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Bacterial interference for preventing UTI

Bacterial interference for preventing UTI. Gilho Lee, MD Department of Urology Dankook University Medical School. Life expectancy in Korea. Ages. Women Men. 1960 1971 1975 1981 1985 1989 1995 2002 Years. From http://nsportal.stat.go.kr. 40%. 40 대

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Bacterial interference for preventing UTI

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  1. Bacterial interference for preventing UTI Gilho Lee, MD Department of Urology Dankook University Medical School

  2. Life expectancy in Korea Ages Women Men 1960 1971 1975 1981 1985 1989 1995 2002 Years From http://nsportal.stat.go.kr

  3. 40% 40대 50대 60대 70대 80대 90대 50% 60% 70% 80% 90% % Dementia incidence in Americans 65 Yrs 85 Yrs Prevalence in BPH patients

  4. Long-term catheterization

  5. Urologic complications in 337 spinal cord injury patients Complications No. of Pts. % Acute pyelonephritis 33 9.7 Epididymitis 15 4.4 Bladder stone 16 4.7 VUR 14 4.1 Low vesical compliance 14 4.1 Autonomic dysreflexia 13 4 Other 30 8.9 18.8% Korean J Urol 1997;38:1075-1080

  6. Bacterial interferences From wikipedia From E-medicine

  7. Biological interference in Nature acacia Beltian body From Microbial Ecology by McArthur JV, Academic Press

  8. Basic concepts for interference

  9. Absence of pathogenicity island Survival or growth advantage

  10. From young girl in Sweden OR:K5:H- Originally from ECOR B2 Pathogenicity island p-fimbriae type 1 fimbriae E-coli 83972

  11. P-fimbriae PN associated pili -Pathogenic island Pap A, H, K, E, F, G Mannose resistance pili Glycosphingolipid binding Type 1 fimbriae Pathogenic island ? Fim A, I, F, G, H Bind to uroplakin Ia, Ib Mannose sensitive pili Glycoprotein binding

  12. Intra-cellular pathways MAPK: Mitogen-Activated Protein Kinase MEK: MARK kinase NIK: NF-κB-inducing kinase MEKK1: MAPK/ERK kinase kinase-1 IKK: IκB kinase Surh YJ, Chun KS, Cha HH, et al. Mutation Research 480–481 (2001) 243–268

  13. Pap protein in E-coli 83972 From INFECT IMMUN, 2006;74: 781–785

  14. Physical map of the pap gene cluster from E. coli 83972 and the amino acid identity of each of the predicted proteins with the respective protein from E. coli CFT073

  15. E-coli 83972 E-coli 83972+all pap (s papG) E-coli 83972+only papG A: RBC, B: Uro-epithelium From INFECT IMMUN, 2006;74: 781–785

  16. Type 1 pili Physical map of the fim gene cluster from E. coli MG1655 From INFECT IMMUN, 2006;74: 781–785

  17. MG1655 83972 Structure of the fim locus in E. coli 83972 From INFECT IMMUN, 2006;74: 781–785

  18. Growth of ABU E. coli 83972 and UPEC strains 536, CFT073, NU14, and 1177 in human urine • The doubling time during exponential phase for each strain • Competition experiment between 83972 and NU14 mixed 1:1 at the starting point in human urine From INFECT IMMUN. 2006;74: 615–624

  19. Growth competition experiments (1:1) between E. coli 83972 and UPEC strains after 17 h of growth in human urine 83972: Non-UPEC 536: UPEC (O6:K15:H31) CFT073: UPEC (O6:K2:H1) NU14: UPEC (O18:K1:H7) 1177: UPEC (O1:K1:H7) From INFECT IMMUN. 2006;74: 615–624

  20. Bacterial interference for prevention of UTI: Randomized, double-blind trial From Clinical Infectious Diseases 2005; 41:1531–4

  21. E-coli 83972 inhibits catheter adherence by a broad spectrum of uropathogens P=0.03 p=0.03 p=0.02 From UROLOGY 2003;61: 1059–1062

  22. No. Colonized with 83972/No. Inoculated (%) 1mo 3mo 6mo 12mo Patients30/44 (68%) 21/44 (48%) 13/43 (30%) 9/41 (22%) Likelihood of bladder colonization with E-coli 83972 1 cycle 106 CFU/ml, 2/day for 3 consecutive days Several cycles for lost cases From UROLOGY 2001;58: 339–344

  23. Urgent issues in the future • Need multiple groups, possibly partnering with a commercial interest to speed up the process. • 2. No invasion of the host and not causing an inflammatory host response. • Does it stay in the bladder, or does it also migrate into the upper tracts, especially obstructed urinary tract or the immunocompromised host? • 3. Undesirable effects: odors, antibiotics resistance gene transfer. From Ronald AR, Clinical Infectious Diseases 2005; 41:1535–6

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