Structural, molecular and functional characterization of bacteriophages associated with bacteria of medical and agricultural interest

• Grant number: 22/03018-7
• Support Opportunities: Research Grants - Initial Project
• Start date: July 01, 2023
• End date: June 30, 2028
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Germán Gustavo Sgro
• Grantee: Germán Gustavo Sgro
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated researchers: Aline Maria da Silva ; Henrique Ferreira ; Shaker Chuck Farah
• Associated scholarship(s): 24/14944-5 - Structural and functional studies of the bacteria-phage interface by cryoelectron tomography, BP.DD; 24/15010-6 - Development of a platform for rational modification of bacteriophages, BP.IC; 24/16240-5 - Production and purification of xanthomonas citri minicells for use in cryoelectron tomography (cryo-ET), BP.IC; 24/03204-0 - Determination of protein-protein interactions during phage infection, BP.MS

Abstract

Bacteriophages (phages) are viruses that infect bacteria, and are the smallest and most abundant biological entities on Earth. To replicate, they use the bacterial host machinery to either i) immediately produce new progeny after infection which leads to the death of the infected cell (lytic pathway), or ii) integrate into the bacterial chromosome as a prophage which allows establish a symbiotic relationship between the parties (lysogenic pathway). Studies in phage biology have brought enormous knowledge to areas such as molecular biology and genetics, demonstrating an amazing diversity of molecular mechanisms of interaction, infection and replication. The interaction begins with the recognition and adsorption of the phage on the surface of the bacterium, which determines the specificity and range of hosts. Most known phages have a narrow host range, usually infecting specific strains or isolates of a particular bacterial species. For such recognition, virions have specific proteins that bind to receptors located on the bacterial surface, being the most commonly used: lipopolysaccharides, exopolysaccharides, outer membrane proteins, fimbriae, pili and flagella. In recent decades, the interest in the use of phages as therapeutic agents (phage therapy) in the biological control of infections by multidrug-resistant bacteria has increased, as well as in the development of strategies for the biocontrol of pathogenic species in agricultural crops. In this context, understanding the molecular mechanisms underlying phage-bacteria interactions is crucial to obtain information on how phages affect microbial populations and how they can be used in clinical and biotechnological applications. In the present project, we propose to study the molecular structures, delve into the physiological relevance and obtain a deep understanding of the functioning of lytic bacteriophages that interact and infect bacterial strains of relevance in medicine and agriculture. (AU)