IcgA is a virulence factor of Rhodococcus equi that modulates intracellular growth.
IcgA is a virulence factor of Rhodococcus equi that modulates intracellular growth.
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IcgA 是马红球菌的毒力因子，可调节细胞内生长。
DOI：
10.1128/iai.01670-13
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发表时间：
2014
影响因子：
3.1
通讯作者：
Meijer,WimG
中科院分区：
文献类型：
--
作者：
Wang,Xiaoguang;Coulson,GarryB;Miranda-Casoluengo,AleksandraA;Miranda-Casoluengo,Raúl;Hondalus,MaryK;Meijer,WimG
细胞内病原体马红球菌的毒力取决于位于接合质粒上的21.3 kb致病岛。迄今为止，唯一的非调节性致病岛编码的毒力因子是细胞凋亡相关的VapA蛋白。虽然猪和马的致病力岛。马属分离物中的virRoperon（virR-icgA-vapH-orf 7-virS）基因在两个分离物中高度保守，表明这些基因在致病性中起重要作用。VirR和VirS是控制包括vapA在内的致病岛基因表达的转录调节因子。在这里，我们表明，虽然Handorf 7是对细胞内生长的R。equi，缺失icgA，以前称为asorf 5，编码一个主要的促进剂超家族转运蛋白，引起增强的巨噬细胞的生长表型和巨噬细胞活力的显着降低，而肉汤中的细胞外生长保持不受影响。virS，位于下游的icgA，和vapA的转录没有受到影响theicgA删除在肉汤或巨噬细胞中的生长过程中，显示增强的生长表型所引起的删除icgA不介导通过这些基因的异常转录。转录oficgA增加6倍，在2小时内感染后的巨噬细胞和感染后48小时仍然显着高于感染开始时的水平。主要的易化剂超家族转运蛋白IcgA是在R.对细胞内复制有负面影响的马。除了VapA，它是唯一的第二个致病性岛编码的结构蛋白，显示在这种致病性放线菌的细胞内生长中发挥直接作用。
Virulence of the intracellular pathogen Rhodococcus equi depends on a 21.3-kb pathogenicity island located on a conjugative plasmid. To date, the only nonregulatory pathogenicity island-encoded virulence factor identified is the cell envelope-associated VapA protein. Although the pathogenicity islands from porcine and equine R. equi isolates have undergone major rearrangements, thevirRoperon (virR-icgA-vapH-orf7-virS) is highly conserved in both, suggesting these genes play an important role in pathogenicity. VirR and VirS are transcriptional regulators controlling expression of pathogenicity island genes, includingvapA. Here, we show that whilevapHandorf7are dispensable for intracellular growth of R. equi, deletion oficgA, formerly known asorf5, encoding a major facilitator superfamily transport protein, elicited an enhanced growth phenotype in macrophages and a significant reduction in macrophage viability, while extracellular growth in broth remained unaffected. Transcription ofvirS, located downstream oficgA, andvapAwas not affected by theicgAdeletion during growth in broth or in macrophages, showing that the enhanced growth phenotype caused by deletion oficgAwas not mediated through abnormal transcription of these genes. Transcription oficgAincreased 6-fold within 2 h following infection of macrophages and remained significantly higher 48 h postinfection compared to levels at the start of the infection. The major facilitator superfamily transport protein IcgA is the first factor identified in R. equi that negatively affects intracellular replication. Aside from VapA, it is only the second pathogenicity island-encoded structural protein shown to play a direct role in intracellular growth of this pathogenic actinomycete.