Download E. coli 83972

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
%
Dementia incidence in Americans
65 Yrs
40대
50대
60대
70대
80대
90대
85 Yrs
40%
50%
Prevalence in BPH patients
60%
70%
80%
90%
Long-term catheterization
Urologic complications in 337 spinal cord injury patients
Complications
No. of Pts.
%
Acute pyelonephritis
Epididymitis
Bladder stone
33
15
16
9.7
4.4
4.7
VUR
Low vesical compliance
Autonomic dysreflexia
Other
14
14
13
30
4.1
4.1
4
8.9
18.8%
Korean J Urol 1997;38:1075-1080
Bacterial interferences
From wikipedia
From E-medicine
Biological interference in Nature
acacia
Beltian body
From Microbial Ecology by McArthur JV, Academic Press
Basic concepts for interference
Absence of pathogenicity island
Survival or growth advantage
E-coli 83972
From young girl in Sweden
OR:K5:HOriginally 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
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
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
Type 1 pili
Physical map of the fim gene cluster from E. coli MG1655
From INFECT IMMUN, 2006;74: 781–785
MG1655
83972
Structure of the fim locus in E. coli 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-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
Bacterial interference for prevention of UTI: Randomized,
double-blind trial
From Clinical Infectious Diseases 2005; 41:1531–4
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
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%)
1 cycle
106 CFU/ml, 2/day for 3 consecutive days
Several cycles for lost cases
From UROLOGY 2001;58: 339–344
Urgent issues in the future
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