Development of DNA aptamers against uropathogens isolated in basic Health Care Units

• Grant number: 23/09791-2
• Support Opportunities: Scholarships in Brazil - Support Program for Fixating Young Doctors
• Start date: August 01, 2023
• End date: June 30, 2025
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Agreement: CNPq
• Principal Investigator: Silvia Figueiredo Costa
• Grantee: Marina Farrel Côrtes
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 23/02920-1 - Development of DNA aptamers against uropathogens isolated in basic Health Care Units, AP.R

Abstract

Infections caused by multidrug-resistant bacteria are a worldwide health problem and one of the main causes of human diseases with high mortality rates. Urinary tract infections (UTIs) are among the most common types of infectious diseases, with approximately 150 million cases per year worldwide, associated with high morbidity and health care costs. Rapid identification of these infections is critical, as they can be difficult to treat, with better prognostic chances when specific therapy is started early. In this context, the development of fast and economically viable detection methodologies, as well as the development of new therapeutic alternatives are urgent needs. The development of aptamers for specific recognition of infectious agents could be a solution. In addition to identification, the binding of the aptamer with its bacterial target can also block its function acting as a therapeutic tool. However, aptamer technologies for bacteria still have many setbacks, including the difficulty of the selection process. Escherichia coli and Klebsiella pneumoniae are among the pathogens most frequently isolated in cases of UTI. The objective of this work is to select and identify aptamers for the main uropathogens isolated from patients treated at the 34 Basic Health Units (UBS) in the city of São Bernardo do Campo. From a library, aptamers will be selected using the cell-SELEX technique. Once selected, aptamers will be identified using next-generation sequencing and the most frequent sequences will be synthesized and screened for specificity assessment by flow cytometry and fluorescence microscopy; and the bactericidal/bacteriostatic potential evaluated by time kill in clinical samples of uropathogens.