Many pathogenic bacteria translocate virulence factors into their eukaryotic hosts by means of type IV secretion systems (T4SS) spanning the inner and outer membranes. Genes encoding components of these systems have been identified within the order Rickettsiales based upon their sequence similarities to other prototypical systems. Anaplasma phagocytophilum strains are obligate intracellular, tick-borne bacteria that are members of this order. The organization of these components at the genomic level was determined in several Anaplasma phagocytophilum strains, showing overall conservation, with the exceptions of the virB2 and virB6 genes. The virB6 loci are characterized by the presence of four virB6 copies (virB6-1 through virB6-4) arranged in tandem within a gene cluster known as the sodB-virB operon. Interestingly, the virB6-4 gene varies significantly in length among different strains due to extensive tandem repeats at the 3′ end. To gain an understanding of how these enigmatic virB6 genes function in A. phagocytophilum, we investigated their expression in infected human and tick cells. Our results show that these genes are expressed by A. phagocytophilum replicating in both cell types and that VirB6-3 and VirB6-4 proteins are surface exposed. Analysis of an A. phagocytophilum mutant carrying the Himar1 transposon within the virB6-4 gene demonstrated that the insertion not only disrupted its expression but also exerted a polar effect on the sodB-virB operon. Moreover, the altered expression of genes within this operon was associated with the attenuated in vitro growth of A. phagocytophilum in human and tick cells, indicating the importance of these genes in the physiology of this obligate intracellular bacterium in such different environments.

中文翻译：

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吞噬嗜浆细胞中VirB6旁系同源物的破坏减弱了其生长。

许多病原细菌通过跨越内膜和外膜的IV型分泌系统（T4SS）将毒力因子转运到其真核宿主中。已根据立克次体与其他原型系统的序列相似性，在立克次体中鉴定了编码这些系统组件的基因。嗜无浆细胞嗜性菌菌株是专属于此顺序的细胞内，传播细菌。这些成分在基因组水平的组织在几个确定的无形体吞噬细胞株，显示出整体保护，用的例外virB2和virB6基因。该virB6基因座的特征是存在四个virB6拷贝（virB6-1至virB6-4），这些拷贝串联排列在一个称为sodB-virB操纵子的基因簇内。有趣的是，由于在3'端广泛的串联重复，virB6-4基因在不同菌株之间的长度差异很大。为了获得这些神秘如何理解virB6基因在发挥作用A.吞噬细胞，我们研究了感染的人并勾选细胞中的表达。我们的研究结果表明，这些基因在两种细胞类型中均由吞噬链球菌复制表达，并且VirB6-3和VirB6-4蛋白表面暴露。分析A.吞噬细胞的突变体携带有内Himar1座子virB6-4基因证实了插入不仅破坏它的表达，而且施加在极性效应SODB-VIR乙操纵子。此外，该操纵子中基因表达的改变与人类和壁虱细胞中嗜吞噬菌的体外生长减慢有关，表明这些基因在这种专性细胞内细菌在这种不同环境中的生理作用很重要。