Phenotypic diversity and shared genomic determinants among isolates causing a large incidence of disseminated gonococcal infections in Canada

Gursonika Binepal, Emil Jurga, Duncan Carruthers-Lay, Sören Krüger, Sandra Zittermann, Jessica Minion, Mathew Diggle, David C. Alexander, Irene Martin, Vanessa Allen, John Parkinson, Scott D. Gray-Owen
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Abstract

The incidence of disseminated gonococcal infection (DGI) has remained low since the advent of antibiotics, however recent surge in DGI have inexplicably emerged within several regions during the past decade. In an effort to understand whether Neisseria gonorrhoeae that cause disseminated disease can be differentiated from non-invasive strains, we have performed a phenotypic and genotypic analysis on a selection of isolates obtained from invasive and uncomplicated infections in Canada. Phenotypic analysis of a matched subset of 19 isolates obtained since 2013 found that these varied in their capacity to aggregate in suspension and in their association with serum complement proteins, however these interactions did not discriminate between the invasive and mucosal isolates. Sequence typing of 360 Canadian isolates revealed that two porB alleles are significantly associated with the DGI strains, one of these being present throughout the past decade whereas the other became associated more recently. A PopNet-based population dynamics analysis, which instead establishes relationships based upon variance among discrete chromosomal segments, found that DGI isolates were restricted in their phylogenetic distribution. While this implies a genetically-linked potential to cause invasive disease, it cannot distinguish between an inherent difference in the phenotype of these populations or the horizontal exchange of some virulence factor among closely related strains. Regardless, a large number of genetic determinants are enriched in the DGI strains, making these enticing candidates for future work to understand how they might either promote the gonococcal capacity to cause systemic infection or reduce the presentation of clinical symptoms from localized infection so that it remains untreated.
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加拿大引起大量传播性淋球菌感染的分离株之间的表型多样性和共同基因组决定因素
自抗生素问世以来,播散性淋球菌感染(DGI)的发病率一直很低,但在过去十年中,一些地区却莫名其妙地出现了播散性淋球菌感染的激增。为了了解是否能将引起传播性疾病的淋病奈瑟菌与非侵袭性菌株区分开来,我们对从加拿大侵袭性和非侵袭性感染中分离出来的部分菌株进行了表型和基因型分析。对自2013年以来获得的19株分离株的匹配子集进行表型分析后发现,这些分离株在悬浮液中聚集的能力以及与血清补体蛋白的关联各不相同,但这些相互作用并不能区分侵袭性分离株和粘膜分离株。对 360 个加拿大分离株进行序列分型后发现,有两个 porB 等位基因与 DGI 菌株有显著关联,其中一个在过去十年中一直存在,而另一个则是最近才出现的。基于 PopNet 的种群动态分析发现,DGI 株系的系统发育分布受到限制,而 PopNet 是根据离散染色体片段之间的差异建立关系的。虽然这意味着这些种群有可能在遗传上引起入侵性疾病,但它并不能区分这些种群的表型存在固有差异,还是近缘菌株之间的某些毒力因子发生了水平交换。无论如何,DGI 菌株中富含大量的遗传决定因素,这使它们成为未来工作的诱人候选者,以了解它们如何促进淋球菌引起全身性感染的能力,或减少局部感染引起的临床症状,从而使其不被治疗。
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