogenicity
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DOI:
10.1086/378692
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发表时间:
2003-10-15
影响因子:
6.4
通讯作者:
Belland, RJ
Belland, RJ
中科院分区:
医学2区
文献类型:
--
作者:
Gieffers, J;Durling, L;Belland, RJ

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肺炎衣原体是一种专性细胞内病原体,可引起呼吸道感染并与心血管疾病相关。我们比较了呼吸道和心血管分离株,以发现与致病性相关的遗传差异。发现编码酪氨酸/色氨酸通透酶的多态性区域在疾病分离株之间存在差异。呼吸道菌株含有 tyrP 基因的多个拷贝,而血管菌株含有一个拷贝。单核苷酸多态性分析揭示了重复是系统发育上古老的事件。基因扩增与较高的 mRNA 水平和底物酪氨酸的较高摄取相关,表明与 tyrP 基因型相关的氨基酸转运相关表型。血管菌株尽管运输酪氨酸的能力降低,但在体外的生长速度似乎并未降低。我们假设,血管源菌株和呼吸源菌株之间的重要区别可能在于,血管菌株更容易引发由氨基酸饥饿引发的持续感染。
Chlamydia pneumoniae is an obligate intracellular pathogen that causes respiratory infections and has been associated with cardiovascular disease. We compared respiratory and cardiovascular isolates to find genetic differences associated with pathogenicity. A polymorphic region encoding a tyrosine/tryptophan permease was found to differ between disease isolates. Respiratory strains contained multiple copies of the tyrP gene, and vascular strains contained a single copy. Single-nucleotide polymorphism analysis revealed the duplication to be a phylogenetically old event. Gene amplification was associated with higher mRNA levels and higher uptake of the substrate tyrosine, indicating an amino-acid transport-related phenotype associated with the tyrP genotype. Vascular strains, despite their reduced ability to transport tyrosine, do not appear to have a reduced growth rate in vitro. We hypothesize that the important difference between strains of vascular and respiratory origin may lie in the increased tendency of vascular strains to elicit persistent infection that is triggered by amino-acid starvation.