Role of streptococcal pyrogenic exotoxin B in the mouse model of group A streptococcal infection.
Streptococcal pyrogenic exotoxin B (SPE B) is a cysteine protease produced by Streptococcus pyogenes. In this study, the differences in virulence between protease-positive clinical isolates and their protease-negative mutants were examined in a mouse model. Isogenic protease-negative mutants were constructed by homologous recombination, using integrational plasmids to disrupt the speB gene. These mutants caused less mortality and tissue damage than protease-positive strains when inoculated into BALB/c mice via air pouch, suggesting that SPE B cysteine protease plays an important role in the pathogenesis of S. pyogenes infection. Reconstitution of SPE B in the air pouches increased the mortality of mice receiving the speB mutant strain. Infiltrated cell numbers in the exudates from the air pouches of mice infected with SPE B-producing S. pyogenes were higher than those from mice infected with protease-negative mutants at 12 h. However, despite pretreatment with vinblastine to deplete neutrophils, injection of protease-positive bacteria still resulted in severe tissue injury, indicating that neutrophil infiltration may not be the major factor involved in SPE B-enhanced tissue damage. The role of SPE B was further confirmed by demonstrating that SPE B immunization of mice conferred protection from challenge with a lethal dose of protease-positive bacteria.
Kuo
C F
CF
Departments of Microbiology and Immunology, National Cheng Kung University Medical College, Tainan, Taiwan, Republic of China.
Wu
J J
JJ
Lin
K Y
KY
Tsai
P J
PJ
Lee
S C
SC
Jin
Y T
YT
Lei
H Y
HY
Lin
Y S
YS
D000818:Animals; D001426:Bacterial Proteins; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D004195:Disease Models, Animal; D005098:Exotoxins / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D007116:Immunization, Passive; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D011817:Rabbits; D013290:Streptococcal Infections / Q000473:pathology* / Q000517:prevention & control; D013297:Streptococcus pyogenes / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology*; D014611:Vaccination; D014774:Virulence
D001426:Bacterial Proteins; D005098:Exotoxins; D008565:Membrane Proteins; C117980:SpeA protein, Streptococcus pyogenes; C027951:erythrogenic toxin; D003546:Cysteine Endopeptidases