A live-attenuated vaccine for the treatment of urinary tract infection by uropathogenic Escherichia coli

Abstract

Uropathogenic Escherichia coli are the leading cause of urinary tract infection. We recently demonstrated that deletion of the O antigen ligase gene, waaL, from the uropathogenic E. coliisolate NU14 results in a strain that stimulates enhanced urothelial cytokine secretion. Because enhanced innate immune responses are of interest in vaccine development, we examined the therapeutic potential of NU14 DeltawaaL as a vaccine for urinary tract infection. NU14 DeltawaaL stimulated enhanced interleukin-6 secretion by mouse macrophages, compared with secretion by the wild type. Mice vaccinated via instillation into the bladder developed protective responses that prevented persistent colonization after bladder challenge with NU14, yet NU14 DeltawaaL failed to persistently colonize the mouse bladder. Inoculation with the vaccine strain protected mice against challenge with a broad range of clinical uropathogenic E. coli isolates and produced immunity that lasted 8 weeks. Therefore, NU14 DeltawaaL is a candidate live-attenuated vaccine for the treatment and prevention of acute and recurrent urinary tract infection by caused by uropathogenic E. coli.