@article{KimMcDonaghDengetal.2019,
  author    = {Kim, Brandon J. and McDonagh, Maura A. and Deng, Liwen and Gastfriend, Benjamin D. and Schubert-Unkmeir, Alexandra and Doran, Kelly S. and Shusta, Eric V.},
  title     = {Streptococcus agalactiae disrupts P-glycoprotein function in brain endothelial cells},
  series = {Fluids and Barriers of the CNS},
  volume    = {16},
  journal   = {Fluids and Barriers of the CNS},
  doi       = {10.1186/s12987-019-0146-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201895},
  pages     = {26},
  year      = {2019},
  abstract  = {Bacterial meningitis is a serious life threatening infection of the CNS. To cause meningitis, blood-borne bacteria need to interact with and penetrate brain endothelial cells (BECs) that comprise the blood-brain barrier. BECs help maintain brain homeostasis and they possess an array of efflux transporters, such as P-glycoprotein (P-gp), that function to efflux potentially harmful compounds from the CNS back into the circulation. Oftentimes, efflux also serves to limit the brain uptake of therapeutic drugs, representing a major hurdle for CNS drug delivery. During meningitis, BEC barrier integrity is compromised; however, little is known about efflux transport perturbations during infection. Thus, understanding the impact of bacterial infection on P-gp function would be important for potential routes of therapeutic intervention. To this end, the meningeal bacterial pathogen, Streptococcus agalactiae, was found to inhibit P-gp activity in human induced pluripotent stem cell-derived BECs, and live bacteria were required for the observed inhibition. This observation was correlated to decreased P-gp expression both in vitro and during infection in vivo using a mouse model of bacterial meningitis. Given the impact of bacterial interactions on P-gp function, it will be important to incorporate these findings into analyses of drug delivery paradigms for bacterial infections of the CNS.},
  language  = {en}
}