Cellular and Molecular Neurobiology

, Volume 38, Issue 7, pp 1349–1368 | Cite as

Mechanisms of Blood Brain Barrier Disruption by Different Types of Bacteria, and Bacterial–Host Interactions Facilitate the Bacterial Pathogen Invading the Brain

  • Mazen M. Jamil Al-ObaidiEmail author
  • Mohd Nasir Mohd DesaEmail author
Review Paper


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.


Blood brain barrier Bacterial infection Meningitis Therapeutic strategies 



This study was supported by the fundamental research grant scheme, (Grant No. 5524924), and long term research grant scheme (Grant No. 5526406), Ministry of education Malaysia.

Author Contributions

MMJ designed the manuscript, searched the literatures and wrote the review. MNMD revised the review.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. Abbott NJ, Rönnbäck L, Hansson E (2006) Astrocyte–endothelial interactions at the blood–brain barrier. Nat Rev Neurosci 7:41–53. CrossRefPubMedGoogle Scholar
  2. Abbott NJ, Patabendige AAK, Dolman DEM et al (2010) Structure and function of the blood-brain barrier. Neurobiol Dis 37:13–25. CrossRefPubMedGoogle Scholar
  3. Abe R, Oda S, Sadahiro T et al (2010) Gram-negative bacteremia induces greater magnitude of inflammatory response than Gram-positive bacteremia. Crit Care 14:R27. CrossRefPubMedPubMedCentralGoogle Scholar
  4. Aguilar J, Urday-Cornejo V, Donabedian S et al (2010) Staphylococcus aureus meningitis: case series and literature review. Medicine 89:117–125. CrossRefPubMedGoogle Scholar
  5. Antal E-A, Løberg E-M, Dietrichs E, Maehlen J (2005) Neuropathological findings in 9 cases of listeria monocytogenes brain stem encephalitis. Brain Pathol 15:187–191CrossRefPubMedGoogle Scholar
  6. Attali C, Durmort C, Vernet T, Di Guilmi AM (2008) The interaction of Streptococcus pneumoniae with plasmin mediates transmigration across endothelial and epithelial monolayers by intercellular junction cleavage. Infect Immun 76:5350–5356. CrossRefPubMedPubMedCentralGoogle Scholar
  7. Baggiolini M, Dewald B, Moser B (1993) lnterleukin-8 and related chemotactic cytokines—CXC and CC chemokines. Adv Immunol 55:97–179. CrossRefGoogle Scholar
  8. Banerjee A, van Sorge NM, Sheen TR et al (2010) Activation of brain endothelium by pneumococcal neuraminidase NanA promotes bacterial internalization. Cell Microbiol 12:1576–1588. CrossRefPubMedPubMedCentralGoogle Scholar
  9. Banerjee A, Kim BJ, Carmona EM et al (2011a) Bacterial Pili exploit integrin machinery to promote immune activation and efficient blood-brain barrier penetration. Nat Commun 2:462. CrossRefPubMedPubMedCentralGoogle Scholar
  10. Banerjee A, Kim BJ, Carmona EM et al (2011b) Bacterial Pili exploit integrin machinery to promote immune activation and efficient blood-brain barrier penetration. Nat Commun. CrossRefPubMedPubMedCentralGoogle Scholar
  11. Barichello T, dos Santos I, Savi GD et al (2010) TNF-α, IL-1β, IL-6, and cinc-1 levels in rat brain after meningitis induced by Streptococcus pneumoniae. J Neuroimmunol 221:42–45. CrossRefPubMedGoogle Scholar
  12. Barichello T, Lemos JC, Generoso JS et al (2011a) Oxidative stress, cytokine/chemokine and disruption of blood-brain barrier in neonate rats after meningitis by streptococcus agalactiae. Neurochem Res 36:1922–1930. CrossRefPubMedGoogle Scholar
  13. Barichello T, Pereira JS, Savi GD et al (2011b) A kinetic study of the cytokine/chemokines levels and disruption of blood–brain barrier in infant rats after pneumococcal meningitis. J Neuroimmunol 233:12–17. CrossRefPubMedGoogle Scholar
  14. Barichello T, Generoso JS, Collodel A et al (2012a) Pathophysiology of acute meningitis caused by Streptococcus pneumoniae and adjunctive therapy approaches. Arq Neuropsiquiatr 70:366–372. CrossRefPubMedGoogle Scholar
  15. Barichello T, Generoso JS, Silvestre C et al (2012b) Circulating concentrations, cerebral output of the CINC-1 and blood-brain barrier disruption in Wistar rats after pneumococcal meningitis induction. Eur J Clin Microbiol Infect Dis 31:2005–2009. CrossRefPubMedGoogle Scholar
  16. Baucells JB, Hally MM et al (2016) Probiotic associations in the prevention of necrotising enterocolitis and the reduction of late-onset sepsis and neonatal mortality in preterm infants under 1500 g. A systematic review. An Pediatr (Barc)JFigueras Aloy 85:247–255. CrossRefGoogle Scholar
