Commonality of Virulence-Promoting Function in Rhodococcus equi Virulence Associated Proteins (Vaps)
Commonality of Virulence-Promoting Function in Rhodococcus equi Virulence Associated Proteins (Vaps)
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DOI：
10.1155/2023/9141112
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发表时间：
2023-10-10
影响因子：
3.4
通讯作者：
Pryor，Paul R.
中科院分区：
文献类型：
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作者：
Ganderton，Timothy R.;Ghete，Daniel;Pryor，Paul R.
马红球菌是一种革兰氏阳性兼性胞内病原体，与马驹中危及生命的支气管肺炎疾病相关。关键是。马在宿主巨噬细胞中的细胞内存活是毒力相关蛋白（Vaps）的产生。在分离自不同物种的毒力质粒上发现了许多Vaps基因，并且Vaps具有高度的序列同一性。VapA基因已被广泛研究，虽然vapK和vapN基因来自其他R.已证明等毒力质粒对R.等胞内存活，它们的作用模式较少被表征。因此，我们研究了VapK和VapN是否以与VapA相同的方式机械地工作。事实上，与VapA一样，VapK和VapN中和了溶酶体pH并降低了溶酶体水解酶活性。VapA和R的损失。VapK或VapN的存在可恢复等毒力。还观察到VapB具有较低程度的酸中和活性。在这些促进毒力的Vaps之间存在差异活性，其中VapN发现的“酸中和”活性最大，然后是VapA和K，最后是VapB。这些数据表明，通常在马感染中发现的VapA产生可以被VapK和B（由通常在猪物种中发现的质粒产生）或VapN（由通常在牛和人样品中分离的质粒产生）取代。这些数据表明，VapA用于中和溶酶体酸性的分子机制也应该在VapN和K中看到，这将有助于指导研究人员确定其精确的作用模式，并有助于靶向治疗的未来发展。
Rhodococcus equiis a Gram‐positive facultative intracellular pathogen associated with life‐threatening bronchopneumonial disease in foals. Key toR. equi’sintracellular survival in host macrophages is the production of virulence associated proteins (Vaps). Numerousvapgenes are found on virulence plasmids isolated from different species, and the Vaps share a high degree of sequence identity. VapA has been extensively studied, and althoughvapKandvapNgenes from otherR. equivirulence plasmids have been shown to be essential forR. equiintracellular survival, their mode of action is less characterised. We, therefore, examined whether VapK and VapN worked mechanistically in the same way as VapA. Indeed, like VapA, VapK and VapN neutralised lysosomal pH and reduced lysosomal hydrolase activity. A loss of VapA andR. equivirulence could be regained by the presence of either VapK or VapN. The acid‐neutralisation activity was also observed to a lesser extent with VapB. There was a differential activity across these virulence‐promoting Vaps with the most “acid‐neutralising” activity found with VapN, then VapA and K, and finally VapB. These data suggest that VapA production, which is often found in equine infections, can be substituted by VapK and B (produced by plasmids often found in porcine species) or VapN (produced by plasmids often isolated in bovine and human samples). These data imply that the molecular mechanism(s) that VapA uses to neutralise lysosomal acidity should also be seen in VapN and K which will help guide researchers in identifying their precise mode of action and aid the future development of targeted therapeutics.