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

• Grant number: 16/16188-7
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: March 01, 2018
• End date: November 16, 2020
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Roxane Maria Fontes Piazza
• Grantee: Bruna de Lucca Caetano
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated scholarship(s): 19/23686-1 - Production of HlyA and CNF1 bacterial toxins and biopanning of recombinant antibodies, BE.EP.DR

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)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

PRUDENCIO, CARLOS ROBERTO; DA COSTA, VIVALDO GOMES; ROCHA, LETICIA BARBOZA; DA COSTA, HERNAN HERMES MONTEIRO; ORTS, DIEGO JOSE BELATO; SANTOS, FELIPE ROCHA DA SILVA; RAHAL, PAULA; LINO, NIKOLAS ALEXANDER BORSATO; DA CONCEICAO, PAMELA JOYCE PREVIDELLI; BITTAR, CINTIA; et al. Identification of Zika Virus NS1-Derived Peptides with Potential Applications in Serological Tests. Viruses-Basel, v. 15, n. 3, p. 20-pg., 2023-03-01. (16/20045-7, 16/16188-7, 17/50333-7, 16/23560-0, 15/17178-2, 16/05570-8, 17/24769-2)