Reversible cell filamentation of uropathogenic Escherichia coli (UPEC) and the role of the cedA gene in urinary tract infections

Blair TA, Iosifidis G, Mediati DG and Duggin IG

Faculty of Science, University of Technology Sydney, PO Box 123, Broadway NSW 2007, Australia.

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 UPEC’s invasive lifecycle it undergoes remarkable morphological changes, including extensive cell filamentation—caused by a block to cell division with ongoing bacterial cell growth and elongation. It has been noted that the filamentation observed during UTI accompanies the rupture of the infected bladder cells. Re-initiation of division at multiple sites along the length of the filaments generates the short rod-shaped bacteria. The regulatory mechanisms that control filamentation and its reversal to allow for reinfection are unresolved. This project aims to test our hypothesis that the E. coli cedA gene (for cell division activator) is involved in regulating filamentation in UPEC. Previous work showed that overexpression of cedA prevents filamentation in a mutant strain of E. coli, called dnaA(cos), which conditionally over-replicates the chromosome and becomes filamentous. We found that dnaA(cos) filamentation is dependent on the RecA and SlmA DNA-binding proteins, consistent with a model in which the SlmA-DNA inhibits division under these conditions. Similarly, cedA was recently implicated in counteracting the effects of an antibiotic drug that blocks cell division. In UPEC, cedA was previously shown to be under positive selection, and was also found to be upregulated 8.4-fold during the filamentation stage of the UPEC infection cycle in cultured human bladder cells. We are currently determining the types of cell division blockage that can be prevented by cedA expression, and we are characterizing the phenotypic and transcriptional impact of cedA in vitro and in experimental models of UTI.