Group B Streptococcus circumvents neutrophils and neutrophil extracellular traps during amniotic cavity invasion and preterm labor

2016 ◽  
Vol 1 (4) ◽  
Author(s):  
Erica Boldenow ◽  
Claire Gendrin ◽  
Lisa Ngo ◽  
Craig Bierle ◽  
Jay Vornhagen ◽  
...  
Keyword(s):  
Preterm Labor ◽  
Group B Streptococcus ◽  
Neutrophil Extracellular Traps ◽  
Amniotic Cavity ◽  
Extracellular Traps ◽  
Group B

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

2013 ◽  
Vol 210 (6) ◽  
pp. 1265-1281 ◽  
Author(s):  
Christopher Whidbey ◽  
Maria Isabel Harrell ◽  
Kellie Burnside ◽  
Lisa Ngo ◽  
Alexis K. Becraft ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Amniotic Fluid ◽  
Preterm Labor ◽  
Group B Streptococcus ◽  
Dependent Manner ◽  
Microbial Infection ◽  
Amniotic Cavity ◽  
Protein Toxin ◽  
Ascending Infection ◽  
Group B

Microbial infection of the amniotic fluid is a significant cause of fetal injury, preterm birth, and newborn infections. Group B Streptococcus (GBS) is an important human bacterial pathogen associated with preterm birth, fetal injury, and neonatal mortality. Although GBS has been isolated from amniotic fluid of women in preterm labor, mechanisms of in utero infection remain unknown. Previous studies indicated that GBS are unable to invade human amniotic epithelial cells (hAECs), which represent the last barrier to the amniotic cavity and fetus. We show that GBS invades hAECs and strains lacking the hemolysin repressor CovR/S accelerate amniotic barrier failure and penetrate chorioamniotic membranes in a hemolysin-dependent manner. Clinical GBS isolates obtained from women in preterm labor are hyperhemolytic and some are associated with covR/S mutations. We demonstrate for the first time that hemolytic and cytolytic activity of GBS is due to the ornithine rhamnolipid pigment and not due to a pore-forming protein toxin. Our studies emphasize the importance of the hemolytic GBS pigment in ascending infection and fetal injury.

scholarly journals Streptococcus agalactiae Induces Placental Macrophages To Release Extracellular Traps Loaded with Tissue Remodeling Enzymes via an Oxidative Burst-Dependent Mechanism

mBio ◽  
2018 ◽  
Vol 9 (6) ◽  
Author(s):  
Ryan S. Doster ◽  
Jessica A. Sutton ◽  
Lisa M. Rogers ◽  
David M. Aronoff ◽  
Jennifer A. Gaddy
Keyword(s):  
Bacterial Infection ◽  
Streptococcus Agalactiae ◽  
Preterm Labor ◽  
Fetal Membrane ◽  
Content Type ◽  
Membrane Rupture ◽  
Extracellular Traps ◽  
Placental Macrophages ◽  
Group B ◽  
Placental Macrophage

ABSTRACT Streptococcus agalactiae, or group B Streptococcus (GBS), is a common perinatal pathogen. GBS colonization of the vaginal mucosa during pregnancy is a risk factor for invasive infection of the fetal membranes (chorioamnionitis) and its consequences such as membrane rupture, preterm labor, stillbirth, and neonatal sepsis. Placental macrophages, or Hofbauer cells, are fetally derived macrophages present within placental and fetal membrane tissues that perform vital functions for fetal and placental development, including supporting angiogenesis, tissue remodeling, and regulation of maternal-fetal tolerance. Although placental macrophages as tissue-resident innate phagocytes are likely to engage invasive bacteria such as GBS, there is limited information regarding how these cells respond to bacterial infection. Here, we demonstrate in vitro that placental macrophages release macrophage extracellular traps (METs) in response to bacterial infection. Placental macrophage METs contain proteins, including histones, myeloperoxidase, and neutrophil elastase similar to neutrophil extracellular traps, and are capable of killing GBS cells. MET release from these cells occurs by a process that depends on the production of reactive oxygen species. Placental macrophage METs also contain matrix metalloproteases that are released in response to GBS and could contribute to fetal membrane weakening during infection. MET structures were identified within human fetal membrane tissues infected ex vivo, suggesting that placental macrophages release METs in response to bacterial infection during chorioamnionitis. IMPORTANCE Streptococcus agalactiae, also known as group B Streptococcus (GBS), is a common pathogen during pregnancy where infection can result in chorioamnionitis, preterm premature rupture of membranes (PPROM), preterm labor, stillbirth, and neonatal sepsis. Mechanisms by which GBS infection results in adverse pregnancy outcomes are still incompletely understood. This study evaluated interactions between GBS and placental macrophages. The data demonstrate that in response to infection, placental macrophages release extracellular traps capable of killing GBS. Additionally, this work establishes that proteins associated with extracellular trap fibers include several matrix metalloproteinases that have been associated with chorioamnionitis. In the context of pregnancy, placental macrophage responses to bacterial infection might have beneficial and adverse consequences, including protective effects against bacterial invasion, but they may also release important mediators of membrane breakdown that could contribute to membrane rupture or preterm labor.

