Tight Junction Proteins and Bacterial Pathogens Impacting the Brain

ABSTRACT The blood–brain barrier (BBB) is an essential protective structure that preserves the homeostasis of the central nervous system (CNS) by controlling the transfer of chemicals and infections from the bloodstream into the tissues of the brain. The BBB is primarily composed of brain microvascular endothelial cells (BMECs), which are closely linked by tight junction (TJ) proteins, including occludin, claudins and junctional adhesion molecules (JAMs). However, certain bacterial infections, such as those caused by Escherichia coli ( E. coli ), Neisseria meningitidis ( N. meningitidis ), Streptococcus pneumoniae ( S. pneumoniae ) and Haemophilus influenzae ( H. influenzae ), have developed strategies to compromise these TJs, facilitating their invasion of the CNS and resulting in meningitis. These bacteria utilise several virulence factors, including outer membrane proteins, pili and toxins, to modify host cell signalling pathways, compromise the BBB and facilitate their translocation across barriers. This study aims to clarify the molecular processes employed by these pathogens to penetrate the BBB, with an emphasis on their effects on TJ integrity. A comprehension of these mechanisms is essential for formulating effective medicines to prevent and cure bacterial meningitis by safeguarding or restoring BBB integrity.