The antimicrobial activity of the intraurethrally administered probiotic Lactobacillus casei strain Shirota against Escherichia coli in a murine urinary tract infection (UTI) model was examined. UTI was induced by intraurethral administration of Escherichia coli strain HU-1 (a clinical isolate from a UTI patient, positive for type 1 and P fimbriae), at a dose of 1 ؋ 10 6 to 2 ؋ 10 6 CFU in 20 l of saline, into a C3H/HeN mouse bladder which had been traumatized with 0.1 N HCl followed immediately by neutralization with 0.1 N NaOH 24 h before the challenge infection. Chronic infection with the pathogen at 10 6 CFU in the urinary tract (bladder and kidneys) was maintained for more than 3 weeks after the challenge, and the number of polymorphonuclear leukocytes and myeloperoxidase activity in the urine were markedly elevated during the infection period. Urinary tract infection (UTI) is the most common bacterial infection seen in clinical practice. Human UTI comprises disease entities such as acute pyelonephritis with renal parenchymal involvement, cystitis limited to the urinary bladder, and asymptomatic bacteruria. Enterobacteriaceae such as Escherichia coli, which are normal inhabitants of human intestines, account for the vast majority of these uncomplicated infections (37,65). Appropriate hygiene and cleanliness of the genital area are therefore recommended for prevention of UTI. On the other hand, studies have shown a correlation between a loss or disruption of the normal genital microflora, in particular Lactobacillus species, and an increased incidence of genital and bladder infections (57). Preclinical and clinical reports have focused on lactobacillus strains, their possible prophylactic effects against experimental E. coli infection, and the use of these strains for the prevention of human urogenital infections (7,12,17,59,60).Suitable animal experimental models are required for appropriate preclinical studies of UTIs. Hagberg et al. were the first to show that mice could be challenged intravesically (by introducing pathogens directly into the bladder) without further manipulations of the urinary tract (18), and the murine model of ascending pyelonephritis has served as an excellent tool for defining the roles of individual virulence factors in the pathogenesis of UTI (18,23,25,26,28,61). It should be noted, however, that the inoculum doses used in murine models are very high (10 8 CFU). Furthermore, high bladder infection levels reportedly persisted over the 14-day study period only in C3H/HeJ and C3H/OuJ mice, which are lipopolysaccharide (LPS) nonresponder strains, while strains such as C3H/HeN, C57BL/6, BALB/c, DBA.1, DBA.2, and AKR showed progressive resolution of bladder infections over a 14-day period (23,24). Therefore, an appropriate model in which chronic UTI can be induced with a lower inoculum of E. coli, regardless of differences in genetic backgrounds, is needed.In the present report, we first describe an improved murine chronic infection model of UTI, in which the infection was induced by tr...