Lane M Chelsea, Lockatell Virginia, Monterosso Greta, Lamphier Daniel, Weinert Julia, Hebel J Richard, Johnson David E, Mobley Harry L T
Department of Microbiology and Immunology, University of Michigan Medical School, 5641 Medical Science Building II, 1150 West Medical Center Drive, Ann Arbor, MI 48109, USA.
Infect Immun. 2005 Nov;73(11):7644-56. doi: 10.1128/IAI.73.11.7644-7656.2005.
Uropathogenic Escherichia coli (UPEC) causes most uncomplicated urinary tract infections (UTIs) in humans. Flagellum-mediated motility and chemotaxis have been suggested to contribute to virulence by enabling UPEC to escape host immune responses and disperse to new sites within the urinary tract. To evaluate their contribution to virulence, six separate flagellar mutations were constructed in UPEC strain CFT073. The mutants constructed were shown to have four different flagellar phenotypes: fliA and fliC mutants do not produce flagella; the flgM mutant has similar levels of extracellular flagellin as the wild type but exhibits less motility than the wild type; the motAB mutant is nonmotile; and the cheW and cheY mutants are motile but nonchemotactic. Virulence was assessed by transurethral independent challenges and cochallenges of CBA mice with the wild type and each mutant. CFU/ml of urine or CFU/g bladder or kidney was determined 3 days postinoculation for the independent challenges and at 6, 16, 48, 60, and 72 h postinoculation for the cochallenges. While these mutants colonized the urinary tract during independent challenge, each of the mutants was outcompeted by the wild-type strain to various degrees at specific time points during cochallenge. Altogether, these results suggest that flagella and flagellum-mediated motility/chemotaxis may not be absolutely required for virulence but that these traits contribute to the fitness of UPEC and therefore significantly enhance the pathogenesis of UTIs caused by UPEC.
尿路致病性大肠杆菌(UPEC)可引发人类大多数非复杂性尿路感染(UTIs)。鞭毛介导的运动性和趋化性被认为有助于UPEC的毒力,因为它们能使UPEC逃避宿主免疫反应并扩散至尿路内的新部位。为评估它们对毒力的作用,在UPEC菌株CFT073中构建了六个单独的鞭毛突变体。构建的突变体显示出四种不同的鞭毛表型:fliA和fliC突变体不产生鞭毛;flgM突变体的细胞外鞭毛蛋白水平与野生型相似,但运动性低于野生型;motAB突变体不运动;cheW和cheY突变体可运动但无趋化性。通过经尿道独立攻击以及将野生型和每个突变体与CBA小鼠共同攻击来评估毒力。对于独立攻击,在接种后3天测定尿液中的CFU/ml或膀胱或肾脏中的CFU/g;对于共同攻击,在接种后6、16、48、60和72小时测定。虽然这些突变体在独立攻击期间可在尿路中定殖,但在共同攻击的特定时间点,每个突变体都在不同程度上被野生型菌株击败。总之,这些结果表明,鞭毛以及鞭毛介导的运动性/趋化性可能并非毒力所绝对必需,但这些特性有助于UPEC的适应性,因此显著增强了由UPEC引起的UTIs的发病机制。