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

• Grant number: 17/25406-0
• Support Opportunities: Regular Research Grants
• Start date: June 01, 2018
• End date: May 31, 2020
• Field of knowledge: Health Sciences - Collective Health - Public Health
• Principal Investigator: Roxane Maria Fontes Piazza
• Grantee: Roxane Maria Fontes Piazza
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated researchers: Daniela Luz Hessel da Cunha
• Associated research grant(s): 18/13895-0 - Phage library for generation of recombinant antibodies: novel approaches for diagnosis and therapy of infections caused by different Escherichia coli pathotypes, AP.R SPRINT

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)

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)

MUNHOZ, DANIELLE D.; SANTOS, FERNANDA F.; MITSUNARI, THAIS; SCHUROFF, PAULO A.; ELIAS, WALDIR P.; CARVALHO, ENEAS; PIAZZA, ROXANE M. F.. Hybrid Atypical Enteropathogenic and Extraintestinal Escherichia coli (aEPEC/ExPEC) BA1250 Strain: A Draft Genome. PATHOGENS, v. 10, n. 4, APR 2021. (18/06610-9, 17/25406-0, 17/14821-7)