Zunino Pablo, Sosa Vanessa, Schlapp Geraldine, Allen Andrew G, Preston Andrew, Maskell Duncan J
Laboratorio de Microbiología, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay.
FEMS Immunol Med Microbiol. 2007 Oct;51(1):125-33. doi: 10.1111/j.1574-695X.2007.00285.x.
Proteus mirabilis is an important uropathogen that can cause complicated urinary tract infections (UTI). It produces several types of fimbriae, including mannose-resistant Proteus-like (MR/P) fimbriae and P. mirabilis fimbriae (PMF). Previously, we determined that these fimbriae affect the ability of P. mirabilis to colonize the urinary tract. The objective of this study was to analyse the effect of the simultaneous lack of P. mirabilis MR/P and PMF fimbriae in UTI pathogenesis. A double mutant lacking both fimbriae was generated by allelic replacement mutagenesis. This mutant was characterized genetically and phenotypically, and tested using an in vitro uroepithelial cell adhesion assay and the ascending UTI murine model. In vitro adhesion to uroepithelial cells by the P. mirabilis pmfA/mrpA-D mutant was reduced when compared with the wild-type, although no significant differences were observed when it was compared with the single mrpA-D and pmfA mutants. However, in vivo assays showed that colonization of kidneys and bladders by the P. mirabilis pmfA/mrpA-D mutant was significantly reduced when compared with the wild-type and both single mutants. These results indicate that, although redundancy can occur, MR/P and PMF fimbriae have specific and additive roles in P. mirabilis UTI.
奇异变形杆菌是一种重要的尿路致病菌,可引起复杂性尿路感染(UTI)。它能产生几种类型的菌毛,包括甘露糖抗性变形杆菌样(MR/P)菌毛和奇异变形杆菌菌毛(PMF)。此前,我们已确定这些菌毛会影响奇异变形杆菌在尿路中定殖的能力。本研究的目的是分析同时缺失奇异变形杆菌MR/P和PMF菌毛对UTI发病机制的影响。通过等位基因置换诱变产生了一种同时缺失这两种菌毛的双突变体。对该突变体进行了遗传和表型特征分析,并使用体外尿路上皮细胞黏附试验和上行性UTI小鼠模型进行了测试。与野生型相比,奇异变形杆菌pmfA/mrpA-D突变体对尿路上皮细胞的体外黏附能力降低,不过与单mrpA-D和pmfA突变体相比未观察到显著差异。然而,体内试验表明,与野生型和两个单突变体相比,奇异变形杆菌pmfA/mrpA-D突变体在肾脏和膀胱中的定殖显著减少。这些结果表明,尽管可能存在冗余,但MR/P和PMF菌毛在奇异变形杆菌UTI中具有特定且累加的作用。