scholarly journals Heparan Sulfate Modulates Neutrophil and Endothelial Function in Antibacterial Innate Immunity

2015 ◽  
Vol 83 (9) ◽  
pp. 3648-3656 ◽  
Author(s):  
Ding Xu ◽  
Joshua Olson ◽  
Jason N. Cole ◽  
Xander M. van Wijk ◽  
Volker Brinkmann ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Heparan Sulfate ◽  
Bactericidal Activity ◽  
Bacterial Pathogen ◽  
Systemic Infection ◽  
Neutrophil Extracellular Traps ◽  
Content Type ◽  
Extracellular Traps ◽  
The Central Nervous System ◽  
Group B

Recently, we showed that endothelial heparan sulfate facilitates entry of a bacterial pathogen into the central nervous system. Here, we show that normal bactericidal activity of neutrophils is influenced by the sulfation pattern of heparan sulfate. Inactivation of heparan sulfate uronyl 2-O-sulfotransferase (Hs2st) in neutrophils substantially reduced their bactericidal activity, and Hs2st deficiency rendered mice more susceptible to systemic infection with the pathogenic bacterium group BStreptococcus. Specifically, altered sulfation of heparan sulfate in mutant neutrophils affected formation of neutrophil extracellular traps while not influencing phagocytosis, production of reactive oxygen species, or secretion of granular proteases. Heparan sulfate proteoglycan(s) is present in neutrophil extracellular traps, modulates histone affinity, and modulates their microbial activity. Hs2st-deficient brain endothelial cells show enhanced binding to group BStreptococcusand are more susceptible to apoptosis, likely contributing to the observed increase in dissemination of group BStreptococcusinto the brain of Hs2st-deficient mice following intravenous challenge. Taken together, our data provide strong evidence that heparan sulfate from both neutrophils and the endothelium plays important roles in modulating innate immunity.

scholarly journals Neutrophil Extracellular Traps in the Amniotic Cavity of Women with Intra-Amniotic Infection: A New Mechanism of Host Defense

2016 ◽  
Vol 24 (8) ◽  
pp. 1139-1153 ◽  
Author(s):  
Nardhy Gomez-Lopez ◽  
Roberto Romero ◽  
Yi Xu ◽  
Derek Miller ◽  
Ronald Unkel ◽  
...  
Keyword(s):  
Host Defense ◽  
Neutrophil Extracellular Traps ◽  
Amniotic Cavity ◽  
Extracellular Traps

DNA Probe for β-Hemolytic Group B Streptococcus : Diagnostic Accuracy in Threatened Preterm Labor

2000 ◽  
Vol 55 (2) ◽  
pp. 82
Author(s):  
Kristin M. Ryan ◽  
Shaun G. Lencki ◽  
B. Laurel Elder ◽  
William I. Northern ◽  
Harry J. Khamis ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Preterm Labor ◽  
Group B Streptococcus ◽  
Dna Probe ◽  
Threatened Preterm Labor ◽  
Group B

scholarly journals Hyaluronidase Impairs Neutrophil Function and Promotes Group B Streptococcus Invasion and Preterm Labor in Nonhuman Primates

mBio ◽  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Michelle Coleman ◽  
Blair Armistead ◽  
Austyn Orvis ◽  
Phoenicia Quach ◽  
Alyssa Brokaw ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Preterm Labor ◽  
Bacterial Invasion ◽  
Group B Streptococci ◽  
Primate Model ◽  
Amniotic Cavity ◽  
Human Pregnancy ◽  
Lower Genital Tract ◽  
Group B ◽  
Maternal Fetal Interface

ABSTRACT Invasive bacterial infections during pregnancy are a major risk factor for preterm birth, stillbirth, and fetal injury. Group B streptococci (GBS) are Gram-positive bacteria that asymptomatically colonize the lower genital tract but infect the amniotic fluid and induce preterm birth or stillbirth. Experimental models that closely emulate human pregnancy are pivotal for the development of successful strategies to prevent these adverse pregnancy outcomes. Using a unique nonhuman primate model that mimics human pregnancy and informs temporal events surrounding amniotic cavity invasion and preterm labor, we show that the animals inoculated with hyaluronidase (HylB)-expressing GBS consistently exhibited microbial invasion into the amniotic cavity, fetal bacteremia, and preterm labor. Although delayed cytokine responses were observed at the maternal-fetal interface, increased prostaglandin and matrix metalloproteinase levels in these animals likely mediated preterm labor. HylB-proficient GBS dampened reactive oxygen species production and exhibited increased resistance to neutrophils compared to an isogenic mutant. Together, these findings demonstrate how a bacterial enzyme promotes GBS amniotic cavity invasion and preterm labor in a model that closely resembles human pregnancy. IMPORTANCE Group B streptococci (GBS) are bacteria that commonly reside in the female lower genital tract as asymptomatic members of the microbiota. However, during pregnancy, GBS can infect tissues at the maternal-fetal interface, leading to preterm birth, stillbirth, or fetal injury. Understanding how GBS evade host defenses during pregnancy is key to developing improved preventive therapies for these adverse outcomes. In this study, we used a unique nonhuman primate model to show that an enzyme secreted by GBS, hyaluronidase (HylB) promotes bacterial invasion into the amniotic cavity and fetus. Although delayed immune responses were seen at the maternal-fetal interface, animals infected with hyaluronidase-expressing GBS exhibited premature cervical ripening and preterm labor. These observations reveal that HylB is a crucial GBS virulence factor that promotes bacterial invasion and preterm labor in a pregnancy model that closely emulates human pregnancy. Therefore, hyaluronidase inhibitors may be useful in therapeutic strategies against ascending GBS infection.

