A study led by Seattle Children’s Research Institute and published today in EMBO Molecular Medicine, titled “A Streptococcal Lipid Toxin Induces Membrane Permeabilization and Pyroptosis Leading to Fetal Injury,” reveals new information on the common bacteria Group B Streptococcus (GBS). Researchers hope these discoveries could one day be used to prevent premature births and stillbirths.
A global problem
Preterm birth and early onset infections lead to approximately 1.4 million neonatal deaths worldwide each year. In the United States, 30% of infants born are premature. In developing countries, the problem is much more severe. Nonetheless, there is no effective therapy to prevent preterm birth and stillbirth, in part because of the lack of information on factors contributing to in utero infections.
GBS is a type of bacteria commonly found in healthy women. It typically does not cause infections in women, but can cause infections to neonates in utero, leading to fetal injury and resulting in preterm birth or stillbirth. GBS can also infect newborns during birth, later causing pneumonia, sepsis and meningitis.
Currently, pregnant women in the United States are tested for GBS during pregnancy. If the bacteria are present, mothers are given IV antibiotics during labor to prevent the newborn from being infected during birth. Still, there is no effective therapy to prevent infections in utero.
Searching for answers
To prevent GBS infections in utero, Dr. Lakshmi Rajagopal, an investigator in the Center for Global Infectious Disease Research at Seattle Children’s Research Institute, is trying to better understand GBS and how infections occur before birth.
Rajagopal’s previous GBS research, published in the Journal of Experimental Medicine in 2013, determined the hemolytic toxin found in GBS was not a protein, as previous believed, but a different cell component known as a lipid. With a better understanding of this toxin, Rajagopal and colleagues began to investigate how the toxin contributes to fetal injury.
Her latest study reveals which mechanisms used by the GBS toxin lead to fetal injury. If future interventions prevent these mechanisms, preterm births and stillbirths related to GBS could potentially be prevented.
“We utilized many different methods and people with a wide range of expertise from biophysics, microbiology, molecular biology, cell biology, immunology and gynecology contributed to this study to address these outstanding questions,” Rajagopal said.
This study, funded by the National Institutes of Health, determined how a toxin produced by the GBS bacteria causes cell death and triggers inflammation – both causes of fetal injury in utero. The toxin pokes holes in cells, leading to different types of cell death in different cells.
“Our next step will be to see how we can mitigate GBS induced fetal injury,” Rajagopal said. “We will conduct further research to identity potential interventions that could stop these mechanisms and decrease or prevent in utero infections.”