Department of Medicine, Section of Infectious Diseases.
Infect Immun. 2013 Oct;81(10):3652-61. doi: 10.1128/IAI.00298-13. Epub 2013 Jul 22.
Neisseria gonorrhoeae, the causative agent of the sexually transmitted disease gonorrhea, can infect and colonize multiple mucosal sites in both men and women. The ability to cope with different environmental conditions requires tight regulation of gene expression. In this study, we identified and characterized a gonococcal transcriptional regulatory protein (Neisseria phage repressor [Npr]) that was previously annotated as a putative gonococcal phage repressor protein. Npr was found to repress transcription of NGNG_00460 to NGNG_00463 (NGNG_00460-00463), an operon present within the phage locus NgoΦ4. Npr binding sites within the NGNG_00460-00463 promoter region were found to overlap the -10 and -35 promoter motifs. A gonococcal npr mutant demonstrated increased adherence to and invasion of human endocervical epithelial cells compared to a wild-type gonococcal strain. Likewise, the gonococcal npr mutant exhibited enhanced colonization in a gonococcal mouse model of mucosal infection. Analysis of the gonococcal npr mutant using RNA sequence (RNA-seq) analysis demonstrated that the Npr regulon is limited to the operon present within the phage locus. Collectively, our studies have defined a new gonococcal phage repressor protein that controls the transcription of genes implicated in gonococcal pathogenesis.
淋病奈瑟菌是性传播疾病淋病的病原体，能够感染和定植于男性和女性的多个黏膜部位。为了适应不同的环境条件，淋病奈瑟菌需要对基因表达进行严格调控。在本研究中，我们鉴定并表征了一种淋病奈瑟菌转录调控蛋白（Neisseria phage repressor [Npr]），该蛋白先前被注释为一种假定的淋病奈瑟菌噬菌体 repressor 蛋白。研究发现，Npr 能够抑制 NGNG_00460 至 NGNG_00463（NGNG_00460-00463）的转录，该操纵子位于噬菌体 locus NgoΦ4 内。在 NGNG_00460-00463 启动子区域内发现的 Npr 结合位点与-10 和-35 启动子基序重叠。与野生型淋病奈瑟菌菌株相比，淋病奈瑟菌 npr 突变体对人宫颈内上皮细胞的黏附和侵袭能力增强。同样，淋病奈瑟菌 npr 突变体在淋病奈瑟菌黏膜感染的小鼠模型中表现出更强的定植能力。使用 RNA 序列（RNA-seq）分析对淋病奈瑟菌 npr 突变体进行分析表明，Npr 调控子仅限于噬菌体 locus 内的操纵子。总之，我们的研究定义了一种新的淋病奈瑟菌噬菌体 repressor 蛋白，该蛋白控制与淋病奈瑟菌发病机制相关基因的转录。
