Bartonella henselae (Bh) is a Gram-negative zoonotic bacterium that can grow as large aggregates and form biofilms in vitro dependent upon the adhesin BadA. Previously, we reported that the Houston-1 strain of Bh has a family of nine small, highly-expressed intergenic transcripts called Bartonella regulatory transcripts, Brt1-9. Each of the Brts bears a stem and loop structure on the 3′ end followed by a gene encoding a DNA binding protein called the Transcriptional regulatory proteins, Trp1-9. RNA-seq analysis of laboratory-grown bacteria revealed the trps were poorly transcribed suggesting that the 3′ stem and loop on the Brts results in transcript termination upstream of the trp genes under these conditions. Here we demonstrate that transcription of brt1 continues into trp1 when Bh is grown in a biofilm. Deletion of brt1, or just the 3′ terminus of brt1 (containing the stem and loop structure), resulted in increased transcription of both trp1 and badA and increased biofilm formation. Trp1 was shown to directly bind the putative badA promoter region as demonstrated by an electrophoretic mobility shift assay (EMSA). Our data suggest that the 3′ end of brt1 responds to a stimulus generated by growth of Bh in an in vitro biofilm to allow increased trp1 transcription. We further show that transcription of trp1 increases under conditions consistent with the mammalian host but is not highly expressed in the cat flea vector until the bacterium is excreted into the flea feces. Based on these data, we hypothesize that the 3’ end of Brt1 functions to control trp1 transcription and Trp1 in turn results in increased badA expression and enhanced biofilm formation.

亨氏巴尔通体（Bh）是革兰氏阴性的人畜共患细菌，可生长成大的聚集体，并在体外依赖粘附素BadA形成生物膜。此前，我们报道了休斯敦-1株了Bh有一户人家叫九小，高表达基因间的转录乙artonella [R egulatory牛逼ranscripts，Brt1-9。每个BRTS的支承在3'端的茎和环结构，接着通过编码称为DNA结合蛋白的基因Ť ranscriptional ř egulatory p roteins，Trp1-9。实验室培养细菌的RNA序列分析显示trps转录较差，表明在这些条件下，Brts上的3'茎和环导致trp基因上游的转录终止。在这里，我们证明了Bh在生物膜中生长时，brt1的转录继续进入trp1。的缺失BRT1，或只是3'末端的BRT1号（含有茎和环结构），导致增加的两者的转录TRP1和八达和增加的生物膜形成。显示Trp1直接结合假定的badA电泳迁移率变动分析（EMSA）所证实的启动子区域。我们的数据表明，brt1的3'端对体外生物膜中Bh的生长所产生的刺激作出反应，从而使trp1转录增加。我们进一步显示，在与哺乳动物宿主一致的条件下，trp1的转录增加，但在猫蚤载体中并未高度表达，直到细菌被排泄到蚤粪中。基于这些数据，我们假设Brt1的3'端起到控制trp1转录和Trp1的作用，进而导致badA表达增加和生物膜形成增强。