Recombinant antibodies against alpha-hemolysin and CNF1 toxins for the diagnosis and therapy of uropathogenic Escherichia coli

Abstract

Urinary Tract Infection (UTI) is a disease with significant economic and social impact. Half of the woman population will have at least one UTI episode during their life. The main cause of UTI is 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 capable of forming pores in the host membrane and CNF1 can alter the cytoskeleton structure. Keeping in mind that up to 60% of UPEC strains produce HlyA and about 40% express CNF1, these toxins become good targets for diagnostic and therapeutic interventions. However, diagnosis by molecular methods is expensive and requires trained personnel for its realization, and 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 thought the phage display methodology. And so on utilizing these tools to propose an immunodiagnosis assay and, hopefully in the future, a novel human therapy for this pathology. (AU)