Smelov Vitaly, Vrbanac Alison, van Ess Eleanne F, Noz Marlies P, Wan Raymond, Eklund Carina, Morgan Tyler, Shrier Lydia A, Sanders Blake, Dillner Joakim, de Vries Henry J C, Morre Servaas A, Dean Deborah
International Agency for Research on Cancer, World Health Organization, Lyon, France.
Karolinska Institute, Stockholm, Sweden.
Front Microbiol. 2017 Nov 13;8:2195. doi: 10.3389/fmicb.2017.02195. eCollection 2017.
() is the leading cause of bacterial sexually transmitted diseases worldwide. The Multi Locus Sequence Typing (MLST) scheme is effective in differentiating strain types (ST), deciphering transmission patterns and treatment failure, and identifying recombinant strains. Here, we analyzed 323 reference and clinical samples, including 58 samples from Russia, an area that has not previously been represented in typing schemes, to expand our knowledge of the global diversification of STs. The 323 samples resolved into 84 unique STs, a 3.23 higher typing resolution compared to the gold standard single locus A genotyping. Our MLST scheme showed a high discriminatory index, , of 0.98 (95% CI 0.97-0.99) confirming the validity of this method for typing. Phylogenetic analyses revealed distinct branches for the phenotypic diseases of lymphogranuloma venereum, urethritis and cervicitis, and a sub-branch for ocular trachoma. Consistent with these findings, single nucleotide polymorphisms were identified that significantly correlated with each phenotype. While the overall number of unique STs per region was comparable across geographies, the number of STs was greater for Russia with a significantly higher ST/sample ratio of 0.45 (95% CI: 0.35-0.53) compared to Europe or the Americas ( < 0.009), which may reflect a higher level of sexual mixing with the introduction of STs from other regions and/or reassortment of alleles. Four STs were found to be significantly associated with a particular geographic region. ST23 [ = 0.032 (95% CI: 1-23)], ST34 [ = 0.019 (95% CI: 1.1-25)]; and ST19 [ = 0.001 (95% CI: 1.7-34.7)] were significantly associated with Netherlands compared to Russia or the Americas, while ST 30 [ = 0.031 (95% CI: 1.1-17.8)] was significantly associated with the Americas. ST19 was significantly associated with Netherlands and Russia compared with the Americans [ = 0.001 (95% CI: 1.7-34.7) and = 0.006 (95% CI: 1.5-34.6), respectively]. Additionally, recombinant strains were ubiquitous in the data set [106 (32.8%)], although Europe had a significantly higher number than Russia or the Americas ( < 0.04), the majority of which were from Amsterdam [43 (87.8%) of 49)]. The higher number of recombinants in Europe indicates selective pressure and/or adaptive diversification that will require additional studies to elucidate.
()是全球细菌性性传播疾病的主要病因。多位点序列分型(MLST)方案在区分菌株类型(ST)、解读传播模式和治疗失败情况以及识别重组菌株方面很有效。在此,我们分析了323份参考样本和临床样本,其中包括来自俄罗斯的58份样本,俄罗斯地区此前未在分型方案中有所体现,以此来扩展我们对全球STs多样化的认识。这323份样本解析为84个独特的STs,与金标准单一位点A基因分型相比,分型分辨率高3.23倍。我们的MLST方案显示出较高的鉴别指数,即0.98(95%置信区间0.97 - 0.99),证实了该分型方法的有效性。系统发育分析揭示了性病性淋巴肉芽肿、尿道炎和宫颈炎的表型疾病有不同分支,以及沙眼有一个亚分支。与这些发现一致,鉴定出了与每种表型显著相关的单核苷酸多态性。虽然每个地区独特STs的总数在不同地理区域之间具有可比性,但俄罗斯的STs数量更多,与欧洲或美洲相比,其ST/样本比率显著更高,为0.45(95%置信区间:0.35 - 0.53)(P < 0.009),这可能反映了随着其他地区STs的引入和/或等位基因的重配,性混合程度更高。发现有4个STs与特定地理区域显著相关。与俄罗斯或美洲相比,ST23 [P = 0.032(95%置信区间:1 - 23)]、ST34 [P = 0.019(95%置信区间:1.1 - 25)];以及ST19 [P = 0.001(95%置信区间:1.7 - 34.7)]与荷兰显著相关,而ST 30 [P = 0.031(95%置信区间:1.1 - 17.8)]与美洲显著相关。与美国人相比,ST19与荷兰和俄罗斯显著相关[分别为P = 0.001(95%置信区间:1.7 - 34.7)和P = 0.006(95%置信区间:1.5 - 34.6)]。此外,重组菌株在数据集中普遍存在[106个(32.8%)],尽管欧洲的数量显著高于俄罗斯或美洲(P < 0.04),其中大多数来自阿姆斯特丹[49个中的43个(87.8%)]。欧洲重组菌株数量较多表明存在选择压力和/或适应性多样化,这需要进一步研究来阐明。