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Escherichia coli FimH adhesins act synergistically with PapGII adhesins for enhancing establishment and maintenance of kidney infection
Institution:1. Division of Nephrology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan;2. Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan;3. Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan;4. Institute of Molecular Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan;5. Department of Biotechnology and Laboratory Science in Medicine, School of Biomedical Science and Engineering, National Yang Ming University, Taipei, Taiwan
Abstract:BackgroundFimH adhesin is proposed to enhance Escherichia coli kidney infection by acting with PapGII adhesin, but genetic epidemiology study and animal study have not been widely conducted to confirm this hypothesis.MethodsWe compared the prevalence of adhesin gene and their coexistent pattern between upper and lower urinary tract infection (UTI) strains. fimH mutant (EC114FM), papGII mutant (EC114PM) and fimH/papGII double mutant (EC114DM) were constructed from a pylonephritogenic strain (EC114). We compared among these strains for the infection ability in bladders and kidneys of female BALB/c mice challenged transurethrally with these bacteria and assessed 1, 3, and 7 days after inoculation.ResultsStrains carrying fimH-only genotype were significantly more prevalent in lower UTI (P < 0.001). Strains carrying the fimH/papGII, but not papGII-only, were significantly associated with upper UTI (P = 0.001). Incidence of kidney infection increased after inoculation with EC114 on days 1 and 3, at both low and high dose, as compared with EC114DM; and the effect was greater than the sum of individual effect of EC114PM and EC114FM. Geometric means of quantitative bacterial counts in the kidneys significantly decreased when challenged with EC114FM on days 3 and 7, EC114PM on day 3 and EC114DM on day 1 after inoculation at high dose, as compared with EC114 (all P < 0.05).ConclusionsWe confirmed the advantage and synergistic action of FimH and PapGII for E. coli kidney infection and concluded that antagonists against FimH and PapGII adhesin may prevent kidney infection and enable its management.
Keywords:Adhesins  Urinary tract infection  Kidney infection
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