Urinary tract infections (UTIs) caused by uropathogenic Escherichia coli (UPEC) are one of the most common and recurrent infections worldwide. More than 50% of women will suffer at least one UTI in their lifetime and despite effective antibiotic treatment, over 50% of patients will experience at least one recurrence within a year. These findings suggest that current treatment regimens are not ideal. So far, most strategies to combat infectious diseases have been designed to act against the pathogen. As the host response is integral in determining the infection outcome, manipulation of the host represents an innovative strategy to fight UTIs. To develop such therapeutic strategies, our research group aims to better understand urinary tract infections from the host perspective, deciphering the role and impact that specific host factors and/or pathways have on the outcome of the infection.

    We use adult stem cell derived-organoids and organoid-based models to closely mimic the natural infection site and combine them with miRNome profiling, single-cell RNA-sequencing (scRNA-seq), and gain- and loss-of-function assays to identify and functionally characterize specific host factors and/or pathways controlling UPEC infection.

     Advanced organoid-based models

    The vast majority of UTIs occur in the bladder. To closely mimic the in-vivo infection setting of urinary tract infections, we use adult stem cell-derived bladder organoids. These organoids are generated from adult stem cells present in the bladder epithelium and can be used as a source of expandable primary cells to establish other in-vitro models, such as 2D monolayers or more advanced tissue engineering models. Because these cells can differentiate and self-organize as in the organ in vivo, they represent a very powerful tool for infection biology.

    Role of microRNA in bacterial infection 

    As major post-transcriptional regulators, microRNAs (miRNAs) have emerged as crucial players in the fight against invading pathogens. MiRNAs can regulate the outcome of an infection by modulating eventually any host function, including the immune response, cell cycle, cell death, and autophagy. We study how miRNAs are regulated in the human bladder epithelium upon bacterial infection and how we could use specific miRNAs to control the infection.

    Host pathways controlling bacterial infection

    Bacterial pathogenesis and the ensuing host response are highly complex and heterogeneous processes. For example, while the UPEC replicates in some urothelial cells, it stays dormant in others. Understanding the host factors/pathways involved in this different behaviour could lead to the discovery of new targets to develop new therapeutics. We use scRNA-seq to study the host requirements of UPEC to replicate or persist in urothelial cells at the single-cell level.