Development of a platform for rational modification of bacteriophages

• Grant number: 24/15010-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2024
• End date: September 30, 2025
• Field of knowledge: Biological Sciences - Microbiology
• Principal Investigator: Germán Gustavo Sgro
• Grantee: Helena de Andrade Barbosa Guilherme
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 22/03018-7 - Structural, molecular and functional characterization of bacteriophages associated with bacteria of medical and agricultural interest, AP.PNGP.PI

Abstract

Currently, bacteria that are multi-resistant to conventional treatments pose a worldwide health problem. The medicinal antibiotics used have few structural differences, making it easy for new cases of resistance to arise. Therefore, new treatment proposals must be carefully developed and explored. In this regard, the study of bacteriophages is on the rise. Bacteriophages, or phages, are highly specific viruses that infect bacteria: a virus strain typically infects only one bacterial strain. This is an advantage over medications, as it allows only the bacteria of interest to be eliminated, theoretically causing little or no alteration to the individual's (beneficial) microbiota. In this aspect, phage therapy (the use of phages to control and eradicate an infection) seeks to develop methodologies to rationally modify this specificity so that a phage can infect more than one pathogenic bacterium, through modifications to viral structures. However, there are still few studies that address genetic changes in phages. Therefore, this study aims to develop a methodology for rational modification, as well as to test and study the success of introducing mutations in structural parts (head, nozzle, tail) of the bacteriophage ¦Xacm4-11, a virus that infects the phytopathogenic bacterium Xanthomonas citri. The methodology is based on the use of homologous recombination and selection by CRISPR, a procedure recently addressed in the literature, and will facilitate the creation of a platform for the rational modification of infectious bacteriophages of this and other species of interest.