  17. Bebbington C, Yarranton G (2008) Antibodies for the treatment of bacterial infections: current experience and future prospects. Curr Opin Biotechnol 19:613–619CrossRefPubMedGoogle Scholar
  18. Bell LM, Alpert G, Campos JM, Plotkin SA (1985) Routine quantitative blood cultures in children with Haemophilus influenzae or Streptococcus pneumoniae bacteremia. Pediatrics 76:901–904PubMedGoogle Scholar
  19. Biegel D, Spencer DD, Pachter JS (1995) Isolation and culture of human brain microvessel endothelial cells for the study of blood-brain barrier properties in vitro. Brain Res 692:183–189. CrossRefPubMedGoogle Scholar
  20. Brito MA, Palmela I, Cardoso FL et al (2014) Blood–brain barrier and bilirubin: clinical aspects and experimental data. Arch Med Res 45:660–676CrossRefPubMedGoogle Scholar
  21. Brouwer MC, Tunkel AR, Van De Beek D (2010) Epidemiology, diagnosis, and antimicrobial treatment of acute bacterial meningitis. Clin Microbiol Rev 23:467–492CrossRefPubMedPubMedCentralGoogle Scholar
  22. Carrano A, Hoozemans JJM, van der Vies SM et al (2011) Amyloid beta induces oxidative stress-mediated blood–brain barrier changes in capillary amyloid angiopathy. Antioxid Redox Signal 15:1167–1178. CrossRefPubMedGoogle Scholar
  23. Chiang Y-C, Liao W-W, Fan C-M et al (2008) PCR detection of Staphylococcal enterotoxins (SEs) N, O, P, Q, R, U, and survey of SE types in Staphylococcus aureus isolates from food-poisoning cases in Taiwan. Int J Food Microbiol 121:66–73. CrossRefPubMedGoogle Scholar
  24. Cho JS, Pietras EM, Garcia NC et al (2010) IL-17 is essential for host defense against cutaneous Staphylococcus aureus infection in mice. J Clin Invest 120:1762–1773. CrossRefPubMedPubMedCentralGoogle Scholar
  25. Chung MC, Popova TG, Jorgensen SC et al (2008) Degradation of circulating von Willebrand factor and its regulator ADAMTS13 implicates secreted Bacillus anthracis metalloproteases in anthrax consumptive coagulopathy. J Biol Chem 283:9531–9542. CrossRefPubMedGoogle Scholar
  26. Chung MC, Jorgensen SC, Popova TG et al (2009) Activation of plasminogen activator inhibitor implicates protease InhA in the acute-phase response to Bacillus anthracis infection. J Med Microbiol 58:737–744. CrossRefPubMedGoogle Scholar
  27. Coureuil M, Mikaty G, Miller F et al (2009) Meningococcal type IV pili recruit the polarity complex to cross the brain endothelium. Science 325:83–87. CrossRefPubMedGoogle Scholar
  28. Coureuil M, Lécuyer H, Scott MGH et al (2010) Meningococcus hijacks a β2-adrenoceptor/β-arrestin pathway to cross brain microvasculature endothelium. Cell 143:1149–1160. CrossRefPubMedGoogle Scholar
  29. Crone C, Olesen SP (1982) Electrical resistance of brain microvascular endothelium. Brain Res 241:49–55. CrossRefPubMedGoogle Scholar
  30. Cundell DR, Gerard NP, Gerard C et al (1995) Streptococcus pneumoniae anchor to activated human cells by the receptor for platelet-activating factor. Nature 377:435–438. CrossRefPubMedGoogle Scholar
  31. Danne C, Dramsi S (2012) Pili of Gram-positive bacteria: roles in host colonization. Res Microbiol 163:645–658. CrossRefPubMedGoogle Scholar
  32. Davoust N, Vuaillat C, Androdias G, Nataf S (2008) From bone marrow to microglia: barriers and avenues. Trends Immunol 29:227–234CrossRefPubMedGoogle Scholar
  33. De Lange ECM (2004) Potential role of ABC transporters as a detoxification system at the blood-CSF barrier. Adv Drug Deliv Rev 56:1793–1809CrossRefPubMedGoogle Scholar
  34. Dinarello CA (2005) Interleukin-1. Crit Care Med 33:S460–S462CrossRefPubMedGoogle Scholar
  35. Doran KS, Liu GY, Nizet V (2003) Group B streptococcal β-hemolysin/cytolysin activates neutrophil signaling pathways in brain endothelium and contributes to development of meningitis. J Clin Invest 112:736–744. CrossRefPubMedPubMedCentralGoogle Scholar
  36. Doran KS, Engelson EJ, Khosravi A et al (2005) Blood-brain barrier invasion by group B. Streptococcus depends upon proper cell-surface anchoring of lipoteichoic acid. J Clin Invest 115:2499–2507. CrossRefPubMedPubMedCentralGoogle Scholar
  37. Doran KS, Fulde M, Gratz N et al (2016) Host–pathogen interactions in bacterial meningitis. Acta Neuropathol 131:185–209CrossRefPubMedPubMedCentralGoogle Scholar
  38. Drevets DA, Leenen PJM, Greenfield RA (2004) Invasion of the central nervous system by intracellular bacteria. Clin Microbiol Rev 17:323–347CrossRefPubMedPubMedCentralGoogle Scholar
