A streptococcal lipid toxin induces membrane permeabilization and pyroptosis leading to fetal injury

EMBO Mol Med. 2015 Apr;7(4):488-505. doi: 10.15252/emmm.201404883.


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 NLRP3 inflammasome recovered from pigment-induced cell damage. In a murine model of in utero infection, hyperpigmented GBS strains induced fetal injury in both an NLRP3 inflammasome-dependent and NLRP3 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.

Keywords: Group B streptococcus; cell death; hemolytic pigment; inflammasome; preterm birth.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Toxins* / immunology
  • Bacterial Toxins* / toxicity
  • Cell Line, Tumor
  • Cell Membrane Permeability*
  • Female
  • Fetal Diseases* / immunology
  • Fetal Diseases* / microbiology
  • Fetal Diseases* / pathology
  • Humans
  • Male
  • Membrane Lipids* / immunology
  • Membrane Lipids* / toxicity
  • Mice
  • Mice, Knockout
  • Pyroptosis / immunology*
  • Streptococcal Infections* / immunology
  • Streptococcal Infections* / pathology
  • Streptococcus agalactiae* / immunology
  • Streptococcus agalactiae* / pathogenicity


  • Bacterial Toxins
  • Membrane Lipids