Exfoliative Toxin C (ExhC) from Mammaliicoccus sciuri: investigation of multiple activities

• Grant number: 24/03185-6
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: April 01, 2024
• End date: May 31, 2027
• 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

The bacterium Staphylococcus sciuri (recently reclassified as Mammaliicoccus sciuri) is the etiological agent of exudative epidermitis in pigs, mainly due to the activity of the Exfoliative Toxin C (ExhC). This toxin also causes epidermal exfoliation in newborn rats, necrosis in newborn hamster renal fibroblasts (BHK-21 cells), and inhibition of phagocytosis by macrophages (RAW 264.7) in mice. The latter two properties are still unknown for other exfoliative toxins from Staphylococcus bacteria. The immune response generated by cellular necrosis involves the action of macrophages in the target tissue of necrosis. The residues of ExhC responsible for necrotic activity have been previously identified and are located in a site independent of the active site. Mutations in these residues (R47A, N49F, Q51K, and R89A) lead to the loss of necrotic activity but do not affect exfoliative activity. However, the fragments and/or amino acid residues of ExhC involved in the activity observed for RAW 264.7 are still unknown. Through Phage Display technology, the main objective is to find peptide ligands that can modulate the activities of ExhC. The interactions of the identified ligands with the protein will be evaluated using biophysical and structural biology techniques. This project is linked to thematic project 2020/08615-8.