Bacterial interference for preventing UTI

Gilho Lee, MD

Department of Urology

Dankook University Medical School

Life expectancy in Korea

Ages

1960 1971 1975 1981 1985 1989 1995 2002 Years

From http://nsportal.stat.go.kr

Women Men

% Dementia incidence in Americans

65 Yrs 85 Yrs

40대

50대

60대

70대

80대

90대

40%

50%

60%

70%

80%

90%

Prevalence in BPH patients

Long-term catheterization

Urologic complications in 337 spinal cord injury patients

Complications No. of Pts. %

Acute pyelonephritis 33 9.7 Epididymitis 15 4.4Bladder stone 16 4.7

VUR 14 4.1Low vesical compliance 14 4.1Autonomic dysreflexia 13 4Other 30 8.9

Korean J Urol 1997;38:1075-1080

18.8%

Bacterial interferences

From wikipedia From E-medicine

Beltian body

acacia

From Microbial Ecology by McArthur JV, Academic Press

Biological interference in Nature

Basic concepts for interference

Absence of pathogenicity island Survival or growth advantage

E-coli 83972

From young girl in Sweden

OR:K5:H-

Originally from ECOR B2

Pathogenicity island

p-fimbriae

type 1 fimbriae

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

Surh YJ, Chun KS, Cha HH, et al. Mutation Research 480–481 (2001) 243–268

MAPK: Mitogen-Activated Protein KinaseMEK: MARK kinase

NIK: NF-κB-inducing kinase MEKK1: MAPK/ERK kinase kinase-1IKK: IκB kinase

Intra-cellular pathways

Pap protein in E-coli 83972

From INFECT IMMUN, 2006;74: 781–785

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

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

Physical map of the fim gene cluster from E. coli MG1655

Type 1 pili

From INFECT IMMUN, 2006;74: 781–785

Structure of the fim locus in E. coli 83972

MG1655

83972

From INFECT IMMUN, 2006;74: 781–785

(A) Growth of ABU E. coli 83972 and UPEC strains 536, CFT073, NU14, and 1177 in human urine (B) The doubling time during exponential phase for each strain (C) Competition experiment between 83972 and NU14 mixed 1:1 at the starting point in human urine

From INFECT IMMUN. 2006;74: 615–624

Growth competition experiments (1:1) between E. coli 83972 and UPEC strains after 17 h of growth in human urine

83972: Non-UPEC536: 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

Bacterial interference for prevention of UTI: Randomized, double-blind trial

From Clinical Infectious Diseases 2005; 41:1531–4

P=0.03 p=0.03 p=0.02

E-coli 83972 inhibits catheter adherence by a broad spectrum of uropathogens

From UROLOGY 2003;61: 1059–1062

From UROLOGY 2001;58: 339–344

Likelihood of bladder colonization with E-coli 83972

No. Colonized with 83972/No. Inoculated (%) 1mo 3mo 6mo 12mo

Patients 30/44 (68%) 21/44 (48%) 13/43 (30%) 9/41 (22%)

106 CFU/ml, 2/day for 3 consecutive daysSeveral cycles for lost cases

1 cycle

1. 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

Urgent issues in the future