  39. Ebrahimi CM, Kern JW, Sheen TR et al (2009) Penetration of the blood–brain barrier by Bacillus anthracis requires the pXO1-encoded BslA protein. J Bacteriol 191:7165–7173. CrossRefPubMedPubMedCentralGoogle Scholar
  40. Ebrahimi CM, Sheen TR, Renken CW et al (2011) Contribution of lethal toxin and edema toxin to the pathogenesis of anthrax meningitis. Infect Immun 79:2510–2518. CrossRefPubMedPubMedCentralGoogle Scholar
  41. Edmond KM, Kortsalioudaki C, Scott S et al (2012) Group B streptococcal disease in infants aged younger than 3 months: systematic review and meta-analysis. Lancet 379:547–556. CrossRefPubMedGoogle Scholar
  42. Edwards MS, Baker CJ (2005) Group B streptococcal infections in elderly adults. Clin Infect Dis an Off Publ Infect Dis Soc Am 41:839–847. CrossRefGoogle Scholar
  43. Er TK, Cheng BH, Ginés MÁR (2009) Importance of cerebrospinal fluid analysis in stat laboratory. Am J Emerg Med. CrossRefPubMedGoogle Scholar
  44. Esen N, Wagoner G, Philips N (2010) Evaluation of capsular and acapsular strains of S. aureus in an experimental brain abscess model. J Neuroimmunol 218:83–93. CrossRefPubMedGoogle Scholar
  45. Ferrieri P, Burke B, Nelson J (1980) Production of bacteremia and meningitis in infant rats with group B streptococcal serotypes. Infect Immun 27:1023–1032PubMedPubMedCentralGoogle Scholar
  46. Fida NM, Al-Mughales J, Farouq M (2006) Interleukin-1alpha, interleukin-6 and tumor necrosis factor-alpha levels in children with sepsis and meningitis. Pediatr Int 48:118–124. CrossRefPubMedGoogle Scholar
  47. Foster TJ, Geoghegan JA, Ganesh VK, Höök M (2014) Adhesion, invasion and evasion: the many functions of the surface proteins of Staphylococcus aureus. NatRevMicrobiol 12:49–62. CrossRefGoogle Scholar
  48. Furuse M, Fujita K, Hiiragi T et al (1998) Claudin-1 and -2: novel integral membrane proteins localizing at tight junctions with no sequence similarity to occludin. J Cell Biol 141:1539–1550. CrossRefPubMedPubMedCentralGoogle Scholar
  49. Gouin E, Adib-Conquy M, Balestrino D et al (2010) The Listeria monocytogenes InlC protein interferes with innate immune responses by targeting the I{kappa}B kinase subunit IKK{alpha}. Proc Natl Acad Sci USA 107:17333–17338. CrossRefPubMedGoogle Scholar
  50. Gozes Y, Moayeri M, Wiggins JF, Leppla SH (2006) Anthrax lethal toxin induces ketotifen-sensitive intradermal vascular leakage in certain inbred mice. Infect Immun 74:1266–1272. CrossRefPubMedPubMedCentralGoogle Scholar
  51. Gray SJ, Trotter CL, Ramsay ME et al (2006) Epidemiology of meningococcal disease in England and Wales 1993/94 to 2003/04: contribution and experiences of the meningococcal reference unit. J Med Microbiol 55:887–896. CrossRefPubMedGoogle Scholar
  52. Greiffenberg L, Goebel W, Kim KS et al (1998) Interaction of Listeria monocytogenes with human brain microvascular endothelial cells: InlB-dependent invasion, long-term intracellular growth, and spread from macrophages to endothelial cells. Infect Immun 66:5260–5267PubMedPubMedCentralGoogle Scholar
  53. Greiffenberg L, Goebel W, Kim KS et al (2000) Interaction of Listeria monocytogenes with human brain microvascular endothelial cells: an electron microscopic study. Infect Immun 68:3275–3279. CrossRefPubMedPubMedCentralGoogle Scholar
  54. Gründler T, Quednau N, Stump C et al (2013) The surface proteins InlA and InlB are interdependently required for polar basolateral invasion by Listeria monocytogenes in a human model of the blood-cerebrospinal fluid barrier. Microbes Infect 15:291–301. CrossRefPubMedGoogle Scholar
  55. Gruol DL, Nelson TE (1997) Physiological and pathological roles of interleukin-6 in the central nervous system. Mol Neurobiol 15:307–339. CrossRefPubMedPubMedCentralGoogle Scholar
  56. Guillemet E, Cadot C, Tran SL et al (2010) The InhA metalloproteases of Bacillus cereus contribute concomitantly to virulence. J Bacteriol 192:286–294. CrossRefPubMedGoogle Scholar
  57. Hawkins BT, Davis TP (2005) The blood–brain barrier/neurovascular unit in health and disease. Pharmacol Rev 57:173–185. CrossRefPubMedGoogle Scholar
  58. Heninger M, Collins KA (2013) Acute bacterial meningitis with coincident methamphetamine use: a case report and review of the literature. J Forensic Sci 58:1088–1091. CrossRefPubMedGoogle Scholar
  59. Hirst RA, Kadioglu A, O’Callaghan C, Andrew PW (2004) The role of pneumolysin in pneumococcal pneumonia and meningitis. Clin Exp Immunol 138:195–201CrossRefPubMedPubMedCentralGoogle Scholar
