Prevention of urinary tract infection in rats with an indigenous Lactobacillus casei strain

Abstract

Our previous studies have shown that indigenous bacteria are able to block the in vitro attachment of uropathogenic bacteria to human uroepithelial cells. In the present study, we applied the concept of competitive exclusion to an animal model. A chronic urinary tract infection was established in female rats with bacteria incorporated into agar beads injected periurethrally into the urinary bladder via a no. 3 French ureteral catheter. Five strains of uropathogenic organisms were used in the first set of experiments, and their colonization of the bladder and kidneys of the animals was confirmed up to 2 months after injection. The uropathogens stimulated an immune response, detected by serum antibodies against the uropathogens, and an inflammatory response noted in sections of the kidneys stained with hematoxylin and eosin. Using this animal model, we established the persistent adherence of bacteria in the urinary tract without the need for creation of obstruction or implantation of a foreign body. In a second set of experiments, an isolate of Lactobacillus casei GR1 taken from the urethra of a healthy woman was incorporated into agar beads, instilled within the rat bladders on day 1, and then swabbed twice weekly for 21 days onto the introitus before challenge with uropathogens instilled into the urinary bladder. In 21 of 25 animals, no uropathogenic bacteria were recovered from the bladder and kidney tissues up to 60 days after challenge, and no immune response was detected. Our results show that L. casei prevented onset of urinary tract infection in 84% of the animals tested. The lactobacilli appeared to exclude the uropathogens from colonizing the urinary tract, within the first 48 hours after challenge, and the net effect was a complete eradication of bacteria from the uroepithelium. It is hoped that the demonstration of a protective role for indigenous bacteria in preventing urinary tract infection in an animal model will lead to the application of this technology to prevent recurrent urinary tract infection in female patients.