VapA of Rhodococcus equi binds phosphatidic acid.
VapA of Rhodococcus equi binds phosphatidic acid.
复制标题
Rhodococcus Equi的VAPA结合磷脂酸。
DOI：
10.1111/mmi.13892
复制
发表时间：
2018-03
影响因子：
3.6
通讯作者：
Starai VJ
中科院分区：
文献类型：
--
作者：
Wright LM;Carpinone EM;Bennett TL;Hondalus MK;Starai VJ
马红球菌是一种多宿主、兼性细胞内细菌病原体，主要引起小于6个月龄的马驹和免疫功能低下的人的肺炎。以往的研究表明，该菌的主要毒力决定因子是一种新的致病菌。Equi是表面结合毒力相关蛋白A（VapA）。VapA的存在抑制了R. equi-含有吞噬体和促进细胞内细菌存活，如通过vapA缺失突变体不能在宿主巨噬细胞中复制所确定的。虽然VapA的作用机制仍然难以捉摸，但我们发现可溶性重组VapA 32 -189既能挽救野生型R.马属菌株缺乏vapA基因，并增强非致病性大肠杆菌在巨噬细胞中的持久性。在巨噬细胞感染期间，在细菌表面和宿主来源的R.含有马的液泡，从而为VapA提供了与宿主成分相互作用并促进吞噬溶酶体功能改变的机会。为了支持观察到的VapA的宿主膜结合活性，我们还发现rVapA 32 -189在体外与含有磷脂酸的脂质体特异性相互作用。总的来说，这些数据证明了VapA的脂质结合特性，这可能是其在细胞内感染期间发挥功能所必需的。毒力相关蛋白A（VapA），细胞内病原体马红球菌的一个关键毒力决定因素，观察到改变巨噬细胞的杀伤能力和本地化的真核细胞膜在感染过程中。证明了重组VapA蛋白与含有磷脂酸的脂质体的直接结合。
Rhodococcus equi is a multi-host, facultative intracellular bacterial pathogen that primarily causes pneumonia in foals less than six months in age and immunocompromised people. Previous studies determined that the major virulence determinant of R. equi is the surface bound virulence associated protein A (VapA). The presence of VapA inhibits the maturation of R. equi-containing phagosomes and promotes intracellular bacterial survival, as determined by the inability of vapA deletion mutants to replicate in host macrophages. While the mechanism of action of VapA remains elusive, we show that soluble recombinant VapA32-189 both rescues the intramacrophage replication defect of a wild type R. equi strain lacking the vapA gene and enhances the persistence of nonpathogenic Escherichia coli in macrophages. During macrophage infection, VapA was observed at both the bacterial surface and at the membrane of the host-derived R. equi containing vacuole, thus providing an opportunity for VapA to interact with host constituents and promote alterations in phagolysosomal function. In support of the observed host membrane binding activity of VapA, we also found that rVapA32-189 interacted specifically with liposomes containing phosphatidic acid in vitro. Collectively, these data demonstrate a lipid binding property of VapA, which may be required for its function during intracellular infection. Virulence associated protein A (VapA), a key virulence determinant of the intracellular pathogen Rhodococcus equi, was observed to alter macrophage killing capacity and localize to eukaryotic membranes during infection. Direct binding of recombinant VapA protein to liposomes containing phosphatidic acid was demonstrated.
登录
查看更多内容
影响因子：
3.3
作者：
Burton, Alexandra J.;Giguere, Steeve;Arnold, Robert D.
通讯作者：
Arnold, Robert D.
影响因子：
56.9
作者：
Fang, YM;Vilella-Bach, M;Chen, J
通讯作者：
Chen, J
影响因子：
3.1
作者：
Coulson, Garry B.;Agarwal, Shruti;Hondalus, Mary K.
通讯作者：
Hondalus, Mary K.
影响因子：
3.3
作者：
Flynn, O;Quigley, F;Takai, S
通讯作者：
Takai, S
影响因子：
4.8
作者：
Frondorf, Kathleen;Henkels, Karen M.;Gomez-Cambronero, Julian
通讯作者：
Gomez-Cambronero, Julian