  60. Howard M, O’Garra A (1992) Biological properties of interleukin 10. Immunol Today 13:198–200. CrossRefPubMedGoogle Scholar
  61. Huang W-H, Hung P-K (2006) Methicillin-resistant Staphylococcus aureus infections in acute rhinosinusitis. Laryngoscope 116:288–291. CrossRefPubMedGoogle Scholar
  62. Huang SH, Wass C, Fu Q et al (1995) Escherichia coli invasion of brain microvascular endothelial cells in vitro and in vivo: molecular cloning and characterization of invasion gene ibe10. Infect Immun 63:4470–4475PubMedPubMedCentralGoogle Scholar
  63. Hudault S, Guignot J, Servin AL (2001) Escherichia coli strains colonising the gastrointestinal tract protect germfree mice against Salmonella typhimurium infection. Gut 49:47–55. CrossRefPubMedPubMedCentralGoogle Scholar
  64. Ichiyama T, Isumi H, Yoshitomi T et al (2002) NF-kappaB activation in cerebrospinal fluid cells from patients with meningitis. Neurol Res 24:709–712. CrossRefPubMedGoogle Scholar
  65. Inglesby TV, O’Toole T, Henderson D et al (2002) Anthrax as a biological weapon, 2002. JAMA 287:2236. CrossRefPubMedPubMedCentralGoogle Scholar
  66. Iovino F, Brouwer MC, van de Beek D et al (2013a) Signalling or binding: the role of the platelet-activating factor receptor in invasive pneumococcal disease. Cell Microbiol 15:870–881CrossRefPubMedGoogle Scholar
  67. Iovino F, Orihuela CJ, Moorlag HE et al (2013b) Interactions between blood-borne Streptococcus pneumoniae and the blood–brain barrier preceding meningitis. PLoS ONE. CrossRefPubMedPubMedCentralGoogle Scholar
  68. Iovino F, Molema G, Bijlsma JJE (2014) Platelet endothelial cell adhesion molecule-1, a putative receptor for the adhesion of Streptococcus pneumoniae to the vascular endothelium of the blood-brain barrier. Infect Immun 82:3555–3566. CrossRefPubMedPubMedCentralGoogle Scholar
  69. Iovino F, Seinen J, Henriques-Normark B, van Dijl JM (2016) How does Streptococcus pneumoniae invade the brain? Trends Microbiol 24:307–315. CrossRefPubMedGoogle Scholar
  70. Iovino F, Engelen-Lee J-Y, Brouwer M et al (2017) pIgR and PECAM-1 bind to pneumococcal adhesins RrgA and PspC mediating bacterial brain invasion. J Exp Med 214:1619–1630. CrossRefPubMedPubMedCentralGoogle Scholar
  71. Janoff EN, Fasching C, Orenstein JM et al (1999) Killing of Streptococcus pneumoniae by capsular polysaccharide-specific polymeric IgA, complement, and phagocytes. J Clin Invest 104:1139–1147. CrossRefPubMedPubMedCentralGoogle Scholar
  72. Join-Lambert O, Morand PC, Carbonnelle E et al (2010) Mechanisms of meningeal invasion by a bacterial extracellular pathogen, the example of Neisseria meningitidis. Prog Neurobiol 91:130–139CrossRefPubMedGoogle Scholar
  73. Kastrup CJ, Boedicker JQ, Pomerantsev AP et al (2008) Spatial localization of bacteria controls coagulation of human blood by “quorum acting”. Nat Chem Biol 4:742–750. CrossRefPubMedPubMedCentralGoogle Scholar
  74. Kayal S, Charbit A (2006) Listeriolysin O: a key protein of Listeria monocytogenes with multiple functions. FEMS Microbiol Rev 30:514–529CrossRefPubMedGoogle Scholar
  75. Kayal S, Lilienbaum A, Join-Lambert O et al (2002) Listeriolysin O secreted by Listeria monocytogenes induces NF-kappaB signalling by activating the IkappaB kinase complex. Mol Microbiol 44:1407–1419CrossRefPubMedGoogle Scholar
  76. Kebir H, Kreymborg K, Ifergan I et al (2007) Human TH17 lymphocytes promote blood–brain barrier disruption and central nervous system inflammation. Nat Med 13:1173–1175. CrossRefPubMedPubMedCentralGoogle Scholar
  77. Kenneth JR, Ray CG (2004) Sherris Medical MicrobiologyGoogle Scholar
  78. Kern J, Schneewind O (2010) BslA, the S-layer adhesin of B. anthracis, is a virulence factor for anthrax pathogenesis. Mol Microbiol 75:324–332. CrossRefPubMedGoogle Scholar
  79. Khan NA, Wang Y, Kim KJ et al (2002) Cytotoxic necrotizing factor-1 contributes to Escherichia coli K1 invasion of the central nervous system. J Biol Chem 277:15607–15612. CrossRefPubMedGoogle Scholar
  80. Kielian T, Hickey WF (2000) Proinflammatory cytokine, chemokine, and cellular adhesion molecule expression during the acute phase of experimental brain abscess development. Am J Pathol 157:647–658. CrossRefPubMedPubMedCentralGoogle Scholar
  81. Kim KS (2003) Pathogenesis of bacterial meningitis: from bacteraemia to neuronal injury. Nat Rev Neurosci 4:376. CrossRefPubMedGoogle Scholar
