Bacterial Hyaluronidase Promotes Ascending GBS Infection and Preterm Birth

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....

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Autores principales:	Jay Vornhagen, Phoenicia Quach, Erica Boldenow, Sean Merillat, Christopher Whidbey, Lisa Y. Ngo, K. M. Adams Waldorf, Lakshmi Rajagopal
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2016
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/2bbb36e28c3041e9bf43e3ec8fa037d1
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spelling	oai:doaj.org-article:2bbb36e28c3041e9bf43e3ec8fa037d12021-11-15T15:50:16ZBacterial Hyaluronidase Promotes Ascending GBS Infection and Preterm Birth10.1128/mBio.00781-162150-7511https://doaj.org/article/2bbb36e28c3041e9bf43e3ec8fa037d12016-07-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00781-16https://doaj.org/toc/2150-7511ABSTRACT 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.Jay VornhagenPhoenicia QuachErica BoldenowSean MerillatChristopher WhidbeyLisa Y. NgoK. M. Adams WaldorfLakshmi RajagopalAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 7, Iss 3 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Jay Vornhagen Phoenicia Quach Erica Boldenow Sean Merillat Christopher Whidbey Lisa Y. Ngo K. M. Adams Waldorf Lakshmi Rajagopal Bacterial Hyaluronidase Promotes Ascending GBS Infection and Preterm Birth
description	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.
format	article
author	Jay Vornhagen Phoenicia Quach Erica Boldenow Sean Merillat Christopher Whidbey Lisa Y. Ngo K. M. Adams Waldorf Lakshmi Rajagopal
author_facet	Jay Vornhagen Phoenicia Quach Erica Boldenow Sean Merillat Christopher Whidbey Lisa Y. Ngo K. M. Adams Waldorf Lakshmi Rajagopal
author_sort	Jay Vornhagen
title	Bacterial Hyaluronidase Promotes Ascending GBS Infection and Preterm Birth
title_short	Bacterial Hyaluronidase Promotes Ascending GBS Infection and Preterm Birth
title_full	Bacterial Hyaluronidase Promotes Ascending GBS Infection and Preterm Birth
title_fullStr	Bacterial Hyaluronidase Promotes Ascending GBS Infection and Preterm Birth
title_full_unstemmed	Bacterial Hyaluronidase Promotes Ascending GBS Infection and Preterm Birth
title_sort	bacterial hyaluronidase promotes ascending gbs infection and preterm birth
publisher	American Society for Microbiology
publishDate	2016
url	https://doaj.org/article/2bbb36e28c3041e9bf43e3ec8fa037d1
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Bacterial Hyaluronidase Promotes Ascending GBS Infection and Preterm Birth

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