Lactobacillus crispatus Limits Bladder Uropathogenic E. coli Infection by Triggering a Host Type I Interferon Response

Abstract

Many urinary tract infections (UTIs) are recurrent because uropathogens persist within the bladder epithelial cells (BECs) for extended periods between bouts of infection. Because persistent uropathogens are intracellular, they are often refractive to antibiotic treatment. The recent discovery of endogenous Lactobacillus spp. in the bladders of healthy humans raised the question of whether these endogenous bacteria directly or indirectly impact intracellular bacterial burden in the bladder. Here, we report that in contrast to healthy women, female patients experiencing recurrent UTIs have a bladder population of Lactobacilli that is markedly reduced. Exposing infected human BECs to L. crispatus in vitro markedly reduced the intracellular uropathogenic Escherichia coli (UPEC) load. The adherence of Lactobacilli to BECs was found to result in increased type I interferon (IFN) production, which in turn enhanced the expression of cathepsin D within lysosomes harboring UPECs. This lysosomal cathepsin D–mediated UPEC killing was diminished in germ-free mice and type I IFN receptor–deficient mice. Secreted metabolites of L. crispatus seemed to be responsible for the increased expression of type I IFN in human BECs. Intravesicular administration of Lactobacilli into UPEC-infected murine bladders markedly reduced their intracellular bacterial load suggesting that components of the endogenous microflora can have therapeutic effects against UTIs.

Use of probiotic lactobacilli in the treatment of vaginal infections: In vitro and in vivo investigations

“…Similarly, lactobacilli also have a protective effect against E. coli infection. By the induction of a host IFN-1 response, which in turn increases the production of cathepsin D within lysosomes to kill the pathogen, L. crispatus can alleviate bladder uropathogenic E. coli infection in a mouse model ( Song et al., 2022 ). In mice, serial vaginal inoculation with probiotic L. reuteri gives partial protection against S. agalactiae infections, and this effect is mediated in part by mucosal immunity ( Brokaw et al., 2021 ).…”

Reply by Authors

“…Lactobacillus may have utility as a probiotic for prevention of device biofilms, and as a therapeutic for urinary tract infection. 2,3 The findings call for investigation of the relationship among antibiotic exposure, dysbiosis of urinary tract and ureteral stent niches, and infection. They underscore the development of novel approaches to treat and prevent device-associated infection without selecting for antibiotic resistance.…”

“…Lactobacillus may have utility as a probiotic for prevention of device biofilms, and as a therapeutic for urinary tract infection. 2,3…”

The Urinary Microbiome: Role in Bladder Cancer and Treatment

“…Acid-producing Lactobacillus species can contribute to keeping pathogenic bacteria unable to survive in a more acidic environment at bay, and thus assume a protective role in the bladder [ 10 ]. Indeed, a recent study found that Lactobacillus in the bladder can protect the host from uropathogenic E. coli infection by triggering type I IFN production [ 31 ]. Price et al found that Lactobacillus in women showed no correlation with various factors such as age but discovered that other genera do differ among age groups; Gardnerella and Escherichia were more commonly found in younger and older women, respectively [ 32 ].…”