Streptococcus agalactiae disrupts P-glycoprotein function in brain endothelial cells.

Area of Science:

• Neuroscience
• Infectious Diseases
• Pharmacology

Background:

• Bacterial meningitis is a life-threatening central nervous system (CNS) infection.
• Brain endothelial cells (BECs) form the blood-brain barrier, regulating CNS homeostasis and drug transport.
• P-glycoprotein (P-gp) efflux transporters in BECs limit drug entry into the CNS.

Purpose of the Study:

• To investigate the impact of bacterial infection on P-gp function in BECs.
• To understand how Streptococcus agalactiae affects P-gp activity and expression during meningitis.
• To assess implications for CNS drug delivery during bacterial meningitis.

Main Methods:

• Utilized human induced pluripotent stem cell-derived BECs.
• Exposed BECs to Streptococcus agalactiae in vitro.
• Assessed P-gp activity and expression.
• Validated findings in a mouse model of bacterial meningitis in vivo.

Main Results:

• Streptococcus agalactiae significantly inhibited P-gp activity in BECs.
• Live bacteria were essential for the observed P-gp inhibition.
• P-gp expression was decreased both in vitro and during in vivo infection.
• Bacterial meningitis alters efflux transporter function.

Conclusions:

• Bacterial meningitis disrupts P-gp function in the blood-brain barrier.
• Streptococcus agalactiae actively downregulates P-gp expression and activity.
• Findings highlight the need to consider infection-induced changes in P-gp for CNS drug delivery strategies.