The type VI secretion system gene cluster of Salmonella typhimurium: Required for full virulence in mice

The type VI secretion system gene cluster of Salmonella typhimurium: Required for full virulence in mice
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鼠伤寒沙门氏菌VI型分泌系统基因簇:对小鼠具有完全毒力所必需的

DOI:
10.1002/jobm.201200047
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发表时间:
2013-07-01
影响因子:
3.1
通讯作者:
Liu, Shu-Lin
Liu, Shu-Lin
中科院分区:
生物学4区
文献类型:
--
作者:
Liu, Ji;Guo, Ji-Tao;Liu, Shu-Lin

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人们越来越多地认为 VI 型分泌系统(T6SS)参与了许多细菌病原体的感染过程,但其在鼠伤寒沙门氏菌毒力中的作用仍不清楚。为了研究这一点,我们从鼠伤寒沙门氏菌 14028s 基因组中删除了 T6SS 簇,并在体外和体内分析了所得的 T6SS 敲除突变体(T6SSKO 突变体)的表型。我们发现,在口服途径感染的 BALB/c 小鼠体内定植竞争模型中,T6SSKO 突变体在脾脏和肝脏中的定植能力降低。此外,通过腹膜内给药的感染还表明,与野生型菌株相比,T6SSKO突变体在小鼠脾脏和肝脏中定殖的能力较差。我们在上皮细胞侵袭测试中没有检测到 T6SSKO 和野生型菌株之间的显着差异。然而,在巨噬细胞RAW264.7细胞系中,T6SSKO突变体的存活率和增殖能力明显低于野生型菌株。这些发现表明,T6SS 基因簇是鼠伤寒沙门氏菌 14028s 在 BALB/c 小鼠中具有完全毒力所必需的,这可能是由于其在巨噬细胞中细菌存活和增殖中的作用。
Type VI secretion system (T6SS) has increasingly been believed to participate in the infection process for many bacterial pathogens, but its role in the virulence of Salmonella typhimurium remains unclear. To look into this, we deleted the T6SS cluster from the genome of S. typhimurium 14028s and analyzed the phenotype of the resulting T6SS knockout mutant (T6SSKO mutant) in vitro and in vivo. We found that the T6SSKO mutant exhibited reduced capability in colonizing the spleen and liver in an in vivo colonization competition model in BALB/ c mice infected by the oral route. Additionally, infection via intraperitoneal administration also showed that the T6SSKO mutant was less capable of colonizing the mouse spleen and liver than the wild-type strain. We did not detect significant differences between the T6SSKO and wild-type strains in epithelial cell invasion tests. However, in the macrophage RAW264.7 cell line, the T6SSKO mutant survived and proliferated significantly more poorly than the wild-type strain. These findings indicate that T6SS gene cluster is required for full virulence of S. typhimurium 14028s in BALB/ c mice, possibly due to its roles in bacterial survival and proliferation in macrophages.