Polymorphisms in Chlamydia trachomatis tryptophan synthase genes differentiate between genital and ocular isolates
Polymorphisms in Chlamydia trachomatis tryptophan synthase genes differentiate between genital and ocular isolates
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DOI：
10.1172/jci17993
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发表时间：
2003-06-01
影响因子：
15.9
通讯作者：
McClarty, G
中科院分区：
文献类型：
--
作者：
Caldwell, HD;Wood, H;McClarty, G
我们之前曾报道过，感染器官趋向性不同的实验室参考沙眼衣原体菌株与病原体的色氨酸合成酶(TrpBA)基因的失活突变有关。在这里，我们应用功能基因组学来扩展这项工作，并发现为参考血清型建立的范式也适用于临床分离株--具体地说，所有测试的眼部沙眼分离株都具有合酶失活突变，而所有生殖器分离株编码一种功能酶。此外，功能性酶活性通过吲哚拯救机制与干扰素-γ抗性直接相关。因此，生殖器菌株存在很大的选择压力，以维持能够利用吲哚进行色氨酸生物合成的功能合酶。从生殖道分离的眼部血清型(B血清型)被发现具有功能性合成酶，这一事实为这种联系提供了更有说服力的证据。这些结果表明，衣原体生殖器株和人类宿主之间存在着重要的宿主-寄生虫关系，这种关系决定了感染的器官嗜性和疾病的病理生理学。我们推测，这种关系涉及阴道微生物菌群的组成部分产生吲哚，使衣原体逃脱干扰素-伽马介导的根除，从而建立持续感染。
We previously reported that laboratory reference strains of Chlamydia trachomatis differing in infection organotropism correlated with inactivating mutations in the pathogen's tryptophan synthase (trpBA) genes. Here, we have applied functional genomics to extend this work and find that the paradigm established for reference serovars also applies to clinical isolates - specifically, all ocular trachoma isolates tested have inactivating mutations in the synthase, whereas all genital isolates encode a functional enzyme. Moreover, functional enzyme activity was directly correlated to IFN-gamma resistance through an indole rescue mechanism. Hence, a strong selective pressure exists for genital strains to maintain a functional synthase capable of using indole for tryptophan biosynthesis. The fact that ocular serovars (serovar B) isolated from the genital tract were found to possess a functional synthase provided further persuasive evidence of this association. These results argue that there is an important host-parasite relationship between chlamydial genital strains and the human host that determines organotropism of infection and the pathophysiology of disease. We speculate that this relationship involves the production of indole by components of the vaginal microbial flora, allowing chlamydiae to escape IFN-gamma-mediated eradication and thus establish persistent infection.