Open AccessA streptococcal lipid toxin induces membrane permeabilization and pyroptosis leading to fetal injury
Author(s) -
Whidbey Christopher,
Vornhagen Jay,
Gendrin Claire,
Boldenow Erica,
Samson Jenny Mae,
Doering Kenji,
Ngo Lisa,
Ezekwe Ejiofor A D,
Gundlach Jens H,
Elovitz Michal A,
Liggitt Denny,
Duncan Joseph A,
Adams Waldorf Kristina M,
Rajagopal Lakshmi
Publication year - 2015
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201404883
Subject(s) - pyroptosis , inflammasome , hemolysis , microbiology and biotechnology , biology , immunology , chemistry , inflammation
Group B streptococci ( GBS ) are Gram‐positive bacteria that cause infections in utero and in newborns. We recently showed that the GBS pigment is hemolytic and increased pigment production promotes bacterial penetration of human placenta. However, mechanisms utilized by the hemolytic pigment to induce host cell lysis and the consequence on fetal injury are not known. Here, we show that the GBS pigment induces membrane permeability in artificial lipid bilayers and host cells. Membrane defects induced by the GBS pigment trigger K + efflux leading to osmotic lysis of red blood cells or pyroptosis in human macrophages. Macrophages lacking the NLRP 3 inflammasome recovered from pigment‐induced cell damage. In a murine model of in utero infection, hyperpigmented GBS strains induced fetal injury in both an NLRP 3 inflammasome‐dependent and NLRP 3 inflammasome‐independent manner. These results demonstrate that the dual mechanism of action of the bacterial pigment/lipid toxin leading to hemolysis or pyroptosis exacerbates fetal injury and suggest that preventing both activities of the hemolytic lipid is likely critical to reduce GBS fetal injury and preterm birth.