'A 3D Infection Model to Determine How d-Mannose Could Reduce Recurrent Urinary Tract Infections' by Sakina Ahmed
Urinary tract infections (UTI) are the second most common type of bacterial infection worldwide. They are often recurrent, annually affecting millions of people, mainly women. The increasing challenge of antibiotic resistance is severely threatening the success of current treatments and there is an urgent need for alternative strategies to reduce this disease burden. Uropathogenic Escherichia coli (UPEC) are the primary cause of UTI and cause disease by binding to and invading the lining of the bladder. We are using a 3D infection model to investigate UPEC binding in the presence of urine collected from women enrolled on a clinical trial of d-mannose, which has been proposed to reduce E. coli binding. We compared the growth of three types of UPEC in artificial urine. All grew more slowly in urine than in nutrient-rich bacterial growth medium. However, strains CFT073 and 536 were better adapted to this environment than UTI89. Next, we grew specialised cells from the lining of the human bladder and differentiated them on porous membranes to establish a 3D model of a bladder lining. We then used a gentamycin protection assay to show that CFT073 can bind to the differentiated bladder cells and that both can withstand exposure to urine for 24 hours. The initial results suggest that CFT073 binding was reduced in the presence of urine in sample 7 and 9, compared to the control groups. Our data will provide a mechanistic understanding of how prophylactic d-mannose may prevent recurrent UTI and reduce the global burden of disease.