TY - JOUR
T1 - Group B streptococcal β-hemolysin induces mortality and liver injury in experimental sepsis
AU - Ring, Axel
AU - Braun, Johann S.
AU - Pohl, Jürgen
AU - Nizet, Victor
AU - Stremmel, Wolfgang
AU - Shenep, Jerry L.
N1 - Funding Information:
Financial support: National Institutes of Health (AI-27913 to J.L.S. and AI-01451 to V.N.); Cancer Support CORE grant (CA-21765 to St. Jude Children’s Research Hospital); American Lebanese Syrian Associated Charities.
PY - 2002/6/15
Y1 - 2002/6/15
N2 - 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 COHl:cylEΔcat (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 β-hemolysin triggers apoptotic pathways in hepatocytes. This work provides the first evidence that GBS β-hemolysin plays a crucial role in the pathophysiology of GBS sepsis by inducing liver failure and high mortality.
AB - 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 COHl:cylEΔcat (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 β-hemolysin triggers apoptotic pathways in hepatocytes. This work provides the first evidence that GBS β-hemolysin plays a crucial role in the pathophysiology of GBS sepsis by inducing liver failure and high mortality.
UR - http://www.scopus.com/inward/record.url?scp=0037097516&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037097516&partnerID=8YFLogxK
U2 - 10.1086/340818
DO - 10.1086/340818
M3 - Article
C2 - 12085320
AN - SCOPUS:0037097516
SN - 0022-1899
VL - 185
SP - 1745
EP - 1753
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 12
ER -