Colicin E2 Expression in Lactobacillus brevis DT24, A Vaginal Probiotic Isolate, against Uropathogenic Escherichia coli

Novel therapeutic approaches are needed to combat the urinary tract infection in women. During menstruation elevated protein concentration and increase in oxygen and carbon dioxide concentrations with decrease in vaginal Lactobacilli all together contribute to urinary tract infections. Lactobacillus species are a predominant member of the vaginal microflora and are critical in the prevention of a number of urogenital diseases. In order to increase antimicrobial potential of vaginal Lactobacilli, bacteriocin colicin E2 which has specific activity against uropathogenic Escherichia coli has been overexpressed in vaginal probiotic Lactobacillus brevis DT24. Recombinant Lactobacillus brevis DT24 expressing colicin E2 showed much higher inhibitory activity against uropathogenic Escherichia coli than wild type L. brevis DT24 in vitro. Efficacy of probiotic Lactobacillus brevis DT24 expressing colicin E2 protein is required for further in vivo evaluation. 1. Introduction Urinary tract infection (UTI) is the most widespread infection in women worldwide after intestinal infection [1]. UTIs affect an estimated 1 out of 3 women before the age of 24 [2, 3]. Up to 40 to 50% of the female population will develop a symptomatic UTI at some time during their lives [2, 3] or develop complicated UTIs [4]. Recurrent UTI (rUTI) is a common syndrome in young healthy women. Previous studies suggest that 27% to 44% of women, who experienced an initial UTI, develop rUTI [5, 6]. UTI has the potential for severe and life-threatening sequelae if left untreated or undertreated. Possible sequelae include pyelonephritis which can lead to renal scarring and sepsis [7]. UTI can be particularly dangerous in pregnant women in whom it has been shown that up to 50% of those with asymptomatic bacteriuria (ABU) leads to develop pyelonephritis. In addition, these women experience higher rates of intrauterine growth restriction and low birth weight infants. The presence of a UTI has also been shown to increase the risk of preterm labor, preterm birth, pregnancy-induced hypertension, preeclampsia, amnionitis, and anemia [8]. Escherichia coli are among the most significant human pathogens, responsible for up to 90% of all community acquired and almost 50% of nosocomial UTIs. E. coli is a ubiquitous human pathogen responsible for both community and hospital-acquired infections [9, 10]. A number of virulence determinants facilitate the ability of uropathogenic E. coli to colonize the urinary tract and exert cytopathic effects, including type 1 fimbriae [11], P fimbriae [12], Dr adhesions [13],