The outer membrane protein A (OmpA) of Yersinia pestis promotes intracellular survival and virulence in mice.

The outer membrane protein A (OmpA) of Yersinia pestis promotes intracellular survival and virulence in mice.
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DOI:
10.1016/j.micpath.2011.09.009
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发表时间:
2012-01
影响因子:
3.8
通讯作者:
Schesser K
Schesser K
中科院分区:
医学3区
文献类型:
--
作者:
Bartra SS;Gong X;Lorica CD;Jain C;Nair MK;Schifferli D;Qian L;Li Z;Plano GV;Schesser K

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鼠疫耶尔森氏菌有许多广为人知的策略来保护自己免受宿主细胞和可溶性因素的影响。为了确定更多的抗宿主因子,我们采用了一种基于转座子位点杂交(Trash)的方法在体外感染系统中筛选105株鼠疫杆菌突变株。除了编码具有良好特性的III型分泌系统(T3SS)的各种成分的基因座外,我们的筛查明确地将OmpA确定为有利于生存的基因。我们继续证明,经过工程改造的鼠疫杆菌ΔOmpA株,以及密切相关的假结核杆菌病原体的ΔOmpA株,具有完全功能的T3SS,但在巨噬细胞内存活方面存在特定缺陷。此外,在小鼠联合感染实验中,鼠疫杆菌ΔompA菌株被野生型菌株击败。与其他细菌病原体中OmpA可以促进黏附、侵袭或血清抵抗不同,鼠疫杆菌的OmpA仅限于提高细胞内的存活。我们的数据表明,致病性耶尔森氏菌的ompA是一个与T3SS相同的毒力因子。
The plague bacterium Yersinia pestis has a number of well-described strategies to protect itself from both host cells and soluble factors. In an effort to identify additional anti-host factors, we employed a transposon site hybridization (TraSH)-based approach to screen 105 Y. pestis mutants in an in vitro infection system. In addition to loci encoding various components of the well-characterized type III secretion system (T3SS), our screen unambiguously identified ompA as a pro-survival gene. We go on to show that an engineered Y. pestis ΔompA strain, as well as a ΔompA strain of the closely related pathogen Y. pseudotuberculosis, have fully functioning T3SSs but are specifically defective in surviving within macrophages. Additionally, the Y. pestis ΔompA strain was outcompeted by the wild-type strain in a mouse co-infection assay. Unlike in other bacterial pathogens in which OmpA can promote adherence, invasion, or serum resistance, the OmpA of Y. pestis is restricted to enhancing intracellular survival. Our data show that OmpA of the pathogenic Yersinia is a virulence factor on par with the T3SS.
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