  82. Kim KS (2008) Mechanisms of microbial traversal of the blood–brain barrier. Nat Rev Microbiol 6:625–634. CrossRefPubMedPubMedCentralGoogle Scholar
  83. Kim KJ, Chung JW, Kim KS (2005) 67-kDa laminin receptor promotes internalization of cytotoxic necrotizing factor 1-expressing Escherichia coli K1 into human brain microvascular endothelial cells. J Biol Chem 280:1360–1368. CrossRefPubMedGoogle Scholar
  84. Kniesel U, Wolburg H (2000) Tight junctions of the blood-brain barrier. Cell Mol Neurobiol 20:57–76. CrossRefPubMedPubMedCentralGoogle Scholar
  85. Koedel U, Bernatowicz A, Frei K et al (1996) Systemically (but not intrathecally) administered IL-10 attenuates pathophysiologic alterations in experimental pneumococcal meningitis. J Immunol 157:5185–5191PubMedGoogle Scholar
  86. Koedel U, Scheld WM, Pfister HW (2002) Pathogenesis and pathophysiology of pneumococcal meningitis. Lancet Infect Dis 2:721–736CrossRefPubMedGoogle Scholar
  87. Kolberg J, Høiby EA, Jantzen E (1997) Detection of the phosphorylcholine epitope in streptococci, Haemophilus and pathogenic Neisseriae by immunoblotting. Microb Pathog 22:321–329. CrossRefPubMedGoogle Scholar
  88. Konsman JP, Drukarch B, Van Dam A-M (2007) (Peri)vascular production and action of pro-inflammatory cytokines in brain pathology. Clin Sci 112:1–25. CrossRefPubMedGoogle Scholar
  89. Kornelisse RF, Savelkoul HF, Mulder PH et al (1996) Interleukin-10 and soluble tumor necrosis factor receptors in cerebrospinal fluid of children with bacterial meningitis. J Infect Dis 173:1498–1502CrossRefPubMedGoogle Scholar
  90. Kronfol Z (2000) Cytokines and the brain: implications for clinical psychiatry. Am J Psychiatry 157:683–694. CrossRefPubMedGoogle Scholar
  91. Kyaw MH, Christie P, Jones IG, Campbell H (2002) The changing epidemiology of bacterial meningitis and invasive non-meningitic bacterial disease in Scotland during the period 1983–1999. Scand J Infect Dis 34:289–298. CrossRefPubMedGoogle Scholar
  92. Leclercq SY, Sullivan MJ, Ipe DS et al (2016) Pathogenesis of Streptococcus urinary tract infection depends on bacterial strain and β-hemolysin/cytolysin that mediates cytotoxicity, cytokine synthesis, inflammation and virulence. Sci Rep. CrossRefPubMedPubMedCentralGoogle Scholar
  93. Lehner MD, Schwoebel F, Kotlyarov A et al (2002) Mitogen-activated protein kinase-activated protein kinase 2-deficient mice show increased susceptibility to Listeria monocytogenes infection. J Immunol 168:4667–4673CrossRefPubMedGoogle Scholar
  94. Leib SL, Kim YS, Black SM et al (1998) Inducible nitric oxide synthase and the effect of aminoguanidine in experimental neonatal meningitis. J Infect Dis 177:692–700CrossRefPubMedGoogle Scholar
  95. Lembo A, Gurney MA, Burnside K et al (2010) Regulation of CovR expression in Group B Streptococcus impacts blood-brain barrier penetration. Mol Microbiol 77:431–443. CrossRefPubMedPubMedCentralGoogle Scholar
  96. Levin VA (1980) Relationship of octanol/water partition coefficient and molecular weight to rat brain capillary permeability. J Med Chem 23:682–684. CrossRefPubMedGoogle Scholar
  97. Maisey HC, Hensler M, Nizet V, Doran KS (2007) Group B streptococcal pilus proteins contribute to adherence to and invasion of brain microvascular endothelial cells. In: Journal of Bacteriology. pp 1464–1467Google Scholar
  98. Manarey CRA, Anand VK, Huang C (2004) Incidence of methicillin-resistant staphylococcus aureus causing chronic rhinosinusitis. Laryngoscope 114:939–941CrossRefPubMedGoogle Scholar
  99. Marriott H, Mitchell T, Dockrell D (2008) Pneumolysin: a double-edged sword during the host–pathogen interaction. Curr Mol Med 8:497–509. CrossRefPubMedGoogle Scholar
  100. Martìn-Padura I, Lostaglio S, Schneemann M et al (1998) Junctional adhesion molecule, a novel member of the immunoglobulin superfamily that distributes at intercellular junctions and modulates monocyte transmigration. J Cell Biol 142:117–127. CrossRefPubMedPubMedCentralGoogle Scholar
  101. Mayhan WG (2000) Nitric oxide donor-induced increase in permeability of the blood-brain barrier. Brain Res 866:101–108. CrossRefPubMedGoogle Scholar
  102. McLoughlin A, Rochfort KD, McDonnell CJ et al (2017) Staphylococcus aureus-mediated blood–brain barrier injury: an in vitro human brain microvascular endothelial cell model. Cell Microbiol. CrossRefPubMedGoogle Scholar
