scholarly journals Bacterial Hyaluronidase Promotes Ascending GBS Infection and Preterm Birth

mBio ◽  
2016 ◽  
Vol 7 (3) ◽  
Author(s):  
Jay Vornhagen ◽  
Phoenicia Quach ◽  
Erica Boldenow ◽  
Sean Merillat ◽  
Christopher Whidbey ◽  
...  

ABSTRACT Preterm birth increases the risk of adverse birth outcomes and is the leading cause of neonatal mortality. A significant cause of preterm birth is in utero infection with vaginal microorganisms. These vaginal microorganisms are often recovered from the amniotic fluid of preterm birth cases. A vaginal microorganism frequently associated with preterm birth is group B streptococcus (GBS), or Streptococcus agalactiae . However, the molecular mechanisms underlying GBS ascension are poorly understood. Here, we describe the role of the GBS hyaluronidase in ascending infection and preterm birth. We show that clinical GBS strains associated with preterm labor or neonatal infections have increased hyaluronidase activity compared to commensal strains obtained from rectovaginal swabs of healthy women. Using a murine model of ascending infection, we show that hyaluronidase activity was associated with increased ascending GBS infection, preterm birth, and fetal demise. Interestingly, hyaluronidase activity reduced uterine inflammation but did not impact placental or fetal inflammation. Our study shows that hyaluronidase activity enables GBS to subvert uterine immune responses, leading to increased rates of ascending infection and preterm birth. These findings have important implications for the development of therapies to prevent in utero infection and preterm birth. IMPORTANCE GBS are a family of bacteria that frequently colonize the vagina of pregnant women. In some cases, GBS ascend from the vagina into the uterine space, leading to fetal injury and preterm birth. Unfortunately, little is known about the mechanisms underlying ascending GBS infection. In this study, we show that a GBS virulence factor, HylB, shows higher activity in strains isolated from cases of preterm birth than those isolates from rectovaginal swabs of healthy women. We discovered that GBS rely on HylB to avoid immune detection in uterine tissue, but not placental tissue, which leads to increased rates of fetal injury and preterm birth. These studies provide novel insight into the underlying mechanisms of ascending infection.

2013 ◽  
Vol 210 (6) ◽  
pp. 1265-1281 ◽  
Author(s):  
Christopher Whidbey ◽  
Maria Isabel Harrell ◽  
Kellie Burnside ◽  
Lisa Ngo ◽  
Alexis K. Becraft ◽  
...  

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.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sho Tano ◽  
Takuji Ueno ◽  
Michinori Mayama ◽  
Takuma Yamada ◽  
Takehiko Takeda ◽  
...  

Abstract Background Although infection and inflammation within the genital tract during pregnancy is considered a major risk factor for spontaneous preterm birth (PTB), there are few studies on association between vaginal microorganisms in the early stage of pregnancy and PTB. The aim of this study was to investigate relationship between vaginal Group B streptococcus (GBS) colonization, a leading cause of infection during pregnancy, in the early stage of pregnancy and PTB. Methods This single-center, retrospective cohort study utilized data from 2009 to 2017 obtained at TOYOTA Memorial Hospital. Women with singleton pregnancies who underwent vaginal culture around 14 weeks of gestation during their routine prenatal check-up were included. Vaginal sampling for Gram staining and culture was performed regardless of symptoms. GBS colonization was defined as positive for GBS latex agglutination assay. Statistical analysis was performed to determine the factors associated with PTB. Results Overall 1079 singleton pregnancies were included. GBS (5.7%) and Candida albicans (5.5%) were the most frequently observed microorganisms. The incidence of PTB (before 34 and before 37 weeks of gestation) were significantly higher in the GBS-positive group than in the GBS-negative group (6.6% vs 0.5%, p = 0.001 and 9.8% vs 4.3%, p = 0.047). Our multivariable logistic regression analysis revealed that GBS colonization was a factor associated with PTB before 34 and before 37 weeks of gestation (Odds ratio [OR] 15.17; 95% confidence interval [CI] 3.73–61.74), and OR 2.42; 95%CI 1.01–5.91, respectively). Conclusions The present study found that vaginal GBS colonization in the early stage of pregnancy was associated with PTB. Our study indicates that patients at a high risk for PTB can be extracted by a simple method using conventional culture method.


