Determination of protein-protein interactions during phage infection

• Grant number: 24/03204-0
• Support Opportunities: Scholarships in Brazil - Master
• Start date: May 01, 2024
• End date: February 28, 2026
• Field of knowledge: Biological Sciences - Biochemistry - Biochemistry of Microorganisms
• Principal Investigator: Germán Gustavo Sgro
• Grantee: César Augusto Peña Llontop
• 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

Bacteriophages (phages) are bacterial viruses present in several and most diverse habitats. Through their interaction with receptors on the surface of target cells, they infect bacteria with high specificity and efficiency. Over the years, the use of phages as therapeutic agents (phage therapy) and in control strategies to combat bacterial diseases in crops (phage biocontrol) have gained representation, as these approaches have advantages over chemical controls. Virions have highly diverse though specific receptor-binding proteins (RBPs) for the bacterial receptors (T4P, LPS, outer membrane proteins, flagella, and others) whose identification presents a challenge. In addition to the RBPs, the success of the lytic infection also depends on overcoming anti-phage defence mechanisms (immunity) that may exist in the bacterium, achieved once the virion genome gets inside the host cell and is translated. Some phages recognize only one type of receptor (monovalent) while others can bind to variants of the same receptor type or to multiple different receptors (polyvalent). Most of the known phages recognize only one type of receptor and, therefore, have a limited range of bacterial strains susceptible to infection (narrow host-range). Phages evolve rapidly, and may eventually change their host range as a result of mutations in their RBPs or other genes. In comparison, the adaptation mechanisms of bacteria to evade phage recognition and infection are slow, as they involve profound changes in the structures of surface components that must be reflected in their genomes and without loss of biological functionality. The identification of determinants for specific phage-bacteria interactions, as well as the understanding of the molecular mechanisms of the anti-phage defence systems, are fundamental for the designing of new strategies for the use of phages as antimicrobial agents to control microorganisms of interest. In this project we propose to determine and study protein-protein interaction networks in less trained phage:bacteria systems, where bacterial species have an impact on human health and agriculture.