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Comparative Genomic Analysis of Chlamydia trachomatis Oculotropic and Genitotropic Strains

机译:沙眼衣原体亲卵和生殖生殖菌株的比较基因组分析

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Chlamydia trachomatis infection is an important cause of preventable blindness and sexually transmitted disease (STD) in humans. C. trachomatis exists as multiple serovariants that exhibit distinct organotropism for the eye or urogenital tract. We previously reported tissue-tropic correlations with the presence or absence of a functional tryptophan synthase and a putative GTPase-inactivating domain of the chlamydial toxin gene. This suggested that these genes may be the primary factors responsible for chlamydial disease organotropism. To test this hypothesis, the genome of an oculotropic trachoma isolate (A/HAR-13) was sequenced and compared to the genome of a genitotropic (D/UW-3) isolate. Remarkably, the genomes share 99.6% identity, supporting the conclusion that a functional tryptophan synthase enzyme and toxin might be the principal virulence factors underlying disease organotropism. Tarp (translocated actin-recruiting phosphoprotein) was identified to have variable numbers of repeat units within the N and C portions of the protein. A correlation exists between lymphogranuloma venereum serovars and the number of N-terminal repeats. Single-nucleotide polymorphism (SNP) analysis between the two genomes highlighted the minimal genetic variation. A disproportionate number of SNPs were observed within some members of the polymorphic membrane protein (pmp) autotransporter gene family that corresponded to predicted T-cell epitopes that bind HLA class I and II alleles. These results implicate Pmps as novel immune targets, which could advance future chlamydial vaccine strategies. Lastly, a novel target for PCR diagnostics was discovered that can discriminate between ocular and genital strains. This discovery will enhance epidemiological investigations in nations where both trachoma and chlamydial STD are endemic.
机译:沙眼衣原体感染是人类可预防的失明和性传播疾病(STD)的重要原因。 C。沙眼以多种血清变异体的形式存在,对眼睛或泌尿生殖道表现出明显的嗜有机性。我们以前曾报道与衣原体毒素基因功能性色氨酸合酶和推定的GTPase失活域的存在或不存在的组织相关性。这表明这些基因可能是衣原体疾病嗜有机性的主要因素。为了检验该假设,对亲眼性沙眼分离株(A / HAR-13)的基因组进行了测序,并与遗传分离(D / UW-3)分离株的基因组进行了比较。值得注意的是,这些基因组具有99.6%的同一性,支持以下结论:功能性色氨酸合酶和毒素可能是导致疾病嗜有机性的主要毒力因子。已确定Tarp(易位肌动蛋白磷酸化蛋白)在蛋白的N和C部分具有可变数量的重复单元。性病性淋巴肉芽肿与N末端重复数之间存在相关性。两个基因组之间的单核苷酸多态性(SNP)分析强调了最小的遗传变异。在多态性膜蛋白( pmp )自转运基因家族的某些成员中观察到不成比例的SNP,这些成员对应于预测的结合HLA I类和II类等位基因的T细胞表位。这些结果暗示Pmps作为新的免疫靶标,可以促进未来的衣原体疫苗策略。最后,发现了一种新的PCR诊断靶标,可以区分眼部和生殖器菌株。这一发现将加强在沙眼和衣原体性病都流行的国家中的流行病学调查。

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