Seth-Smith Helena M B, Harris Simon R, Persson Kenneth, Marsh Pete, Barron Andrew, Bignell Alexandra, Bjartling Carina, Clark Louise, Cutcliffe Lesley T, Lambden Paul R, Lennard Nicola, Lockey Sarah J, Quail Michael A, Salim Omar, Skilton Rachel J, Wang Yibing, Holland Martin J, Parkhill Julian, Thomson Nicholas R, Clarke Ian N
Molecular Microbiology Group, University Medical School, Southampton General Hospital, Southampton, SO16 6YD, UK.
BMC Genomics. 2009 May 21;10:239. doi: 10.1186/1471-2164-10-239.
Chlamydia trachomatis is the most common cause of sexually transmitted infections globally and the leading cause of preventable blindness in the developing world. There are two biovariants of C. trachomatis: 'trachoma', causing ocular and genital tract infections, and the invasive 'lymphogranuloma venereum' strains. Recently, a new variant of the genital tract C. trachomatis emerged in Sweden. This variant escaped routine diagnostic tests because it carries a plasmid with a deletion. Failure to detect this strain has meant it has spread rapidly across the country provoking a worldwide alert. In addition to being a key diagnostic target, the plasmid has been linked to chlamydial virulence. Analysis of chlamydial plasmids and their cognate chromosomes was undertaken to provide insights into the evolutionary relationship between chromosome and plasmid. This is essential knowledge if the plasmid is to be continued to be relied on as a key diagnostic marker, and for an understanding of the evolution of Chlamydia trachomatis.
The genomes of two new C. trachomatis strains were sequenced, together with plasmids from six C. trachomatis isolates, including the new variant strain from Sweden. The plasmid from the new Swedish variant has a 377 bp deletion in the first predicted coding sequence, abolishing the site used for PCR detection, resulting in negative diagnosis. In addition, the variant plasmid has a 44 bp duplication downstream of the deletion. The region containing the second predicted coding sequence is the most highly conserved region of the plasmids investigated. Phylogenetic analysis of the plasmids and chromosomes are fully congruent. Moreover this analysis also shows that ocular and genital strains diverged from a common C. trachomatis progenitor.
The evolutionary pathways of the chlamydial genome and plasmid imply that inheritance of the plasmid is tightly linked with its cognate chromosome. These data suggest that the plasmid is not a highly mobile genetic element and does not transfer readily between isolates. Comparative analysis of the plasmid sequences has revealed the most conserved regions that should be used to design future plasmid based nucleic acid amplification tests, to avoid diagnostic failures.
沙眼衣原体是全球最常见的性传播感染病原体，也是发展中国家可预防失明的主要原因。沙眼衣原体有两种生物变种：引起眼部和生殖道感染的“沙眼”变种，以及具有侵袭性的“性病性淋巴肉芽肿”菌株。最近，瑞典出现了一种新的生殖道沙眼衣原体变种。该变种因携带一个有缺失的质粒而逃过了常规诊断检测。未能检测到这种菌株意味着它已在全国迅速传播，引发了全球警报。除了是关键的诊断靶点外，该质粒还与衣原体毒力有关。对衣原体质粒及其同源染色体进行分析，以深入了解染色体与质粒之间的进化关系。如果要继续将该质粒作为关键诊断标志物，并理解沙眼衣原体的进化，这是必不可少的知识。
对两株新的沙眼衣原体菌株的基因组进行了测序，并对来自六株沙眼衣原体分离株的质粒进行了测序，其中包括来自瑞典的新变种菌株。来自瑞典新变种的质粒在第一个预测编码序列中有377 bp的缺失，消除了用于PCR检测的位点，导致诊断为阴性。此外，变种质粒在缺失下游有44 bp的重复。包含第二个预测编码序列的区域是所研究质粒中最保守的区域。质粒和染色体的系统发育分析完全一致。此外，该分析还表明，眼部和生殖道菌株从一个共同的沙眼衣原体祖先进化而来。
衣原体基因组和质粒的进化途径表明，质粒的遗传与其同源染色体紧密相连。这些数据表明，质粒不是一个高度可移动的遗传元件，不易在分离株之间转移。质粒序列的比较分析揭示了最保守的区域，应利用这些区域设计未来基于质粒的核酸扩增检测，以避免诊断失败。
