A Putative Regulatory Genetic Locus Modulates Virulence in the Pathogen Leptospira interrogans
A Putative Regulatory Genetic Locus Modulates Virulence in the Pathogen Leptospira interrogans
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DOI：
10.1128/iai.01803-14
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发表时间：
2014-06-01
影响因子：
3.1
通讯作者：
Picardeau, Mathieu
中科院分区：
文献类型：
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作者：
Eshghi, Azad;Becam, Jerome;Picardeau, Mathieu
有限的研究已经进行了转录调节因子的作用，毒力相关的钩端螺旋体，钩体病的病原体。在这里，我们确定一个L。问号基因座，其编码传感器蛋白、抗σ因子拮抗剂和两个编码未知功能蛋白的基因。将转座子插入到编码传感蛋白的基因中导致该基因座中其他3个基因的转录受到抑制。这种lb 139插入突变体（lb 139（-）突变体）在仓鼠感染模型中表现出减弱的毒力，并在体外降低了运动性。使用RNA测序的全转录组分析揭示了115个基因的下调和28个基因的上调，具有运动和信号转导功能的基因产物和许多功能未知的基因产物的过度表达，预测定位于细胞外空间。另一个重要的发现包括抑制大多数基因的表达，这些基因先前被证明在生理渗透压下上调，包括鞘磷脂酶C前体Sph 2和LigB。我们提供了一个可能的要求，转录调控，因为它涉及到钩端螺旋体毒力的洞察，并建议各种生物过程的影响，由于本机表达的这个遗传位点的损失。
Limited research has been conducted on the role of transcriptional regulators in relation to virulence in Leptospira interrogans, the etiological agent of leptospirosis. Here, we identify an L. interrogans locus that encodes a sensor protein, an anti-sigma factor antagonist, and two genes encoding proteins of unknown function. Transposon insertion into the gene encoding the sensor protein led to dampened transcription of the other 3 genes in this locus. This lb139 insertion mutant (the lb139(-) mutant) displayed attenuated virulence in the hamster model of infection and reduced motility in vitro. Whole-transcriptome analyses using RNA sequencing revealed the downregulation of 115 genes and the upregulation of 28 genes, with an overrepresentation of gene products functioning in motility and signal transduction and numerous gene products with unknown functions, predicted to be localized to the extracellular space. Another significant finding encompassed suppressed expression of the majority of the genes previously demonstrated to be upregulated at physiological osmolarity, including the sphingomyelinase C precursor Sph2 and LigB. We provide insight into a possible requirement for transcriptional regulation as it relates to leptospiral virulence and suggest various biological processes that are affected due to the loss of native expression of this genetic locus.