Abstract:
: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.
journal_name
EMBO Mol Medjournal_title
EMBO molecular medicineauthors
Whidbey C,Vornhagen J,Gendrin C,Boldenow E,Samson JM,Doering K,Ngo L,Ezekwe EA Jr,Gundlach JH,Elovitz MA,Liggitt D,Duncan JA,Adams Waldorf KM,Rajagopal Ldoi
10.15252/emmm.201404883subject
Has Abstractpub_date
2015-04-01 00:00:00pages
488-505issue
4eissn
1757-4676issn
1757-4684pii
emmm.201404883journal_volume
7pub_type
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