Morbidity and mortality of preterm and newborn infants remain significant public health concerns. Streptococcus agalactiae or Group B Streptococcus (GBS) are a leading cause of bacterial infection associated preterm births, stillbirths and early onset sepsis. We recently showed that increased expression of the hyaluronidase can be associated with GBS invasive disease and induces fetal demise in pregnant mice. The objective of this proposal is to understand how the GBS hyaluronidase subverts the function of multiple host innate immune cells to induce fetal injury and systemic infection.
Aim 1 will define mechanisms by which the GBS hyaluronidase subverts immune cell function and immune cell recruitment.
Aim 2 will establish how expression of the GBS hyaluronidase promotes microbial invasion of the amniotic cavity and fetal injury in the pregnant nonhuman primate model that closely emulates human pregnancy. These studies will provide novel insight into mechanisms of immune evasion during GBS infections. These results are essential and invaluable for development of novel therapeutic approaches to reduce the risk of GBS infection associated fetal injury, stillbirth, preterm births and neonatal infections.
Understanding how pathogen encoded hyaluronidase affects immune cell function and recruitment will be invaluable for the development of therapeutic strategies to prevent Group B Streptococcal infections that include preterm births, stillbirths, and neonatal disease.
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