Hyaluronidase Impairs Neutrophil Function and Promotes Group B<i>Streptococcus</i>Invasion and Preterm Labor in Nonhuman Primates
Michelle M. Coleman, Blair Armistead, Austyn Orvis, Phoenicia Quach, Alyssa Brokaw, Claire Gendrin, Kavita Sharma, Jason Ogle, Sean Merillat, Matthew Dacanay, Tsung-Yen Wu, Jeff Munson, Audrey Baldessari, Jay Vornhagen, Anna Furuta, Shayla Nguyen, Kristina M. Adams Waldorf, Lakshmi Rajagopal
Abstract
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.