Group B streptococcal beta-hemolysin induces mortality and liver injury in experimental sepsis.
New Zealand White rabbits were challenged with the wild-type (wt) group B streptococci (GBS) serotype III strain (COH1) and its isogenic nonhemolytic (NH) and hyperhemolytic (HH) mutants. Mortality differed significantly between rabbits infected with the HH mutant IN40 (67%), compared with rabbits infected with the wt COH1 strain (27%) and the NH strains COH1-20 and COH1:cylEDeltacat (13% and 0%, respectively; P<.05). Histopathologically, disseminated septic microabscesses surrounded by necrotic foci were found exclusively in the livers of HH mutant IN40-infected animals. Serum transaminase levels were 20-fold higher in the HH-infected group, compared with rabbits infected with the other strains. Positive TUNEL (in situ terminal deoxynucleotide transferase-mediated dUTP nick end labeling) staining and activation of caspase-3 in hepatocytes were more frequent in HH-infected than in wt-infected animals and absent in the NH mutant COH1-20-infected group, indicating that GBS beta-hemolysin triggers apoptotic pathways in hepatocytes. This work provides the first evidence that GBS beta-hemolysin plays a crucial role in the pathophysiology of GBS sepsis by inducing liver failure and high mortality.
Ring
Axel
A
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. axel_ring@med.uni-heidelberg.de
Braun
Johann S
JS
Pohl
Jürgen
J
Nizet
Victor
V
Stremmel
Wolfgang
W
Shenep
Jerry L
JL
D000818:Animals; D001426:Bacterial Proteins; D001794:Blood Pressure / Q000187:drug effects; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D004789:Enzyme Activation; D006460:Hemolysin Proteins / Q000633:toxicity*; D020287:In Situ Nick-End Labeling; D008099:Liver / Q000187:drug effects*; D011817:Rabbits; D012772:Shock, Septic / Q000401:mortality*; D013292:Streptococcus agalactiae; D000637:Transaminases / Q000097:blood
D001426:Bacterial Proteins; D006460:Hemolysin Proteins; C071495:streptococcal group B hemolysin; D000637:Transaminases; D053148:Caspase 3; D020169:Caspases