A novel virulence gene in Klebsiella pneumoniae strains causing primary liver abscess and septic metastatic complications.

A novel virulence gene in Klebsiella pneumoniae strains causing primary liver abscess and septic metastatic complications.
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DOI:
10.1084/jem.20030857
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发表时间:
2004-03-01
影响因子:
15.3
通讯作者:
Wang, JT
Wang, JT
中科院分区:
医学1区
文献类型:
--
作者:
Fang, CT;Chuang, YP;Shun, CT;Chang, SC;Wang, JT

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原发性肺炎克雷伯菌肝脓肿合并转移性脑膜炎或眼内炎是一种全球性的新发传染病。其致病机制尚不清楚。通过比较临床分离株,探讨细菌毒力因子。在引起原发性肝脓肿(侵入性)和不引起原发性肝脓肿(非侵入性)的菌株之间观察到粘液粘度的差异。高粘液粘度与高血清抵抗相关,在侵袭性菌株中更常见(52/53 vs. 9/52; P < 0.0001)。转座子诱变鉴定了候选毒力基因。一个新的1.2 kb基因座,magA,编码一个43 kD的外膜蛋白,在侵袭性菌株中明显更普遍(52/53比14/52; P < 0.0001)。野生型菌株产生一个粘粘的胞外多糖网,在非免疫的人血清中活跃增殖,抵抗吞噬作用,并引起小鼠肝微脓肿和脑膜炎。然而,magA −突变体失去了胞外多糖网,变得对血清非常敏感,对吞噬作用敏感,对小鼠无毒。通过使用含有magA的质粒进行互补来恢复毒力。我们的结论是,magA符合分子科赫的假设作为一个毒力基因。因此,该位点可用作快速诊断和追踪这种新兴传染病来源的标记。
Primary Klebsiella pneumoniae liver abscess complicated with metastatic meningitis or endophthalmitis is a globally emerging infectious disease. Its pathogenic mechanism remains unclear. The bacterial virulence factors were explored by comparing clinical isolates. Differences in mucoviscosity were observed between strains that caused primary liver abscess (invasive) and those that did not (noninvasive). Hypermucoviscosity correlated with a high serum resistance and was more prevalent in invasive strains (52/53 vs. 9/52; P < 0.0001). Transposon mutagenesis identified candidate virulence genes. A novel 1.2-kb locus, magA, which encoded a 43-kD outer membrane protein, was significantly more prevalent in invasive strains (52/53 vs. 14/52; P < 0.0001). The wild-type strain produced a mucoviscous exopolysaccharide web, actively proliferated in nonimmune human serum, resisted phagocytosis, and caused liver microabscess and meningitis in mice. However, magA − mutants lost the exopolysaccharide web and became extremely serum sensitive, phagocytosis susceptible, and avirulent to mice. Virulence was restored by complementation using a magA-containing plasmid. We conclude that magA fits molecular Koch's postulates as a virulence gene. Thus, this locus can be used as a marker for the rapid diagnosis and for tracing the source of this emerging infectious disease.
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