Role of the htrA gene in Klebsiella pneumoniae virulence

Role of the htrA gene in Klebsiella pneumoniae virulence
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DOI:
10.1128/iai.70.9.4772-4776.2002
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发表时间:
2002-09-01
影响因子:
3.1
通讯作者:
Albertí, S
Albertí, S
中科院分区:
医学2区
文献类型:
--
作者:
Cortés, G;de Astorza, B;Albertí, S

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我们最近描述了使用mini-Tn 5来产生来自于脂多糖O侧链缺陷的补体抗性肺炎克雷伯氏菌临床分离株的补体敏感性突变体。一个在非免疫人类血清中生存能力降低的突变体携带插入htrA基因的转座子。我们克隆和测序的基因,并从推导的氨基酸序列预测,推定的HtrA同源物包含类似于先前描述的HtrA蛋白的结构特征。为了研究htrA基因的生物学功能及其在肺炎克雷伯菌毒力中的作用,我们通过插入重复突变法构建了一个htrA基因的同基因突变体。突变株对温度(50 ℃)和氧化胁迫(H2 O2)的敏感性均高于亲本菌株。此外,htrA突变体产生更少的胶囊,结合更多的补体成分C3的分子,并且比亲本菌株对补体和全血杀伤更敏感。最后,在强毒K. pneumoniae菌株引起其在小鼠模型中的毒力降低。这些结果表明,htrA基因在克雷伯氏菌的毒力中起重要作用。肺炎。
We recently described the use of mini-Tn5 to generate complement-sensitive mutants derived from a complement-resistant Klebsiella pneumoniae clinical isolate deficient in the lipopolysaccharide O side chain. One mutant with a reduced capacity to survive in nonimmune human sera carried the transposon inserted in the htrA gene. We cloned and sequenced the gene and predicted from the deduced amino acid sequence that the putative HtrA homolog contains structural features similar to those of previously described HtrA proteins. To investigate the biological functions and the role of the htrA gene in the virulence of X: pneumoniae, we constructed an isogenic mutant by insertion-duplication mutagenesis. Characterization of the mutant showed that it had greater sensitivity to temperature (50degreesC) and oxidative stress (H2O2) than the parent strain. Furthermore, the htrA mutant produced less capsule, bound more molecules of complement component C3, and was more sensitive to complement and whole-blood killing than was the parent strain. Finally, disruption of the htrA gene in a virulent K. pneumoniae strain caused a reduction of its virulence in a mice model. Our results indicate that the htrA gene plays an important role in the virulence of K. pneumoniae.