D-galactan II is an immunodominant antigen in O1 lipopolysaccharide and affects virulence in Klebsiella pneumoniae: implication in vaccine design.

D-galactan II is an immunodominant antigen in O1 lipopolysaccharide and affects virulence in Klebsiella pneumoniae: implication in vaccine design.
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D-Galactan II是O1脂多糖中的一种免疫主导抗原,会影响肺炎克雷伯氏菌的毒力:对疫苗设计的影响。

DOI:
10.3389/fmicb.2014.00608
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发表时间:
2014
影响因子:
5.2
通讯作者:
Wang JT
Wang JT
中科院分区:
生物学2区
文献类型:
--
作者:
Hsieh PF;Wu MC;Yang FL;Chen CT;Lou TC;Chen YY;Wu SH;Sheu JC;Wang JT

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在克雷伯氏菌O1菌株中,脂多糖(LPS)O-抗原由D-半乳聚糖I和D-半乳聚糖II组成。尽管克雷伯菌 O1 抗原的组成已被解决了二十多年,但参与 D-半乳聚糖 II 生物合成的遗传位点以及 D-半乳聚糖 II 在细菌发病机制中的作用仍不清楚。在这里,我们报告了通过用噬菌体筛选封装的肺炎克雷伯菌 O1 菌株的转座子突变体库来鉴定 D-半乳聚糖 II 合成基因。删除 wbbY 的肺炎克雷伯菌菌株表现出 D-半乳聚糖 II 生产被取消;改变血清抵抗力和毒力减弱。对肺炎克雷伯菌临床分离株的血清学分析表明,D-半乳聚糖 II 在社区获得性化脓性肝脓肿 (PLA) 引起的菌株中比在非组织侵袭性菌株中更常见。 WbbY 同源物、WbbZ 同源物和基于 D-半乳聚糖 II 的脂多糖结构也存在于几种革兰氏阴性细菌中。用 magA 突变体 (K−1 O1)(即产生 LPS D-半乳聚糖 II 的菌株)对小鼠进行免疫,可提供针对 O1:K2 PLA 菌株感染的保护作用。我们的研究结果表明,WbbY 和 WbbZ 同系物都足以合成 D-半乳聚糖 II。 D-半乳聚糖 II 代表免疫显性抗原;它在多种革兰氏阴性细菌中是保守的,可能是一种有用的候选疫苗。
In the O1 strain of Klebsiella, the lipopolysaccharide (LPS) O-antigen is composed of D-galactan I and D-galactan II. Although the composition of the O1 antigen of Klebsiella was resolved more than two decades, the genetic locus involved in the biosynthesis of D-galactan II and the role of D-galactan II in bacterial pathogenesis remain unclear. Here, we report the identification of the D-galactan II-synthesizing genes by screening a transposon mutant library of an acapsulated Klebsiella pneumoniae O1 strain with bacteriophage. K. pneumoniae strain deleted for wbbY exhibited abrogated D-galactan II production; altered serum resistance and attenuation of virulence. Serologic analysis of K. pneumoniae clinical isolates demonstrated that D-galactan II was more prevalent in community-acquired pyogenic liver abscess (PLA)—causing strains than in non-tissue-invasive strains. WbbY homologs, WbbZ homologs, and lipopolysaccharide structures based on D-galactan II also were present in several Gram-negative bacteria. Immunization of mice with the magA-mutant (K−1 O1) (that is, with a LPS D-galactan II-producing strain) provided protection against infection with an O1:K2 PLA strain. Our findings indicate that both WbbY and WbbZ homologs are sufficient for the synthesis of D-galactan II. D-galactan II represents an immunodominant antigen; is conserved among multiple species of Gram-negative bacteria and could be a useful vaccine candidate.
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