Genetic analysis and genomic characterization of multidrug resistant bactéria: bacteriophage isolation and vaccine development for use in antimicrobial therapy

• Grant number: 22/16872-6
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2023
• End date: August 31, 2025
• Field of knowledge: Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
• Principal Investigator: Maria Cristina da Silva Pranchevicius
• Grantee: Maria Cristina da Silva Pranchevicius
• Host Institution: Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil
• Associated researchers: Anderson Ferreira da Cunha ; André Pitondo da Silva ; Louise Teixeira Cerdeira

Abstract

The rapid global spread of multi-drug resistant (MDR) bacteria and the lack of new antibiotics to treat infections caused by these organisms pose a threat to infection prevention and treatment protocols. Thus a better understanding of the pathogenesis and drug resistance profile are important to identify better targets and develop novel drugs to treat MDR bacteria. In this study, we will characterize the resistance and virulence profile of Klebsiella pneumoniae and Klebsiella oxytoca isolated from intensive care unit patient samples, using molecular techniques, whole genome sequencing, and bioinformatics tools. We will used extensive bioinformatic analyses based on reverse vaccinology and subtractive proteomics-based approach to predict potential drug targets and vaccine candidates against Enterobacter cloacae, an opportunistic pathogens found in hospital settings. We will perform cloning, expression and purification of a multi-epitope-based vaccine candidate against S. marcescens using insect cell and E. coli expression system. Furthermore, we will isolate and characterize lytic phages against S. marcescens e K. oxytoca, for future phage therapy applications and sanitation. Our data will provide important information that may contribute to the control of antibiotic resistance and dissemination of these pathogens. In addition, we will be able to contribute to the development of new therapeutic strategies against MDR bacteria of high clinical relevance. (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)

RODRIGUES, SAULO HENRIQUE; NUNES, GUSTAVO DANTAS; SOARES, GABRIELA GUERRERA; FERREIRA, ROUMAYNE LOPES; DAMAS, MARCELO SILVA FOLHAS; LAPREGA, PEDRO MENDES; SHILLING, REBECCA ELIZABETH; CAMPOS, LESLIE CAMELO; DA COSTA, ANDREA SOARES; MALAVAZI, IRAN; et al. First report of coexistence of blaKPC-2 and blaNDM-1 in carbapenem-resistant clinical isolates of Klebsiella aerogenes in Brazil. FRONTIERS IN MICROBIOLOGY, v. 15, p. 21-pg., 2024-02-14. (21/00425-8, 22/16872-6, 18/20697-0, 21/08423-4, 22/01223-2, 18/24213-7, 23/08917-2, 20/11964-4, 22/12429-0)