Immunization with genetic toxoids of the Arcanobacterium pyogenes cholesterol-dependent cytolysin, pyolysin, protects mice against infection.
Pyolysin (PLO), a cholesterol-dependent cytolysin expressed by Arcanobacterium pyogenes, is an important host-protective antigen. However, this molecule is toxic and requires inactivation prior to its use as a vaccine. Three genetically toxoided, nonhemolytic PLO molecules, HIS-PLO.F(497), HIS-PLO.Delta P(499), and HIS-PLO.A(522), were found to be nontoxic, and vaccinated mice were protected from infection, indicating the potential of these toxoids as vaccines. Furthermore, in a mouse model of infection, A. pyogenes carrying the F(497) mutation was as attenuated as a PLO-deficient strain, indicating that the cytolytic activity of PLO is important in virulence.
Jost
B Helen
BH
Department of Veterinary Science and Microbiology, The University of Arizona, Tucson, Arizona 85721, USA. jost@u.arizona.edu
Trinh
Hien T
HT
Songer
J Glenn
JG
Billington
Stephen J
SJ
D000191:Actinomycetaceae / Q000276:immunology* / Q000472:pathogenicity; D000818:Animals; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D001428:Bacterial Vaccines / Q000276:immunology*; D002784:Cholesterol / Q000502:physiology*; D003603:Cytotoxins / Q000276:immunology*; D006460:Hemolysin Proteins / Q000276:immunology*; D007114:Immunization; D051379:Mice; D008813:Mice, Inbred ICR; D014121:Toxoids / Q000276:immunology*; D014774:Virulence
D001426:Bacterial Proteins; D001427:Bacterial Toxins; D001428:Bacterial Vaccines; D003603:Cytotoxins; D006460:Hemolysin Proteins; C108448:Pyolysin, Arcanobacterium pyogenes; D014121:Toxoids; D002784:Cholesterol