Buckles Eric L, Wang Xiaolin, Lane M Chelsea, Lockatell C Virginia, Johnson David E, Rasko David A, Mobley Harry L T, Donnenberg Michael S
Department of Medicine, University of Maryland School of Medicine, MD, USA.
J Infect Dis. 2009 Jun 1;199(11):1689-97. doi: 10.1086/598524.
Capsule expression may be important during ascending Escherichia coli urinary tract infections (UTIs).
An isogenic ksl(k2)ABCDE mutant of extraintestinal pathogenic E. coli (ExPEC) strain CFT073 that could not synthesize the K2 capsule was compared with wild-type CFT073, to determine virulence in a murine model of ascending UTI and in vitro killing assays.
No significant differences were observed regarding the abilities of the mutant and the wild-type CFT073 strains to colonize the murine urinary tract in single-challenge infection experiments. However, in competitive-colonization experiments, the mutant was significantly outcompeted by the wild-type strain in urine and the kidneys. The mutant strain was also more susceptible to human serum. Complementation of the mutant with a plasmid containing the ksl(k2)ABCDE genes restored capsule expression, enhanced survival in the murine urinary tract, and restored serum resistance.
These results indicate that expression of the K2 capsule is important for the pathogenesis of UTI and provides protection against complement-mediated killing. To our knowledge, this is the first study in which the E. coli capsule has been proven to play a role in infection by use of isogenic mutants and genetic complementation.
在大肠埃希菌上行性尿路感染(UTIs)过程中,荚膜表达可能很重要。
将不能合成K2荚膜的肠道外致病性大肠埃希菌(ExPEC)菌株CFT073的同基因ksl(k2)ABCDE突变体与野生型CFT073进行比较,以确定其在小鼠上行性UTI模型和体外杀伤试验中的毒力。
在单次攻击感染实验中,突变体和野生型CFT073菌株在定殖于小鼠泌尿道的能力方面未观察到显著差异。然而,在竞争性定殖实验中,突变体在尿液和肾脏中被野生型菌株显著竞争淘汰。突变菌株对人血清也更敏感。用含有ksl(k2)ABCDE基因的质粒对突变体进行互补,可恢复荚膜表达,增强在小鼠泌尿道中的存活能力,并恢复血清抗性。
这些结果表明,K2荚膜的表达对UTI的发病机制很重要,并提供了针对补体介导杀伤的保护作用。据我们所知,这是第一项通过使用同基因突变体和基因互补证明大肠埃希菌荚膜在感染中起作用的研究。