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致病性岛蛋白PdpA的特性及其在新凶手弗朗西斯菌毒力中的作用。

Characterization of the pathogenicity island protein PdpA and its role in the virulence of Francisella novicida.

作者信息

Schmerk Crystal L, Duplantis Barry N, Wang Diana, Burke Robert D, Chou Alicia Y, Elkins Karen L, Ludu Jagjit S, Nano Francis E

机构信息

Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC, Canada.

Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, MD, USA.

出版信息

Microbiology (Reading). 2009 May;155(Pt 5):1489-1497. doi: 10.1099/mic.0.025379-0. Epub 2009 Apr 16.

Abstract

Francisella tularensis is a highly virulent, intracellular pathogen that causes the disease tularaemia. A research surrogate for F. tularensis is Francisella novicida, which causes a tularaemia-like disease in mice, grows similarly in macrophages, and yet is unable to cause disease in humans. Both Francisella species contain a cluster of genes referred to as the Francisella pathogenicity island (FPI). Pathogenicity determinant protein A (PdpA), encoded by the pdpA gene, is located within the FPI and has been associated with the virulence of Francisella species. In this work we examined the properties of PdpA protein expression and localization as well as the phenotype of a F. novicida pdpA deletion mutant. Monoclonal antibody detection of PdpA showed that it is a soluble protein that is upregulated in iron-limiting conditions and undetectable in an mglA or mglB mutant background. Deletion of pdpA resulted in a strain that was highly attenuated for virulence in chicken embryos and mice.

摘要

土拉弗朗西斯菌是一种高致病性的细胞内病原体,可引发兔热病。诺维奇弗朗西斯菌是土拉弗朗西斯菌的一种研究替代物,它能在小鼠中引发类似兔热病的疾病,在巨噬细胞中的生长情况相似,但无法在人类中致病。这两种弗朗西斯菌都含有一组被称为弗朗西斯菌致病岛(FPI)的基因。由pdpA基因编码的致病性决定蛋白A(PdpA)位于FPI内,并且与弗朗西斯菌的毒力相关。在这项研究中,我们检测了PdpA蛋白的表达和定位特性,以及诺维奇弗朗西斯菌pdpA缺失突变体的表型。对PdpA的单克隆抗体检测表明,它是一种可溶性蛋白,在铁限制条件下上调,在mglA或mglB突变背景中无法检测到。pdpA的缺失导致菌株在鸡胚和小鼠中的毒力大幅减弱。

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本文引用的文献

1
A Francisella novicida pdpA mutant exhibits limited intracellular replication and remains associated with the lysosomal marker LAMP-1.
Microbiology (Reading). 2009 May;155(Pt 5):1498-1504. doi: 10.1099/mic.0.025445-0. Epub 2009 Apr 16.
2
Identification of fevR, a novel regulator of virulence gene expression in Francisella novicida.
Infect Immun. 2008 Aug;76(8):3473-80. doi: 10.1128/IAI.00430-08. Epub 2008 Jun 16.
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Secretome analysis uncovers an Hcp-family protein secreted via a type VI secretion system in Agrobacterium tumefaciens.
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