Ana Lidia Flores-Mireles
Assistant Professor, Department of Biological Sciences
University of Notre Dame
Dr. Flores-Mireles was appointed to the faculty of University of Notre Dame in 2018 as the Hawk Family Assistant Professor of the Department of Biological Sciences.
During her Postdoctoral training with Dr. Scott Hultgren and Dr. Michael Caparon at Washington University School of Medicine, she developed an interest in infectious diseases in the urinary tract. Her work understanding Enterococcus faecalis catheter-associated urinary tract infection (CAUTI) led her to discover that urinary catheterization in both mice and humans elicits bladder inflammation, resulting in the release of fibrinogen (Fg) into the bladder lumen which then becomes deposited onto the catheter. They found that the released Fg is critical for E. faecalis pathogenesis since Fg is used as a nutrient and exploits the Fg-coated catheters to form biofilms.
They unveiled that E. faecalis expresses a Fg-binding adhesin, EbpA, that tips the Ebp pilus, which binds directly to Fg via its N-terminal domain (EbpANTD) and this interaction is critical for the formation of catheter-associated biofilms. They were able to translate this work by showing that Enterococcus strains require Fg for catheter colonization in humans and that vaccination with EbpANTD protects against CAUTI. They also showed that passive immunization with anti-EbpANTD antibodies is effective both as a prophylactic and as a therapy for the reduction of bacterial titers. This therapy was also protective against a broad range of urinary tract, bloodstream, and GIT enterococcal clinical strains, which included E. faecalis, E. faecium, and VRE.
Importantly, they found that E. faecalis is not the only uropathogen that exploits fibrinogen such as S. aureus, E. coli, A. baumanni, C. albicans among others. Furthermore, inflammation not only contributes to infection but it has been shown that prolonged inflammation due to long-term catheterization is linked to proliferative pathological conditions. As an independent investigator, her laboratory research goals are to understand in detail how urinary catheterization-induced inflammation renders the host susceptible to microbial infection of the urinary tract and subsequent dissemination, as well as to understand the relationship between catheterization and inflammation-induced bladder cancer and whether infection plays a role in it. Understanding the role of inflammation on the development of CAUTI and cancer development will allow them to inform future catheterization guidelines focusing on reducing inflammation, providing a quality of life to those patients that require long-term urinary catheterization at the same time that it minimizes the risk for cancer development.