A hemolytic pigment of Group B Streptococcus allows bacterial penetration of human placenta

Whidbey, Christopher; Harrell, Maria I.; Burnside, Kellie; Ngo, Lisa Y.; Becraft, Alexis K.; Iyer, Lakshminarayan M.; Aravind, L.; Hitti, Jane; Waldorf, Kristina M. Adams; Rajagopal, Lakshmi

doi:10.1084/jem.20122753

Cited by 153 publications

(291 citation statements)

References 75 publications

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“…Up to 50% of patients surviving meningitis suffer from neurological problems (2). A GBS virulence factor that may substantially contribute to the pathogenesis of meningitis and sepsis is the poreforming toxin ␤-hemolysin, which is an ornithine rhamnolipid (3). Rhamnolipids, known as exotoxins in Pseudomonas spp, have pore-forming properties and may allow molecules such as nucleic acids to cross the phagosomal membrane.…”

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confidence: 99%

RNA and β-Hemolysin of Group B Streptococcus Induce Interleukin-1β (IL-1β) by Activating NLRP3 Inflammasomes in Mouse Macrophages

Gupta

Ghosh

Monks

et al. 2014

Journal of Biological Chemistry

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Background: Group B Streptococcus (GBS) activates the NLRP3 inflammasome. Results: GBS RNA escapes the phagolysosome and activates the NLRP3 inflammasome in a ␤-hemolysin-dependent fashion. RNA-NLRP3 interaction and activation are enhanced by lysosomal leakage. Conclusion: RNA activates the NLRP3 inflammasome in synergy with phagolysosomal proteins. Significance: The NLRP3 inflammasome responds to bacterial invasion via RNA recognition subsequent to phagolysosomal degradation.

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confidence: 99%

RNA and β-Hemolysin of Group B Streptococcus Induce Interleukin-1β (IL-1β) by Activating NLRP3 Inflammasomes in Mouse Macrophages

Gupta

Ghosh

Monks

et al. 2014

Journal of Biological Chemistry

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“…This ␤-h/c has a central role in balancing the pro-and anti-inflammatory responses of the infected host and is necessary to breach the epithelial and endothelial barriers and the phagolysosome membrane (10)(11)(12)(13)(14)(15). Remarkably, the GBS ␤-h/c is unique among Gram-positive pathogens and its production is linked to that of a characteristic orange-to-red pigment.…”

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confidence: 99%

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confidence: 99%

“…However, it was recently established that the ␤-h/c and the pigment correspond to a unique molecule called granadaene (9,11), a 676-Da ornithine rhamno-polyene (11,20). Granadaene may be entirely synthesized by the 12 genes of the cyl operon (11,19,21). It involves the initial synthesis of the ␤-h/c core lipid by AcpC, CylD, CylI, and CylG (i.e., the Cyl homologues of fatty acid synthesis enzymes) followed by addition of one ornithine and one rhamnose residue by CylE and CylJ, respectively (11).…”

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confidence: 99%

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Molecular Characterization of Nonhemolytic and Nonpigmented Group B Streptococci Responsible for Human Invasive Infections

et al. 2016

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h Group B Streptococcus (GBS) is a common commensal bacterium in adults, but is also the leading cause of invasive bacterial infections in neonates in developed countries. The ␤-hemolysin/cytolysin (␤-h/c), which is always associated with the production of an orange-to-red pigment, is a major virulence factor that is also used for GBS diagnosis. A collection of 1,776 independent clinical GBS strains isolated in France between 2006 and 2013 was evaluated on specific medium for ␤-h/c activity and pigment production. The genomic sequences of nonhemolytic and nonpigmented (NH/NP) strains were analyzed to identify the molecular basis of this phenotype. Gene deletions or complementations were carried out to confirm the genotype-phenotype association. Sixty-three GBS strains (3.5%) were NH/NP, and 47 of these (74.6%) originated from invasive infections, including bacteremia and meningitis, in neonates or adults. The mutations are localized predominantly in the cyl operon, encoding the ␤-h/c pigment biosynthetic pathway and, in the abx1 gene, encoding a CovSR regulator partner. In conclusion, although usually associated with GBS virulence, ␤-h/c pigment production is not absolutely required to cause human invasive infections. Caution should therefore be taken in the use of hemolysis and pigmentation as criteria for GBS diagnosis in routine clinical laboratory settings. S treptococcus agalactiae, or group B Streptococcus (GBS), is aGram-positive bacterium that is usually an asymptomatic member of the human intestinal and vaginal microbiota. However, GBS is also the leading cause of neonatal sepsis and meningitis in developed countries (1-3) and an emerging pathogen in adults, mostly in the elderly (4, 5). Neonatal infections occur predominantly during delivery by inhalation or ingestion of contaminated secretions of the mother's vagina. Rapid invasive infections may follow, with a mortality rate of up to 10% during the first week of life (early-onset disease [EOD], age of 0 to 6 days) or during the first 3 months of life (late-onset disease [LOD], age of 7 to 89 days). Systematic GBS screening prior to delivery and intrapartum antibiotic prophylaxis have efficiently reduced EOD but not LOD (6), highlighting the need to further improve the diagnosis and treatments.GBS is an extracellular pathogen and one of its characteristics is the secretion of a potent ␤-hemolysin/cytolysin (␤-h/c) (7-9). This ␤-h/c has a central role in balancing the pro-and anti-inflammatory responses of the infected host and is necessary to breach the epithelial and endothelial barriers and the phagolysosome membrane (10-15). Remarkably, the GBS ␤-h/c is unique among Gram-positive pathogens and its production is linked to that of a characteristic orange-to-red pigment. This dual and specific ␤-h/c and pigment phenotype is routinely used in clinical settings to identify GBS isolates (16,17).It was initially proposed that the GBS protein CylE was, in fact, ␤-h/c and that the pigment was a distinct carotenoid-like molecule (18,19). However, it was rece...

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“…GBS also may contribute to birth asphyxia, prematurity and stillbirths; a recent systematic review estimated that GBS might account for up to 12% of stillbirths 21 . In vitro and animal data demonstrate that components of GBS are capable of disrupting critical maternal-fetal barriers during pregnancy resulting in tissue damage and inflammatory changes and thereby the potential to precipitate preterm labour [22][23][24][25] . However, it is more difficult to clearly establish this relationship in humans and the evidence currently is mixed 26 .…”

Section: Natural Infection a Disease Burden Gbsmentioning

confidence: 99%

Group B streptococcus and respiratory syncytial virus immunisation during pregnancy: a landscape analysis

Heath

Culley

Jones

et al. 2017

The Lancet Infectious Diseases

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A hemolytic pigment of Group B Streptococcus allows bacterial penetration of human placenta

Abstract: Group B Streptococcus invades human amniotic epithelial cells using a hemolytic pigment.

Cited by 153 publications

References 75 publications

RNA and β-Hemolysin of Group B Streptococcus Induce Interleukin-1β (IL-1β) by Activating NLRP3 Inflammasomes in Mouse Macrophages

RNA and β-Hemolysin of Group B Streptococcus Induce Interleukin-1β (IL-1β) by Activating NLRP3 Inflammasomes in Mouse Macrophages

Molecular Characterization of Nonhemolytic and Nonpigmented Group B Streptococci Responsible for Human Invasive Infections

Group B streptococcus and respiratory syncytial virus immunisation during pregnancy: a landscape analysis

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