Jansen Angela M, Lockatell Virginia, Johnson David E, Mobley Harry L T
Department of Microbiology and Immunology, University of Michigan Medical School, 1150 West Medical Center Drive, Ann Arbor, MI 48109-0620, USA.
Infect Immun. 2004 Dec;72(12):7294-305. doi: 10.1128/IAI.72.12.7294-7305.2004.
Proteus mirabilis, an etiologic agent of complicated urinary tract infections, expresses mannose-resistant Proteus-like (MR/P) fimbriae whose expression is phase variable. Here we examine the role of these fimbriae in biofilm formation and colonization of the urinary tract. The majority of wild-type P. mirabilis cells in transurethrally infected mice produced MR/P fimbriae. Mutants that were phase-locked for either constitutive expression (MR/P ON) or the inability to express MR/P fimbriae (MR/P OFF) were phenotypically distinct and swarmed at different rates. The number of P. mirabilis cells adhering to bladder tissue did not appear to be affected by MR/P fimbriation. However, the pattern of adherence to the bladder surface was strikingly different. MR/P OFF colonized the lamina propria underlying exfoliated uroepithelium, while MR/P ON colonized the luminal surfaces of bladder umbrella cells and not the exfoliated regions. Wild-type P. mirabilis was usually found colonizing intact uroepithelium, but it occasionally adhered to exfoliated areas. MR/P ON formed significantly more biofilm than either P. mirabilis HI4320 (P = 0.03) or MR/P OFF (P = 0.05). MR/P OFF was able to form a biofilm similar to that of the wild type. MR/P ON formed a three-dimensional biofilm structure as early as 18 h after the initiation of the biofilm, while MR/P OFF and the wild type did not. After 7 days, however, P. mirabilis HI4320 formed a 65-mum-thick biofilm, while the thickest MR/P ON and MR/P OFF biofilms were only 12 mum thick. We concluded that MR/P fimbriae are expressed by most P. mirabilis cells infecting the urinary tract, dictate the localization of bacteria in the bladder, and contribute to biofilm formation.
奇异变形杆菌是复杂性尿路感染的病原体,可表达甘露糖抗性变形杆菌样(MR/P)菌毛,其表达呈相位可变。在此,我们研究了这些菌毛在生物膜形成和尿路定植中的作用。经尿道感染小鼠的大多数野生型奇异变形杆菌细胞产生MR/P菌毛。组成型表达(MR/P开启)或无法表达MR/P菌毛(MR/P关闭)的相位锁定突变体表型不同,群体游动速率也不同。附着于膀胱组织的奇异变形杆菌细胞数量似乎不受MR/P菌毛形成的影响。然而,其在膀胱表面的附着模式却显著不同。MR/P关闭型定殖于脱落尿路上皮下方的固有层,而MR/P开启型定殖于膀胱伞细胞的腔面而非脱落区域。野生型奇异变形杆菌通常定殖于完整的尿路上皮,但偶尔也会附着于脱落区域。MR/P开启型形成的生物膜明显多于奇异变形杆菌HI4320(P = 0.03)或MR/P关闭型(P = 0.05)。MR/P关闭型能够形成与野生型相似的生物膜。MR/P开启型在生物膜形成开始后18小时就形成了三维生物膜结构,而MR/P关闭型和野生型则没有。然而,7天后,奇异变形杆菌HI4320形成了65微米厚的生物膜,而最厚的MR/P开启型和MR/P关闭型生物膜仅12微米厚。我们得出结论,感染尿路的大多数奇异变形杆菌细胞表达MR/P菌毛,决定细菌在膀胱中的定位,并有助于生物膜形成。