The diversity of Klebsiella pneumoniae surface polysaccharides.
The diversity of Klebsiella pneumoniae surface polysaccharides.
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DOI：
10.1099/mgen.0.000073
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发表时间：
2016-08
影响因子：
3.9
通讯作者：
Thomson NR
中科院分区：
文献类型：
--
作者：
Follador R;Heinz E;Wyres KL;Ellington MJ;Kowarik M;Holt KE;Thomson NR
肺炎克雷伯氏菌被认为是一个紧迫的健康问题，因为出现了多药耐药菌株，疫苗接种提供了一个潜在的补救措施。基于表面多糖的疫苗是非常有前途的，但需要解决表面暴露的多糖的高度多样性，合成为O-抗原（脂多糖，LPS）和K-抗原（胶囊多糖，CPS），存在于K。肺炎。我们提出了一个全面的和临床相关的研究的多样性O-和K-抗原生物合成基因簇在全球收集超过500 K。肺炎全基因组序列和来自不同感染类型的人类分离株的血清流行病学。我们的研究定义了该集合中O-和K-抗原生物合成簇序列的遗传多样性，确定了已知血清型的序列，并确定了在循环当代分离株中发现的新型LPS和CPS基因簇。血清型O 1、O2和O3在我们的样本集中最普遍，约占所有感染的80%。与此相反，K血清型表现出一个数量级更高的多样性和感染类型之间的差异。此外，我们调查了O或K血清型与系统发生谱系、感染类型和已知毒力基因存在的潜在关联。K1和K2血清型与高毒力K.与其他常见的K血清型相比，肺炎克雷伯氏菌与更高丰度的毒力基因和更多样的O血清型相关。
Klebsiella pneumoniae is considered an urgent health concern due to the emergence of multi-drug-resistant strains for which vaccination offers a potential remedy. Vaccines based on surface polysaccharides are highly promising but need to address the high diversity of surface-exposed polysaccharides, synthesized as O-antigens (lipopolysaccharide, LPS) and K-antigens (capsule polysaccharide, CPS), present in K. pneumoniae. We present a comprehensive and clinically relevant study of the diversity of O- and K-antigen biosynthesis gene clusters across a global collection of over 500 K. pneumoniae whole-genome sequences and the seroepidemiology of human isolates from different infection types. Our study defines the genetic diversity of O- and K-antigen biosynthesis cluster sequences across this collection, identifying sequences for known serotypes as well as identifying novel LPS and CPS gene clusters found in circulating contemporary isolates. Serotypes O1, O2 and O3 were most prevalent in our sample set, accounting for approximately 80 % of all infections. In contrast, K serotypes showed an order of magnitude higher diversity and differ among infection types. In addition we investigated a potential association of O or K serotypes with phylogenetic lineage, infection type and the presence of known virulence genes. K1 and K2 serotypes, which are associated with hypervirulent K. pneumoniae, were associated with a higher abundance of virulence genes and more diverse O serotypes compared to other common K serotypes.