Chlamydia trachomatis: when the virulence-associated genome backbone imports a prevalence-associated major antigen signature

Chlamydia trachomatis: when the virulence-associated genome backbone imports a prevalence-associated major antigen signature
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DOI:
10.1099/mgen.0.000313
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发表时间:
2019-11-01
期刊:
影响因子:
3.9
通讯作者:
Gomes, Joao Paulo
Gomes, Joao Paulo
中科院分区:
生物学2区
文献类型:
--
作者:
Borges, Vitor;Cordeiro, Dora;Gomes, Joao Paulo

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沙眼衣原体是世界范围内最普遍的性传播细菌,也是沙眼的病原体。其菌株根据ompA基因型进行分类,ompA基因型与不同的组织嗜性和疾病结局[眼部疾病、泌尿生殖系统疾病和性病淋巴肉芽肿(LGV)]密切相关。虽然基于基因组的物种系统发育树呈现了与向性/流行性相关的四个主要分支,即眼、LGV、泌尿生殖器T1(更流行的基因型)和泌尿生殖器T2(不太流行的基因型),但ompA的分支间交换被认为是一种罕见的现象,可能介导显著的向性改变。在过去的几十年里,与L2 b基因型的克隆扩张相关的LGV流行病已经出现,特别是由于其非典型的临床表现(溃疡性直肠炎)和男男性行为者(MSM)之间的循环引起了人们的关注。在这里,我们报告了LGV爆发,主要影响人类免疫缺陷病毒阳性的男男性接触者从事高风险的性行为,由L2 b株引起的,具有相当独特的非LGV ompA签名,排除了实验室通知本次爆发LGV。C.直接从临床样品中捕获沙眼衣原体全基因组并测序,以深入表征这种新的LGV爆发引起克隆的基因组骨架。它揭示了一种嵌合基因组结构,这是由于ompA和四个相邻基因从血清型D/Da菌株遗传转移到LGV(L2 b)菌株,该菌株可能具有与更普遍的泌尿生殖基因型(T1进化枝)相关的基因组骨架。杂合L2 b/D-Da毒株呈现粘附素和免疫显性抗原MOMP(主要外膜蛋白)(由ompA编码),其具有非侵入性生殖器毒株典型的表位库,同时保持经典LGV毒株的基因组分散的毒力指纹。如先前报道的非LGV分支间ompA交换,这种新的C。沙眼衣原体基因组嵌合体涉及当代流行病学和临床相关的LGV株可能对其传播,组织嗜性和致病能力有影响。具有流行和致病潜力的变异的出现突出了需要更有针对性的监测策略来捕获C。沙眼的进化
Chlamydia trachomatis is the most prevalent sexually transmitted bacterium worldwide and the causative agent of trachoma. Its strains are classified according to their ompA genotypes, which are strongly linked to differential tissue tropism and disease outcomes [ocular disease, urogenital disease and lymphogranuloma venereum (LGV)]. While the genome-based species phylogenetic tree presents four main clades correlating with tropism/prevalence, namely ocular, LGV, urogenital T1 (more prevalent genotypes) and urogenital T2 (less prevalent genotypes), inter-clade exchange of ompA is considered a rare phenomenon probably mediating marked tropism alterations. An LGV epidemic, associated with the clonal expansion of the L2b genotype, has emerged in the last few decades, raising concerns particularly due to its atypical clinical presentation (ulcerative proctitis) and circulation among men who have sex with men (MSM). Here, we report an LGV outbreak, mostly affecting human immunodeficiency virus-positive MSM engaging in high-risk sexual practices, caused by an L2b strain with a rather unique non-LGV ompA signature that precluded the laboratory notification of this outbreak as LGV. C. trachomatis whole-genome capture and sequencing directly from clinical samples was applied to deeply characterize the genomic backbone of this novel LGV outbreak-causing clone. It revealed a chimeric genome structure due to the genetic transfer of ompA and four neighbouring genes from a serovar D/Da strain, likely possessing the genomic backbone associated with the more prevalent urogenital genotypes (T1 clade), to an LGV (L2b) strain. The hybrid L2b/D-Da strain presents the adhesin and immunodominant antigen MOMP (major outer membrane protein) (encoded by ompA) with an epitope repertoire typical of non-invasive genital strains, while keeping the genome-dispersed virulence fingerprint of a classical LGV strain. As previously reported for inter-clade ompA exchange among non-LGV clades, this novel C. trachomatis genomic mosaic involving a contemporary epidemiologically and clinically relevant LGV strain may have implications on its transmission, tissue tropism and pathogenic capabilities. The emergence of variants with epidemic and pathogenic potential highlights the need for more focused surveillance strategies to capture C. trachomatis evolution in action.