  103. Melican K, Dumenil G (2012) Vascular colonization by Neisseria meningitidis. Curr Opin Microbiol 15:50–56CrossRefPubMedGoogle Scholar
  104. Miller SD, McMahon EJ, Schreiner B, Bailey SL (2007) Antigen presentation in the CNS by myeloid dendritic cells drives progression of relapsing experimental autoimmune encephalomyelitis. Ann NY Acad Sci 1103:179–191CrossRefPubMedGoogle Scholar
  105. Miric D, Katanic R, Kisic B et al (2010) Oxidative stress and myeloperoxidase activity during bacterial meningitis: effects of febrile episodes and the BBB permeability. Clin Biochem 43:246–252. CrossRefPubMedGoogle Scholar
  106. Mittal R, Prasadarao NV (2010) Nitric oxide/cGMP signalling induces Escherichia coli K1 receptor expression and modulates the permeability in human brain endothelial cell monolayers during invasion. Cell Microbiol 12:67–83. CrossRefPubMedGoogle Scholar
  107. Møller K, Tofteng F, Qvist T et al (2005) Cerebral output of cytokines in patients with pneumococcal meningitis. Crit Care Med 33:979–983. CrossRefPubMedGoogle Scholar
  108. Moreillon P, Majcherczyk PA (2003) Proinflammatory activity of cell-wall constituents from Gram-positive bacteria. Scand J Infect Dis 35:632–641. CrossRefPubMedGoogle Scholar
  109. Moura RP, Almeida A, Sarmento B (2017) The role of non-endothelial cells on the penetration of nanoparticles through the blood–brain barrier. Prog Neurobiol 159:39–49. CrossRefPubMedGoogle Scholar
  110. Mukherjee DV, Tonry JH, Kim KS et al (2011) Bacillus anthracis protease InhA increases blood–brain barrier permeability and contributes to cerebral hemorrhages. PLoS ONE. CrossRefPubMedPubMedCentralGoogle Scholar
  111. Murawska-Cialowicz E, Szychowska Z, Tr busiewicz B (2000) Nitric oxide production during bacterial and viral meningitis in children. Int J Clin Lab Res 30:127–131CrossRefPubMedGoogle Scholar
  112. Nagesh Babu G, Kumar A, Kalita J, Misra UK (2008) Proinflammatory cytokine levels in the serum and cerebrospinal fluid of tuberculous meningitis patients. Neurosci Lett 436:48–51. CrossRefPubMedGoogle Scholar
  113. Nandi A, Dey S, Biswas J et al (2015) Differential induction of inflammatory cytokines and reactive oxygen species in murine peritoneal macrophages and resident fresh bone marrow cells by acute Staphylococcus aureus infection: contribution of toll-like receptor 2 (TLR2). Inflammation 38:224–244. CrossRefPubMedGoogle Scholar
  114. Nasdala I, Wolburg-Buchholz K, Wolburg H et al (2002) A transmembrane tight junction protein selectively expressed on endothelial cells and platelets. J Biol Chem 277:16294–16303. CrossRefPubMedGoogle Scholar
  115. Nizet V, Kim KS, Stins M et al (1997) Invasion of brain microvascular endothelial cells by group B streptococci. Infect Immun 65:5074–5081PubMedPubMedCentralGoogle Scholar
  116. Opitz B, Püschel A, Beermann W et al (2006) Listeria monocytogenes activated p38 MAPK and induced IL-8 secretion in a nucleotide-binding oligomerization domain 1-dependent manner in endothelial cells. J Immunol 176:484–490. CrossRefPubMedGoogle Scholar
  117. Orihuela CJ, Mahdavi J, Thornton J et al (2009) Laminin receptor initiates bacterial contact with the blood brain barrier in experimental meningitis models. J Clin Invest 119:1638–1646. CrossRefPubMedPubMedCentralGoogle Scholar
  118. Østergaard C, Brandt C, Konradsen HB, Samuelsson S (2004) Differences in survival, brain damage, and cerebrospinal fluid cytokine kinetics due to meningitis caused by 3 different Streptococcus pneumoniae serotypes: evaluation in humans and in 2 experimental models. J Infect Dis 190:1212–1220. CrossRefPubMedGoogle Scholar
  119. Parida SK, Domann E, Ronde M et al (1998) Internalin B is essential for adhesion and mediates the invasion of Listera monocytognes into human endothelial cells. Mol Microbiol 28:81–93. CrossRefPubMedGoogle Scholar
  120. Parizzi F, Garlaschi L, Assael BM et al (1991) Interleukin 6 activity in infants and children with bacterial meningitis. the collaborative study on meningitis. Pediatr Infect Dis J 10:117–121CrossRefPubMedGoogle Scholar
  121. Park WB, Kim S-H, Cho JH et al (2007) Effect of salicylic acid on invasion of human vascular endothelial cells by Staphylococcus aureus. FEMS Immunol Med Microbiol 49:56–61CrossRefPubMedGoogle Scholar
  122. Patrick D, Betts J, Frey EA et al (1992) Haemophilus influenzae lipopolysaccharide disrupts confluent monolayers of bovine brain endothelial cells via a serum-dependent cytotoxic pathway. J Infect Dis 165:865–872. CrossRefPubMedGoogle Scholar
