Uropathogenic Escherichia coli (UPEC strains) are the major causative agents of human urinary tract infections. UPEC employ several strategies to adhere, colonize and persist within the bladder niche. Understanding at a molecular level these strategies is surely a very important task in order to control these relevant pathogens, to limit bacterial transmission and to improve antibacterial strategies.
Here, by using an in vitro model of cultured bladder epithelial cells persistently infected with the E. coli strain EC73, a clinical isolate recently isolated from a patient presenting recurrent urogenital tract infections, we will analyze the mechanisms through which intracellular bacteria can trigger pathogen-specific bacterial persistence and damages of host cells. Our aim is to elucidate the mechanism(s) through which the interplay between bacterial and host factors led to specific pathogen alterations of epithelial cells.
Urinary tract infections (UTIs) are the most common diseases encountered in clinical practice worldwide and account for morbidity and high medical costs. E. coli is the predominant pathogen causing 80 to 90% of community-acquired UTIs and more than 30% of hospital-acquired UTIs. Recurrent UTIs (RUTIs) are reported in 16¿25% of women within six months and in 40¿50% within one year from a UTI episode, and thus pose a major clinical problem. Up to 77% of RUTIs are caused by E. coli strains identical to the primary infecting organism. The bacterial properties accounting for persistence or relapse of UTI have not been definitively characterized. In an effort to design effective therapeutics for counteracting UTIs and preventing RUTIs, we need a deeper understanding of how UPEC cope with host-associated factors and about the mechanisms of bacterial persistence within the susceptible hosts.
Namely, UTIs are generally accompanied by a robust innate inflammatory response involving neutrophil recruitment, that resolves the acute phase of bacterial infection. However, a remarkable persistence of E. coli within the bladder, a hallmark of UTI infection, was observed. The use of host innate immune defenses and the ability to modulate autophagy to increase bacterial adherence or invasion illustrates the complexity of host-pathogen interactions that may take place during UTI.
Over the past decade, several studies have shown that UPEC, long considered an extracellular pathogen, can invade epithelial cells of the urinary tract in both in vitro and in vivo. Host cell invasion provides survival advantage within the urinary tract so that it contributes significantly to the pathogenesis of UTIs. The invasive nature of these infections may explain, at least in part, the frequent recurrence of UTIs. The issue is made more relevant by the problems linked to antibiotic intracellular activity to and antibiotic resistance at large.
Recently, using the non-tumorigenic prostate epithelial cell line RWPE-1, we studied pathogen-host cell interactions and adaptive responses at the molecular and cellular level. The E. coli strain EC73, is able to adhere to, invade, to survive and persist within prostate epithelial cells, inducing a basal level of MAPK-kinase phosphorylation and synthesis and release of low amounts of IL-6 and IL-8.
Our data may add useful clues for a better understanding of the UPEC pathway able to promote growth and persistence in the hostile niche of the urinary tract; this would argue for new approaches to diagnosis and treatment of acute and chronic UTIs.