Determinants of the necrotic activity of exfoliative protein C (ExhC) from Staphylococcus sciuri

• Grant number: 19/10230-0
• Support Opportunities: Scholarships in Brazil - Master
• Start date: September 01, 2019
• End date: February 28, 2021
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Raghuvir Krishnaswamy Arni
• Grantee: Carolina Gismene
• 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

Abstract

Staphylococcus sciuri is a commensal and pathogenic bacterium with clinical and veterinary relevance. Recently, a strain of S. sciuri was described as the etiological agent of exudative epidermis in pigs in China and the main virulence factor is linked to clinical manifestation was the exfoliative protein C (ExhC). The ExhC of S. sciuri, in addition to triggering the epidermus in piglets and the newborn mice, was able to induce cellular necrosis in vitro, specifically in renal cell fibroblasts of newborn hamsters (BHK-21) a property previously unknown in exfoliative toxins (ETs). The use of recombinant ExhC fragments arrived at the conclusion that the domain which contains residues 79-128 is responsible for the observed necrotic activity. The objective of this study is to verify whether the mutations of these amino acid residues determine necrotic activity and to determine the structural details of this region and to correlate it with necrosis, to understand the mechanism of action and thus to evaluate the action of potential inhibitors. These experiments will also be performed with a chimeric ETD exfoliative protein, with the substitution of the corresponding region of amino acid residues 79-128 of the ExhC protein. (AU)