Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Australia.
J Infect Dis. 2012 Oct;206(8):1242-9. doi: 10.1093/infdis/jis493. Epub 2012 Aug 7.
Urinary tract infections (UTIs) caused by uropathogenic Escherichia coli (UPEC) are a significant health concern, exacerbated by the rapid emergence of multidrug resistant strains refractory to antibiotic treatment. P fimbriae are strongly associated with upper urinary tract colonization due to specific binding to α-D-galactopyranosyl-(1-4)-β-D-galactopyranoside receptors in the kidneys. Thus, inhibiting P-fimbrial adhesion may reduce the incidence of UPEC-mediated UTI. E. coli 83972 is an asymptomatic bacteriuria isolate successfully used as a prophylactic agent to prevent UTI in human studies. We constructed a recombinant E. coli 83972 strain displaying a surface-located oligosaccharide P fimbriae receptor mimic that bound to P-fimbriated E. coli producing any of the 3 PapG adhesin variants. The recombinant strain, E. coli 83972::lgtCE, impaired P fimbriae-mediated adhesion to human erythrocytes and kidney epithelial cells. Additionally, E. coli 83972::lgtCE impaired urine colonization by UPEC in a mouse UTI model, demonstrating its potential as a prophylactic agent to prevent UTI.
尿路致病性大肠杆菌(UPEC)引起的尿路感染(UTI)是一个严重的健康问题,由于对抗生素治疗产生抗药性的多药耐药菌株的迅速出现,情况更加恶化。P 菌毛与肾脏中的α-D-半乳糖基-(1-4)-β-D-半乳糖苷受体特异性结合,因此与上尿路感染的定植密切相关。因此,抑制 P-菌毛的黏附可能会降低 UPEC 介导的 UTI 的发生率。大肠杆菌 83972 是一种无症状菌尿分离株,已成功用作预防人类 UTI 的预防性药物。我们构建了一种重组大肠杆菌 83972 菌株,该菌株表面展示了一种寡糖 P 菌毛受体模拟物,可与产生任何 3 种 PapG 黏附素变体的 P 菌毛化大肠杆菌结合。重组菌株大肠杆菌 83972::lgtCE 削弱了 P 菌毛介导的对人红细胞和肾上皮细胞的黏附。此外,大肠杆菌 83972::lgtCE 在小鼠 UTI 模型中削弱了 UPEC 的尿液定植,表明其具有作为预防 UTI 的预防性药物的潜力。