2018 ◽  
Vol 69 (1) ◽  
pp. 17-22 ◽  
Author(s):  
Marie‐Julie Allard ◽  
Marie‐Elsa Brochu ◽  
Julie D. Bergeron ◽  
Guillaume Sebire

2017 ◽  
Vol 65 (suppl_2) ◽  
pp. S133-S142 ◽  
Author(s):  
Fiorella Bianchi-Jassir ◽  
Anna C Seale ◽  
Maya Kohli-Lynch ◽  
Joy E Lawn ◽  
Carol J Baker ◽  
...  

2018 ◽  
Vol 128 (5) ◽  
pp. 1985-1999 ◽  
Author(s):  
Jay Vornhagen ◽  
Blair Armistead ◽  
Verónica Santana-Ufret ◽  
Claire Gendrin ◽  
Sean Merillat ◽  
...  

2018 ◽  
Vol 22 (3) ◽  
pp. 229-235 ◽  
Author(s):  
Pawel T Schubert ◽  
Deidre Mason ◽  
Roosacelis Martines ◽  
Marlene Deleon-Carnes ◽  
Sherif R Zaki ◽  
...  

Fetal bacterial infections are a common cause of fetal/neonatal morbidity and mortality. The pathologic correlates of congenital bacterial infection include acute chorioamnionitis, acute villitis, and acute intervillositis. The strength of the association of congenital bacterial infection differs among these pathologies. Acute chorioamnionitis results usually from an ascending infection, and damage to the fetus is thought to be cytokine driven rather than damage secondary to bacteremia. Acute villitis is strongly associated with fetal sepsis due to congenital infections. A much less common variant on acute villitis pattern has been described with additional presence of bacteria in the fetal capillaries of the chorionic villi. We describe the spectrum of bacteria that would induce this unique pattern. The histological archives were searched from 2 institutions for cases with intravascular bacteria present in the villous capillaries of the placenta. Thirteen cases were identified, of which 11 cases had acute chorioamnionitis and all cases showed an acute villitis. Eight cases had Escherichia coli identified and 3 cases had Group B Streptococcus. All cases were associated with fetal death. In 9 cases, the mother showed signs of a significant infection including 1 maternal death. We conclude that finding intravascular bacteria is a serious complication of congenital infection with serious fetal and maternal sequela.


Author(s):  
Lawrence Impey

Maternal illness is often more severe in pregnancy, e.g. varicella, malaria, and the treatment of infections in pregnancy is complicated by potential effects of drugs on the fetus. Peri- and postpartum maternal infection is a major cause of maternal mortality. The effects of infection in pregnancy can be broadly categorized as follows (these are not mutually exclusive): (1) transplacental infection causing fetal malformation, e.g. treponema pallidum, rubella; (2) transplacental infection causing severe in utero illness, e.g. parvovirus; (3) neonatal infection / carrier status as a result of transplacental or intrapartum infection, e.g. HIV, herpes zoster; such neonatal infection may be severe; (4) preterm delivery, late miscarriage, perinatal death and cerebral palsy at term delivery are more common in the presence of in utero and placental infection (chorioamnionitis), e.g. Group B streptococcus....


2020 ◽  
pp. 2678-2686
Author(s):  
Lawrence Impey

This chapter looks at the fetal effects of maternal infection. Immunity is mildly suppressed in pregnancy, and the fetal immune system is developmentally immature. Infections in pregnancy can therefore be devastating both for the mother, as is occasionally seen with varicella, and for the fetus, as exemplified by congenital infections such as those caused by rubella, cytomegalovirus, syphilis, and toxoplasmosis. The fetal effects of maternal infection in pregnancy can be broadly categorized as follows (these are not mutually exclusive): transplacental infection causing fetal malformation (e.g. treponema pallidum, rubella); transplacental infection causing severe in utero illness (e.g. parvovirus); neonatal infection/carrier status as a result of transplacental or intrapartum infection (e.g. HIV, herpes zoster); such neonatal infection may be severe; preterm delivery, late miscarriage, perinatal death, and cerebral palsy at term delivery are more common in the presence of in utero and placental infection (chorioamnionitis) (e.g. group B streptococcus).


2016 ◽  
Vol 16 (8) ◽  
pp. 923-934 ◽  
Author(s):  
Shabir A Madhi ◽  
Clare L Cutland ◽  
Lisa Jose ◽  
Anthonet Koen ◽  
Niresha Govender ◽  
...  

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