  123. Paul R, Koedel U, Winkler F et al (2003) Lack of IL-6 augments inflammatory response but decreases vascular permeability in bacterial meningitis. Brain 126:1873–1882. CrossRefPubMedGoogle Scholar
  124. Peltola H (2000) Worldwide Haemophilus influenzae type b disease at the beginning of the 21st century: global analysis of the disease burden 25 years after the use of the polysaccharide vaccine and a decade after the advent of conjugates. Clin Microbiol Rev 13:302–317CrossRefPubMedPubMedCentralGoogle Scholar
  125. Prasadarao NV (2002) Identification of Escherichia coli outer membrane protein A receptor on human brain microvascular endothelial cells. InfectImmun 70:4556–4563. CrossRefGoogle Scholar
  126. Prasadarao NV, Blom AM, Villoutreix BO, Linsangan LC (2002) A novel interaction of outer membrane protein A with C4b binding protein mediates serum resistance of Escherichia coli K1. J Immunol 169:6352–6360. CrossRefPubMedGoogle Scholar
  127. Privratsky JR, Newman PJ (2014) PECAM-1: regulator of endothelial junctional integrity. Cell Tissue Res 355:607–619CrossRefPubMedPubMedCentralGoogle Scholar
  128. Quagliarello VJ, Long WJ, Scheld WM (1986) Morphologic alterations of the blood–brain barrier with experimental meningitis in the rat. Temporal sequence and role of encapsulation. J Clin Invest 77:1084–1095. CrossRefPubMedPubMedCentralGoogle Scholar
  129. Quagliarello VJ, Wispelwey B, Long WJ, Scheld WM (1991) Recombinant human interleukin-1 induces meningitis and blood-brain barrier injury in the rat: characterization and comparison with tumor necrosis factor. J Clin Invest 87:1360–1366. CrossRefPubMedPubMedCentralGoogle Scholar
  130. Radin JN, Orihuela CJ, Murti G et al (2005) β-arrestin 1 participates in platelet-activating factor receptor-mediated endocytosis of Streptococcus pneumoniae. Infect Immun 73:7827–7835. CrossRefPubMedPubMedCentralGoogle Scholar
  131. Ramarao N, Lereclus D (2005) The InhA 1 metalloprotease allows spores of the B. cereus group to escape macrophages. Cell Microbiol 7:1357–1364. CrossRefPubMedGoogle Scholar
  132. Ring A, Weiser JN, Tuomanen EI (1998) Pneumococcal trafficking across the blood–brain barrier molecular analysis of a novel bidirectional pathway. J Clin Invest 102:347–360. CrossRefPubMedPubMedCentralGoogle Scholar
  133. Rochfort KD, Cummins PM (2015) Cytokine-mediated dysregulation of zonula occludens-1 properties in human brain microvascular endothelium. Microvasc Res 100:48–53. CrossRefPubMedGoogle Scholar
  134. Rochfort KD, Collins LE, McLoughlin A, Cummins PM (2016) Tumour necrosis factor-α-mediated disruption of cerebrovascular endothelial barrier integrity in vitro involves the production of proinflammatory interleukin-6. J Neurochem 136:564–572. CrossRefPubMedGoogle Scholar
  135. Rosa-Fraile M, Dramsi S, Spellerberg B (2014) Group B streptococcal haemolysin and pigment, a tale of twins. FEMS Microbiol Rev 38:932–946. CrossRefPubMedPubMedCentralGoogle Scholar
  136. Rosenberg GA, Estrada EY, Dencoff JE, Stetler-Stevenson WG (1995) Tumor necrosis factor-α-induced gelatinase B causes delayed opening of the blood–brain barrier: an expanded therapeutic window. Brain Res 703:151–155. CrossRefPubMedGoogle Scholar
  137. Saez-Llorens X, Jafari HS, Severien C et al (1991) Enhanced attenuation of meningeal inflammation and brain edema by concomitant administration of anti-CD18 monoclonal antibodies and dexamethasone in experimental Haemophilus meningitis. J Clin Invest 88:2003–2011. CrossRefPubMedPubMedCentralGoogle Scholar
  138. Schmeck B, Beermann W, van Laak V et al (2005) Intracellular bacteria differentially regulated endothelial cytokine release by MAPK-dependent histone modification. J Immunol 175:2843–2850CrossRefPubMedGoogle Scholar
  139. Schubert-Unkmeir A, Konrad C, Slanina H et al (2010) Neisseria meningitidis induces brain microvascular endothelial cell detachment from the matrix and cleavage of occludin: a role for MMP-8. PLoS Pathog 6:e1000874. CrossRefPubMedPubMedCentralGoogle Scholar
  140. Schuchat a, Robinson K, Wenger JD et al (1997) Bacterial meningitis in the United States in 1995. Active surveillance team. N Engl J Med 337:970–976. CrossRefPubMedGoogle Scholar
  141. Sellner J, Täuber MG, Leib SL (2010) Pathogenesis and pathophysiology of bacterial CNS infections. Handb Clin Neurol 96:1–16. CrossRefPubMedGoogle Scholar
