Jeffrey Henderson, M.D., Ph.D.
The impact of siderophore-mediated iron acquisition by E. coli on urinary tract infection in young women
Abstract
Urinary tract infections (UTI) are a significant cause of morbidity worldwide and disproportionately affect young women. E. coli is the predominant cause of uncomplicated UTI and studies of clinical isolates have suggested that the ability to cause UTI correlates with acquisition of genes for uptake of siderophores – a chemically diverse family of small molecules that as functions iron scavengers. If true, therapeutic modulation of siderophore systems of the innate host defenses directed against them may be viable therapeutic or prophylactic strategies. I propose to test the hypothesis that competition for iron between siderophore systems and host defenses plays a critical role in urinary tract infection pathogenesis and recurrence. The proposed research will use a combined bacterial genetic and metabolomic approach in conjunction with in vitro, mouse cystitis, and patient-oriented studies directed toward themes of pathogen virulence and persistence.
Specific Aims
- To determine which siderophore systems are selected among UTI-associated strains and how these systems impact virulence-associated functions
- To identify the innate defenses driving selection of virulence-associated siderophore systems
