Table 1 Virulence-related factors involved in BBB disruption

AtlA_SS

Autolysin protein

Adhesin Modulating chain length

BMECs, FN, FG

[17]

SadP

Streptococcal adhesin P

Adhesin

Gb3, Gb4

[19]

SsPepO

Fibronectin binding protein

Adhesin Increasing the permeability of BBB Immune evasion

BMECs, FN, PG

[23, 24]

SssP1

Fimbria-like protein

Adhesin

Promoting the capacity of invasion

Promoting cytokine expression

BMECs, Vimentin, Sialic acids

[25, 26]

DltA

Lipoteichoic acid (LTA) D-alanylation

Promoting the capacity of adherence and invasion

BMECs

[27]

NadR

Nicotinamide-nucleotide adenylyltransferase

Promoting the capacity of adherence and invasion

BMECs

[30]

PrsA

Peptidyl-prolyl isomerase

Cytotoxicity

Affecting secretion or translocation of virulence factors

Immune evasion

bEnd.3

[31, 32]

rss04

Small RNA

Promoting the capacity of adherence and invasion

Regulating transcription and virulence factors expression

Regulating biofilm formation

Promoting cytokine expression

bEnd.3, CcpA

[34]

SrtA

Sortase A

Promoting the capacity of adherence and invasion

Protein sorting and anchoring

BMECs

[37,38,39]

STK/STP

Serine-threonine kinase/phosphatase

Phosphorylation and Dephosphorylation

Promoting the capacity of adherence and invasion

Affecting secretion or translocation of virulence factors

Modulating chain length and surface structures

Involving in cell division

Inducing disruption of the JPs

Affecting the expression of E3 ubiquitin ligase

BMECs, bEnd.3, GlmM, DivIVA

[43,44,45,46, 48, 86]

VraSR

Two-component signal transduction system

Promoting bacterial adherence

Increasing the permeability of BBB

Downregulating the expression of JPs

Regulating the CPS biosynthesis

Immune evasion

BMECs, bEnd.3

[49,50,51]

Fhb

Factor H binding protein

Promoting the capacity of adherence and invasion

Immune evasion

BMECs, Gb3, FH

[53, 87]

MRP

Muraminidase released protein

Promoting the capacity of adherence and invasion

Increasing the permeability of BBB

Destroying the stability of p120-Catenin

Immune evasion

BMECs, bEnd.3, FN, FG, FH, IgG

[56, 58,59,60]

Phospholipase C

Hydrolyzing phosphatidylcholine

Inducing the release of arachidonic acid

BMECs

[61]

Ssads

Adenosine synthase

Adenosine production

Increasing the permeability of BBB

Inducing cytoskeletal reorganization and JPs redistribution

Immune evasion

BMECs, A1 AR, A2A AR

[62, 63]

Hyl

Hyaluronidase

Increasing the permeability of BBB

AI1

[66]

Eno

Enolase

Promoting bacterial adherence

Increasing the permeability of BBB

Promoting cytokine expression

Inducing cell apoptosis

BMECs, FN, PG, RPSA

[67,68,69,70,71, 88]

SspA

Serine-associated subtilisin-like protease

Cytotoxicity

Promoting cytokine expression

BMECs

[73,74,75]

Suilysin

Hemolysin

Cytotoxicity

Increasing the permeability of BBB

Inducing intravascular thrombosis

Inducing cytoskeletal reorganization

Promoting cytokine expression and degradationInducing cell apoptosis

BMECs, Platelet, Astrocytes, Rac1, RhoA

[76,77,78,79,80,81]

PgdA

Peptidoglycan N-acetylglucosamine deacetylase

Unknown

BMECs, Peptidoglycan

[82, 83]

AdcA, Lmb

Zn-binding lipoproteins

Promoting the capacity of adherence and invasion

BMECs

[84]