<p class="first" id="d103279e79">This review aims to elucidate the different mechanisms
of blood brain barrier (BBB)
disruption that may occur due to invasion by different types of bacteria, as well
as to show the bacteria-host interactions that assist the bacterial pathogen in invading
the brain. For example, platelet-activating factor receptor (PAFR) is responsible
for brain invasion during the adhesion of pneumococci to brain endothelial cells,
which might lead to brain invasion. Additionally, the major adhesin of the pneumococcal
pilus-1, RrgA is able to bind the BBB endothelial receptors: polymeric immunoglobulin
receptor (pIgR) and platelet endothelial cell adhesion molecule (PECAM-1), thus leading
to invasion of the brain. Moreover, Streptococcus pneumoniae choline binding protein
A (CbpA) targets the common carboxy-terminal domain of the laminin receptor (LR) establishing
initial contact with brain endothelium that might result in BBB invasion. Furthermore,
BBB disruption may occur by S. pneumoniae penetration through increasing in pro-inflammatory
markers and endothelial permeability. In contrast, adhesion, invasion, and translocation
through or between endothelial cells can be done by S. pneumoniae without any disruption
to the vascular endothelium, upon BBB penetration. Internalins (InlA and InlB) of
Listeria monocytogenes interact with its cellular receptors E-cadherin and mesenchymal-epithelial
transition (MET) to facilitate invading the brain. L. monocytogenes species activate
NF-κB in endothelial cells, encouraging the expression of P- and E-selectin, intercellular
adhesion molecule 1 (ICAM-1), and Vascular cell adhesion protein 1 (VCAM-1), as well
as IL-6 and IL-8 and monocyte chemoattractant protein-1 (MCP-1), all these markers
assist in BBB disruption. Bacillus anthracis species interrupt both adherens junctions
(AJs) and tight junctions (TJs), leading to BBB disruption. Brain microvascular endothelial
cells (BMECs) permeability and BBB disruption are induced via interendothelial junction
proteins reduction as well as up-regulation of IL-1α, IL-1β, IL-6, TNF-α, MCP-1, macrophage
inflammatory proteins-1 alpha (MIP1α) markers in Staphylococcus aureus species. Streptococcus
agalactiae or Group B Streptococcus toxins (GBS) enhance IL-8 and ICAM-1 as well as
nitric oxide (NO) production from endothelial cells via the expression of inducible
nitric oxide synthase (iNOS) enhancement, resulting in BBB disruption. While Gram-negative
bacteria, Haemophilus influenza OmpP2 is able to target the common carboxy-terminal
domain of LR to start initial interaction with brain endothelium, then invade the
brain. H. influenza type b (HiB), can induce BBB permeability through TJ disruption.
LR and PAFR binding sites have been recognized as common routes of CNS entrance by
Neisseria meningitidis. N. meningitidis species also initiate binding to BMECs and
induces AJs deformation, as well as inducing specific cleavage of the TJ component
occludin through the release of host MMP-8. Escherichia coli bind to BMECs through
LR, resulting in IL-6 and IL-8 release and iNOS production, as well as resulting in
disassembly of TJs between endothelial cells, facilitating BBB disruption. Therefore,
obtaining knowledge of BBB disruption by different types of bacterial species will
provide a picture of how the bacteria enter the central nervous system (CNS) which
might support the discovery of therapeutic strategies for each bacteria to control
and manage infection.
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