Jones Brian V, Young Robert, Mahenthiralingam Eshwar, Stickler David J
Cardiff School of Biosciences, Cardiff University, Main Bldg., Rm. 1.53, Cardiff, Wales, United Kingdom CF10 3TL.
Infect Immun. 2004 Jul;72(7):3941-50. doi: 10.1128/IAI.72.7.3941-3950.2004.
Proteus mirabilis is a common cause of catheter-associated urinary tract infection (C-UTI). It blocks indwelling urethral catheters through the formation of extensive crystalline biofilms. The obstruction of urine flow can induce episodes of pyelonephritis, septicemia, and shock. P. mirabilis exhibits a type of motility referred to as swarming, in which multicellular rafts of elongated, hyperflagellated swarmer cells form and move rapidly in concert over solid surfaces. It has been suggested that swarming is important in the pathogenesis of C-UTI. In this study we generated a set of stable transposon mutants deficient in swarming and used them to assess the role of swarming in the migration of P. mirabilis over urinary catheters. Swarming was found to be essential for migration over all-silicone catheters. Swarming-deficient mutants were attenuated in migration over hydrogel-coated latex catheters, but those capable of swimming motility were able to move over and infect these surfaces. A novel vapor fixation technique for the preparation of specimens and scanning electron microscopy were used to resolve the ultrastructure of P. mirabilis multicellular rafts. The flagellar filaments of P. mirabilis were found to be highly organized during raft migration and were interwoven in phase to form helical connections between adjacent swarmer cells. Mutants lacking these novel organized structures failed to swarm successfully. We suggest that these structures are important for migration and formation of multicellular rafts. In addition, the highly organized structure of multicellular rafts enables P. mirabilis to initiate C-UTI by migration over catheter surfaces from the urethral meatus into the bladder.
奇异变形杆菌是导管相关尿路感染(C-UTI)的常见病因。它通过形成广泛的结晶生物膜来阻塞留置尿道导管。尿液流动受阻可引发肾盂肾炎、败血症和休克。奇异变形杆菌表现出一种称为群游的运动方式,其中细长的、多鞭毛的游动细胞形成多细胞筏,并在固体表面上协同快速移动。有人认为群游在C-UTI的发病机制中很重要。在本研究中,我们构建了一组缺乏群游能力的稳定转座子突变体,并利用它们来评估群游在奇异变形杆菌在导尿管上迁移中的作用。结果发现群游对于在全硅胶导管上的迁移至关重要。缺乏群游能力的突变体在水凝胶涂层乳胶导管上的迁移能力减弱,但那些具有游泳运动能力的突变体能够在这些表面上移动并感染。一种用于制备标本的新型蒸汽固定技术和扫描电子显微镜被用于解析奇异变形杆菌多细胞筏的超微结构。发现在筏迁移过程中,奇异变形杆菌的鞭毛丝高度有序,并相互交织形成相邻游动细胞之间的螺旋连接。缺乏这些新型有序结构的突变体无法成功群游。我们认为这些结构对于多细胞筏的迁移和形成很重要。此外,多细胞筏的高度有序结构使奇异变形杆菌能够通过从尿道口在导管表面迁移到膀胱来引发C-UTI。