Menu

VCKD Members

Mnsl2p9r

Maria Hadjifrangiskou Ph.D.

Department: Pathology, Microbiology & Immunology

Biography

Urinary tract infections (UTIs) are among the most frequent bacterial infections, are highly prevalent among women and have a high degree of recurrence. Currently, antibiotics are the primary treatment option for UTI, however they oftentimes fail to eliminate infection, they perturb the host microbiota and select for increased antibiotic resistance. This means that there is a pressing need for the development of alternative strategies for preventing and/or treating UTIs. Uropathogenic Escherichia coli (UPEC), which causes 85% of all UTIs, has evolved a remarkable mechanism to evade host immune defenses and establish infection, by forming biofilm-like intracellular bacterial communities (IBC) inside bladder cells, in addition to forming extracellular biofilms on host cell surfaces and on catheter implants. My lab is interested in identifying factors and mechanisms that regulate UPEC biofilm formation and that could serve as new drug targets. We have performed a screen that has identified 41 such factors, including the QseBC signal transduction system, which we are currently characterizing in more detail. To do this, we use a wide variety of approaches, including molecular biology, cell-based and in vitro assays, chemical biology and 3 mouse models of UTI. Another  approach we are taking advantage of is imaging mass spectrometry, which has allowed us to discern differential protein profiles within surface-associated biofilms and uncovered complex regulatory cascades that lead to differential protein stratification in the biomass. Finally, another area of interest in the lab is to understand the mechanism by which rationally designed small molecules act against UPEC pathogenesis. These small molecular weight inhibitors were initially designed to block pilus assembly, thereby impeding bacterial adherence to biotic and abiotic surfaces; we have come to discover that these molecules impact UPEC gene expression, causing pleiotropic effects on virulence gene regulation and inhibiting biofilm formation. In collaboration with labs at Washington University in Saint Louis and Umea University in Sweden, we are working towards understanding how these inhibitors function and how they can be optimized for use as treatments against UTIs.

Featured Publications

See all publications

Publications