The Tol-Pal System of Uropathogenic Escherichia coli Is Responsible for Optimal Internalization Into and Aggregation Within Bladder Epithelial Cells, Colonization of the Urinary Tract of Mice, and Bacterial Motility
The Tol-Pal System of Uropathogenic Escherichia coli Is Responsible for Optimal Internalization Into and Aggregation Within Bladder Epithelial Cells, Colonization of the Urinary Tract of Mice, and Bacterial Motility
复制标题
DOI：
10.3389/fmicb.2019.01827
复制
发表时间：
2019-08-07
影响因子：
5.2
通讯作者：
Tomita, Haruyoshi
中科院分区：
文献类型：
--
作者：
Hirakawa, Hidetada;Suzue, Kazutomo;Tomita, Haruyoshi
尿路感染是由尿路致病性大肠埃希菌（UPEC）引起的一种常见的传染病。随着新的抗微生物剂的短缺，UPEC对常用药物如氟喹诺酮类和β-内酰胺类（包括碳青霉烯类）的耐药性增加是一个关键问题。UPEC侵入泌尿道细胞，在那里它聚集，随后形成生物膜样多细胞菌落，称为细胞内细菌群落（IBC）。这个过程允许细菌建立感染，因此可能是治疗感染的新药的良好潜在靶点。在这里，我们表明，删除的tolB基因，编码的蛋白质的Tol-peptide系统，最初的特点是作为一个蛋白质复合物的大肠杆菌素的摄取和维护外膜，降低水平的细菌内化和聚集在培养的膀胱上皮细胞内，也抑制小鼠尿路的定植。tolB突变体也表现出有缺陷的运动，因为受损的鞭毛合成。fliC和motA突变体是非运动菌株，也表现出比其野生型亲本更低的细菌内化和聚集水平。fliC突变体中tolB的额外缺失没有进一步降低这些，表明tolB突变体的毒力减弱是运动缺陷的结果。缺乏Tol-fos系统的其他成员的托拉、tolQ、tolR和pal突变体与其野生型亲本相比也表现出膀胱上皮细胞内较低水平的运动性和聚集性。这些综合结果表明了Tol-Glutamine系统的另一个作用，即，它负责最佳内化、聚集，随后在尿路细胞内形成IBC，以及细菌运动。
Urinary tracts infection (UTI) caused by uropathogenic Escherichia coli (UPEC) is a common infectious disease. With the shortage of new antimicrobial agents, the increase in UPEC resistance to commonly used drugs, such as fluoroquinolones and beta-lactams including carbapenems is a critical issue. UPEC invades urinary tract cells, where it aggregates, and subsequently, forms biofilm-like multicellular colonies termed intracellular bacterial communities (IBCs). This process allows the bacteria to establish infections and so may be a good potential target for new drugs to treat infections. Here, we show that deletion of the tolB gene, encoding a protein of the Tol-Pal system that was originally characterized as a protein complex for colicin uptake and maintenance of the outer membrane, decreases the level of bacterial internalization into and aggregation within cultured bladder epithelial cells and also inhibits the colonization of mice urinary tracts. The tolB mutant also exhibited defective motility because of impaired flagellum syntheses. The fliC and motA mutants, which are non-motile strains, also exhibited lower levels of bacterial internalization and aggregation than their wild-type parent. Additional deletion of tolB in the fliC mutant did not further decrease these, suggesting that the attenuated virulence of the tolB mutant is a result of defective motility. The tolA, tolQ, tolR, and pal mutants that lack other members of the Tol-Pal system also exhibited lower levels of motility and aggregation within bladder epithelial cells compared to their wild-type parent. These combined results suggest another role of the Tol-Pal system, i.e., that it is responsible for optimal internalization, aggregation followed by IBC formation within urinary tract cells, and bacterial motility.