Search for peptide ligands for inhibition against exfoliative toxin C (ExhC) from Mammaliicoccus sciuri via Phage Display

• Grant number: 23/05158-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2023
• End date: February 29, 2024
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Raghuvir Krishnaswamy Arni
• Grantee: Luís Eduardo de Almeida Passos Cerbino
• Host Institution: Instituto de Biociências, Letras e Ciências Exatas (IBILCE). Universidade Estadual Paulista (UNESP). Campus de São José do Rio Preto. São José do Rio Preto , SP, Brazil
• Associated research grant: 20/08615-8 - Protein exosites, cryptic sites and moonlighting: identification, functional mapping and effects of changes in structure, AP.TEM

Abstract

Mammaliicoccus sciuri is a pathogenic and commensal bacterium with clinical and veterinary importance. M. sciuri was described as the etiological agent of exudative epidermitis in swine and the main virulence factor involved was exfoliative toxin C (ExhC). M. sciuri ExhC also causes epidermal exfoliation in newborn mice, necrosis in renal fibroblasts in newborn hamsters, and inhibition of phagocytic action by RAW 264.7 macrophages. These last two properties are so far unknown for other exfoliative toxins (ETs) produced by bacteria of the genus Staphylococcus. The inhibition and death of RAW 264.7 macrophages decreased the phagocytosis of a M. sciuri strain by such cells. Cell death by necrosis generates an immune response in the host, involving the action of macrophages in the target tissue of necrosis. Recently, the production of recombinant ExhC fragments led to the conclusion that specific interactions in the domain containing certain amino acid residues are responsible for the necrotic activity. The alignment of amino acids in the necrotic domain with the corresponding regions of the other ETs indicated the presence of amino acid residues that are fully conserved or have similar biochemical properties in most ETs, except for M. sciuri ExhC. However, there are still unknown fragments and/or residues of ExhC amino acids involved in the death of RAW 264.7 macrophages. The main objective is to find peptide ligands, through the Phage Display technique, that can inhibit the different activities of ExhC, in addition to the search of partner cell proteins through the BLAST tool (Basic Local Alignment Search Tool) involved in these activities, in order to increase the understanding of their mechanisms of action. Thisproject is associated with the thematic project 2020/08615-8.