Recombinant antibodies against bacterial toxins: new tools for diagnosis and therapy urinary infections caused by uropathogenic Escherichia coli

Abstract

Urinary tract infection (UTI) is a disease with significant economic and social impact. Half of the women population will have at least one UTI episode during their life. The main cause of UTI is the uropathogenic Escherichia coli (UPEC). This is due to UPEC carry virulence factors such as alpha-hemolysin (HlyA) and cytotoxic necrotizing factor 1 (CNF1). These toxins can cause cell death, HlyA is a forming-pore toxin and CNF1 can alter the cytoskeleton structure. It is worth to mention that up to 60% of UPEC strains produce HlyA and circa of 40% express CNF1; these toxins can be considered excellent targets for diagnostic and therapeutic interventions. Diagnosis using molecular methods is expensive and requires trained personnel; antibiotics based-treatment generates acquisition of resistance. Thus, recombinant antibodies able to recognize and neutralize the toxins HlyA and CNF1 are a promising proposal for the diagnosis and treatment of UTI caused by UPEC, contributing to the reduction of social and economic burden of this disease. Therefore, we aim to obtain not only the heterologous proteins HlyA and CNF1 in a prokaryotic expression system, but also the synthetic antibodies through the phage display methodology. Thus, after obtention of these tools we will be able to offer an immunodiagnosis based-assay and, optimistically in the future, a novel human therapy for this pathology avoiding the indiscriminate uses of antibiotics. (AU)