The role of P fimbriae for Escherichia coli establishment and mucosal inflammation in the human urinary tract
Author
Summary, in English
Bacterial adhesion to the bladder mucosa is a critical step for the establishment of Escherichia coli bacteriuria. The P-fimbriae, encoded by the pap gene cluster, are considered as virulence factors but the mechanisms have been debated. This study defined the roles for P fimbriation during the early colonization of the human urinary tract.
Patients with recurrent UTI were first subjected to deliberate colonization with the non-fimbriated ABU strain E. coli 83972. Bacteriuria was established long term (1-4 years) in patients with dysfunctional bladders, but not in the patients with normal bladder function. Super-infections were transient and asymptomatic (Paper 1).
P fimbriae enhanced the establishment of bacteria in the human urinary tract. P fimbriated transformants of the ABU strain (E. coli 83972pap+/prs+) reached 105 CFU/ml more rapidly than E. coli 83972 and the vector control. This was demonstrated by group wise and intra-individual analysis, in patients colonized on different occasions with E. coli 83972 or the P fimbriated transformants (Paper 2).
P fimbriated E. coli triggered the host response more efficiently than the ABU strain. Higher neutrophil numbers and IL-8 and IL-6 concentrations in urine were obtained after colonization with the P fimbriated transformants. These results demonstrated that transformation of E. coli 83972 with the pap sequences is sufficient to convert it to a more potent host response inducer (Paper 3).
The P fimbriae were shown to lower the significant bacteriuria threshold. The P fimbriated transformants needed lower bacterial numbers (103-4 CFU/ml) to predict a positive second urine culture with a > 80% accuracy and to trigger a significant host response (Paper 4).
The expression of P fimbriae in vivo was monitored using a gfp reporter gene construct. Following inoculation, E. coli 83972pap+ gfp+ adhered to the uroepithelial cells. A host response was triggered, and the cells were cleared from adherent bacteria. In parallell, neutrophils containing GFP protein were detected. The results demonstrated that P fimbriae mediate adherence in the human urinary tract, and illustrate the complex interaction with the host response exemplified by neutrophils (Paper 5).
These studies show that P fimbriae fulfil the Koch Henles molecular postulates for bacterial establishment and host response induction in the human urinary tract.
Patients with recurrent UTI were first subjected to deliberate colonization with the non-fimbriated ABU strain E. coli 83972. Bacteriuria was established long term (1-4 years) in patients with dysfunctional bladders, but not in the patients with normal bladder function. Super-infections were transient and asymptomatic (Paper 1).
P fimbriae enhanced the establishment of bacteria in the human urinary tract. P fimbriated transformants of the ABU strain (E. coli 83972pap+/prs+) reached 105 CFU/ml more rapidly than E. coli 83972 and the vector control. This was demonstrated by group wise and intra-individual analysis, in patients colonized on different occasions with E. coli 83972 or the P fimbriated transformants (Paper 2).
P fimbriated E. coli triggered the host response more efficiently than the ABU strain. Higher neutrophil numbers and IL-8 and IL-6 concentrations in urine were obtained after colonization with the P fimbriated transformants. These results demonstrated that transformation of E. coli 83972 with the pap sequences is sufficient to convert it to a more potent host response inducer (Paper 3).
The P fimbriae were shown to lower the significant bacteriuria threshold. The P fimbriated transformants needed lower bacterial numbers (103-4 CFU/ml) to predict a positive second urine culture with a > 80% accuracy and to trigger a significant host response (Paper 4).
The expression of P fimbriae in vivo was monitored using a gfp reporter gene construct. Following inoculation, E. coli 83972pap+ gfp+ adhered to the uroepithelial cells. A host response was triggered, and the cells were cleared from adherent bacteria. In parallell, neutrophils containing GFP protein were detected. The results demonstrated that P fimbriae mediate adherence in the human urinary tract, and illustrate the complex interaction with the host response exemplified by neutrophils (Paper 5).
These studies show that P fimbriae fulfil the Koch Henles molecular postulates for bacterial establishment and host response induction in the human urinary tract.
Publishing year
2001
Language
English
Document type
Dissertation
Publisher
Department of Urology, Clinical Sciences, Lund University
Topic
- Microbiology in the medical area
- Immunology in the medical area
Keywords
- bacteriology
- Microbiology
- asymptomatic bacteriuria
- urinary tract infections
- deliberate colonization
- E. coli 83972
- P-fimbriae
- Mucosal host response
- IL-6
- IL-8
- neutrophils
- regulation.
- GFP
- virology
- mycology
- Mikrobiologi
- bakteriologi
- virologi
- mykologi
Status
Published
Supervisor
- [unknown] [unknown]
ISBN/ISSN/Other
- ISBN: 91-628-4696-5
Defence date
28 February 2001
Defence time
10:15
Defence place
Rune Grubbs Sal, Sölvegatan 23, 223 62 Lund
Opponent
- Walter Stamm (Professor)