Urinary Tract Infections (UTIs) are one of the most common and significant bacterial infections worldwide. Unfortunately with the rise of antibiotic resistance by most bacteria, the treatment for UTIs is becoming less effective and research into new methods of treatment as well as prevention are necessary.
During UPECs invasive lifecycle it undergoes morphological changes, including filamentation. Filamentation is the result of ceased cell division during ongoing bacterial cell growth and chromosome replication. It has been noted that the filamentation of UPEC accompanies the rupture of the infected bladder cells. The bacterial filaments are then able to reinitiate division along the length of the filaments and revert to common rod-shaped cells. The regulatory mechanism that enables the filaments to revert to rod-shaped bacteria to allow for reinfection is unknown.
This project aims to test our hypothesis that the cedA gene contributes to the reinitiation of cell division during the filament reversal of UPEC. cedA has previously been implicated in the prevention of filamentation induced in a mutant strain of E. coli K-12 (called dnaA(cos)) that over-replicates the chromosome and becomes filamentous when the mutation is activated. cedA has also been shown to be under positive selection in UPEC strains. Thirdly, cedA was found to be upregulated 8.4-fold during the filamentation stage of the UPEC infection cycle in cultured human bladder cells. To better understand the function of this intriguing gene, we are determining whether cedA overexpression can prevent or reverse several of the known pathways that induce filamentation, including experimental UTI. We are also determining phenotypic and transcriptional consequences of deletion of cedA in both UTI89 (uropathogenic) and K-12 (commensal) E. coli. Our data so far suggest that cedA overexpression can prevent filamentation that is caused via the SOS (DNA damage) response but it cannot reverse pre-formed filaments.