Urinary Tract InfectionUPEC genomics/geneticsChaperone/Usher Pathway PiliEnterococcal pathogenesis/catheter-associated UTIBacterial amyloid (Curli) biogenesisBacterial Community Interactions (Biofilms and Microbiome)Drug and Vaccine Development

Bacterial Community Interactions (Biofilms and Microbiome)

IBC in mouse bladder

IBC in mouse bladder

UPEC, like all bacteria exist in the host as part of a consortium of bacteria, which interact within clonal as well as mixed species communities. UPEC is able to form clonal biofilm-like intracellular bacterial communities (IBCs) within bladder epithelial cells, as well as on catheter material within the bladder.

Fibrous bacterial baskets in pellicles

Fibrous bacterial baskets in pellicles

In addition, UPEC can thrive within the host on periurethral surfaces and within the gastrointestinal tract sites as part of a diverse bacterial microbiota. In order to understand UPEC’s ability to survive and replicate within these environments, we have developed a number of in vitro monoculture biofilm models and we have studied factors that allow UPEC to colonize the gut in combination with differing gut bacterial communities. Biofilms consist of communities of bacteria within an extracellular matrix. Bacteria within these communities are more recalcitrant to antimicrobials and to host defense mechanisms and thus are a complicating factor in treatment of diseases in which biofilms are formed.

biofilms under different conditions

Biofilms under different conditions

Biofilm formation is sensitive to environmental conditions and UPEC biofilms produced intracellularly (IBCs) and on abiotic surfaces, such as catheters, are both relevant to UTI. We use a variety of biofilm models to study the differences and commonalities between UPEC biofilms. Our work focuses on trying to understand the role of CUP pili and other fibers in biofilm formation. We discovered that UPEC cystitis isolate UTI89 forms different types of biofilms in vitro depending on the environment: i) Curli-dependent biofilms that formed when UTI89 was grown in yeast extract-casamino Acids (YESCA) broth and ii) type 1 pili-dependent biofilms that formed when UTI89 was grown in LB broth. Using these conditions, a transposon library was screened to identify biofilm defective mutants that affected either curli or type 1 pili dependent biofilm formation or both. Further, some mutations that were defective in in vitro biofilms were subsequently shown to be defective in in vivo biofilms. In addition, as we have demonstrated for in vivo biofilm-like communities, diverse UPEC strains also show different abilities to form in vitro biofilms. Thus, we are investigating the regulatory networks underlying the formation, development, and maintenance of diverse UPEC biofilms in vitro. This work is giving insight into the range of genetic programs used by UPEC to initiate, organize and form a UPEC biofilm community. In addition, it is important to understand the impact that other bacterial species have on UPEC’s ability to form biofilms, reside within the gut microbiota and on periurethral surfaces. Finally, we are interested in elucidating how changes in the composition of the gut microbiota impact susceptibility to UTI.

Collaborators: John Heuser, Maria Hadjifrangiskou, Amanda Lewis, Jeff Gordon, Jeff Henderson.