Identification of a Key Residue for Oligomerisation and Pore-Formation of Clostridium perfringens NetB
Sérgio P. Fernandes da Costa,
Christos G. Savva,
Monika Bokori-Brown,
Claire E. Naylor,
David S. Moss,
Ajit K. Basak,
Richard W. Titball
Affiliations
Sérgio P. Fernandes da Costa
College of Life and Environmental Sciences, University of Exeter, Stocker Road, Exeter EX4 4QD, UK
Christos G. Savva
Department of Biological Sciences, School of Crystallography, Institute of Structural and Molecular Biology, Birkbeck College, Malet Street, London WC1E 7HX, UK
Monika Bokori-Brown
College of Life and Environmental Sciences, University of Exeter, Stocker Road, Exeter EX4 4QD, UK
Claire E. Naylor
Department of Biological Sciences, School of Crystallography, Institute of Structural and Molecular Biology, Birkbeck College, Malet Street, London WC1E 7HX, UK
David S. Moss
Department of Biological Sciences, School of Crystallography, Institute of Structural and Molecular Biology, Birkbeck College, Malet Street, London WC1E 7HX, UK
Ajit K. Basak
Department of Biological Sciences, School of Crystallography, Institute of Structural and Molecular Biology, Birkbeck College, Malet Street, London WC1E 7HX, UK
Richard W. Titball
College of Life and Environmental Sciences, University of Exeter, Stocker Road, Exeter EX4 4QD, UK
Necrotic enteritis toxin B (NetB) is a β-pore-forming toxin produced by Clostridium perfringens and has been identified as a key virulence factor in the pathogenesis of avian necrotic enteritis, a disease causing significant economic damage to the poultry industry worldwide. In this study, site-directed mutagenesis was used to identify amino acids that play a role in NetB oligomerisation and pore-formation. NetB K41H showed significantly reduced toxicity towards LMH cells and human red blood cells relative to wild type toxin. NetB K41H was unable to oligomerise and form pores in liposomes. These findings suggest that NetB K41H could be developed as a genetic toxoid vaccine to protect against necrotic enteritis.