scholarly journals Streptococcus agalactiae induces placental macrophages to release extracellular traps loaded with tissue remodeling enzymes via an oxidative-burst-dependent mechanism

2018 ◽  
Author(s):  
Ryan S. Doster ◽  
Jessica A. Sutton ◽  
Lisa M. Rogers ◽  
David M. Aronoff ◽  
Jennifer A. Gaddy
Keyword(s):  
Bacterial Infection ◽  
Streptococcus Agalactiae ◽  
Neonatal Sepsis ◽  
Preterm Labor ◽  
Fetal Membrane ◽  
Membrane Rupture ◽  
Extracellular Traps ◽  
Placental Macrophages ◽  
Group B ◽  
Placental Macrophage

AbstractStreptococcus agalactiae, or Group B Streptococcus (GBS), is a common perinatal pathogen. GBS colonization of the vaginal mucosa during pregnancy is a risk factor for invasive infection of the fetal membranes (chorioamnionitis) and its consequences such as membrane rupture, preterm labor, stillbirth, and neonatal sepsis. Placental macrophages, or Hofbauer cells, are fetally-derived macrophages present within placental and fetal membrane tissues that perform vital functions for fetal and placental development, including supporting angiogenesis, tissue remodeling, and regulation of maternal-fetal tolerance. Although placental macrophages, as tissue-resident innate phagocytes, are likely to engage invasive bacteria such as GBS, there is limited information regarding how these cells respond to bacterial infection. Here, we demonstrate in vitro that placental macrophages release macrophage extracellular traps (METs) in response to bacterial infection. Placental macrophage METs contain proteins including histones, myeloperoxidase, and neutrophil elastase similar to neutrophil extracellular traps and are capable of killing GBS cells. MET release from these cells occurs by a process that depends on the production of reactive oxygen species. Placental macrophage METs also contain matrix metalloproteases that are released in response to GBS and could contribute to fetal membrane weakening during infection. MET structures were identified within human fetal membrane tissues infected ex vivo, suggesting that placental macrophages release METs in response to bacterial infection during chorioamnionitis.ImportanceStreptococcus agalactiae, also known as Group B Streptococcus (GBS), is a common pathogen during pregnancy where infection can result in chorioamnionitis, preterm premature rupture of membranes (PPROM), preterm labor, stillbirth, and neonatal sepsis. Mechanisms by which GBS infection results in adverse pregnancy outcomes are still incompletely understood. This study evaluated interactions between GBS and placental macrophages. The data demonstrate that in response to infection, placental macrophages release extracellular traps capable of killing GBS. Additionally, this work establishes that proteins associated with extracellular trap fibers include several matrix metalloproteinases that have been associated with chorioamnionitis. In the context of pregnancy, placental macrophage responses to bacterial infection might have beneficial and adverse consequences, including protective effects against bacterial invasion but also releasing important mediators of membrane breakdown that could contribute to membrane rupture or preterm labor.

scholarly journals Comparison of Culture and Rapid Enzyme Immunoassay for the Detection of Group B Streptococcus in High-Risk Pregnancies

1994 ◽  
Vol 2 (3) ◽  
pp. 115-119
Author(s):  
Mara J. Dinsmoor ◽  
Harry P. Dalton ◽  
Thomas C. C. Peng ◽  
James T. Christmas ◽  
Sousan Sayahtaheri-Altaie ◽  
...  
Keyword(s):  
High Risk ◽  
Predictive Value ◽  
Preterm Labor ◽  
Group B Streptococcus ◽  
Premature Rupture ◽  
Rapid Assay ◽  
Preterm Premature Rupture ◽  
Risk Patients ◽  
Group B ◽  
Sensitivity Specificity

Objective:The purpose of this study was to evaluate the Equate Strep B® test for clinical use in patients at high risk for complications from group B streptococcus (GBS) disease.Methods:Vaginoperineal swabs were obtained from patients with preterm premature rupture of the membranes and/or preterm labor and semiquantitative GBS cultures and Equate® assay were performed.Results:From May 14, 1990, to April 30, 1992, 650 patients were enrolled; 626 had both culture and Equate® results available, of whom 24% were colonized with GBS. The sensitivity, specificity, positive predictive value, and negative predictive value of the rapid assay were 28%, 84%, 35%, and 79%, respectively. Although the prevalence of GBS was higher in patients with ruptured membranes compared with those with intact membranes, rupture of membranes did not affect test sensitivity or specificity.Conclusions:We conclude that the Equate® rapid assay is not a sensitive method of GBS detection in high-risk patients.

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