  142. Seo HS, Mu R, Kim BJ et al (2012) Binding of glycoprotein Srr1 of Streptococcus agalactiae to fibrinogen promotes attachment to brain endothelium and the development of meningitis. PLoS Pathog. CrossRefPubMedPubMedCentralGoogle Scholar
  143. Sheen TR, Ebrahimi CM, Hiemstra IH et al (2010) Penetration of the blood–brain barrier by Staphylococcus aureus: contribution of membrane-anchored lipoteichoic acid. J Mol Med 88:633–639. CrossRefPubMedPubMedCentralGoogle Scholar
  144. Sokolova O, Heppel N, Jägerhuber R et al (2004) Interaction of Neisseria meningitidis with human brain microvascular endothelial cells: Role of MAP- and tyrosine kinases in invasion and inflammatory cytokine release. Cell Microbiol 6:1153–1166. CrossRefPubMedGoogle Scholar
  145. St Geme 3rd JW, Cutter D (1996) Influence of pili, fibrils, and capsule on in vitro adherence by Haemophilus influenzae type b. Mol Microbiol 21:21–31CrossRefPubMedGoogle Scholar
  146. St. Geme JW, Cutter D (1995) Evidence that surface fibrils expressed by Haemophilus influenzae type b promote attachment to human epithelial cells. Mol Microbiol 15:77–85CrossRefGoogle Scholar
  147. Stephens DS (1999) Uncloaking the meningococcus: dynamics of carriage and disease. Lancet 353:941CrossRefPubMedGoogle Scholar
  148. Stephens DS (2007) Conquering the meningococcus. FEMS Microbiol Rev 31:3–14CrossRefPubMedGoogle Scholar
  149. Sukumaran SK, Prasadarao NV (2003) Escherichia coli K1 invasion increases human brain microvascular endothelial cell monolayer permeability by disassembling vascular-endothelial cadherins at tight junctions. J Infect Dis 188:1295–1309. CrossRefPubMedGoogle Scholar
  150. Swords WE, Ketterer MR, Shao J et al (2001) Binding of the non-typeable Haemophilus influenzae lipooligosaccharide to the PAF receptor initiates host cell signalling. Cell Microbiol 3:525–536. CrossRefPubMedGoogle Scholar
  151. Tang P, Rosenshine I, Finlay BB (1994) Listeria monocytogenes, an invasive bacterium, stimulates MAP kinase upon attachment to epithelial cells. Mol Biol Cell 5:455–464CrossRefPubMedPubMedCentralGoogle Scholar
  152. Tang P, Sutherland CL, Gold MR, Finlay BB (1998) Listeria monocytogenes invasion of epithelial cells requires the MEK-1/ERK-2 mitogen-activated protein kinase pathway. Infect Immun 66:1106–1112PubMedPubMedCentralGoogle Scholar
  153. Tazi A, Disson O, Bellais S et al (2010) The surface protein HvgA mediates group B streptococcus hypervirulence and meningeal tropism in neonates. J Exp Med 207:2313–2322. CrossRefPubMedPubMedCentralGoogle Scholar
  154. Tenaillon O, Skurnik D, Picard B, Denamur E (2010) The population genetics of commensal Escherichia coli. NatRevMicrobiol 8:207–217. CrossRefGoogle Scholar
  155. Teng CH, Cai M, Shin S et al (2005) Escherichia coli K1 RS218 interacts with human brain microvascular endothelial cells via type 1 fimbria bacteria in the fimbriated state. Infect Immun 73:2923–2931. CrossRefPubMedPubMedCentralGoogle Scholar
  156. Tsukita S, Furuse M, Itoh M (2001) Multifunctional strands in tight junctions. Nat Rev Mol Cell Biol 2:285–293. CrossRefPubMedGoogle Scholar
  157. Tuomanen EI, Saukkonen K, Sande S et al (1989) Reduction of inflammation, tissue damage, and mortality in bacterial meningitis in rabbits treated with monoclonal antibodies against adhesion-promoting receptors of leukocytes. J Exp Med 170:959–969CrossRefPubMedGoogle Scholar
  158. Uchiyama S, Carlin AF, Khosravi A et al (2009) The surface-anchored NanA protein promotes pneumococcal brain endothelial cell invasion. J Exp Med 206:1845–1852. CrossRefPubMedPubMedCentralGoogle Scholar
  159. van Sorge NM, Doran KS (2012) Defense at the border: the blood–brain barrier versus bacterial foreigners. Future Microbiol 7:383–394. CrossRefPubMedPubMedCentralGoogle Scholar
  160. van Sorge NM, Ebrahimi CM, McGillivray SM et al (2008) Anthrax toxins inhibit neutrophil signaling pathways in brain endothelium and contribute to the pathogenesis of meningitis. PLoS ONE. CrossRefPubMedPubMedCentralGoogle Scholar
  161. van Sorge NM, Quach D, Gurney M et al (2009) The group B streptococcal serine-rich repeat 1 glycoprotein mediates penetration of the blood–brain barrier. J Infect Dis 199:1479–1487. CrossRefPubMedPubMedCentralGoogle Scholar
  162. van de Beek D, de Gans J, Tunkel AR, Wijdicks EFM (2006) Community-acquired Bacterial meningitis in adults. N Engl J Med 354:44–53. CrossRefPubMedGoogle Scholar
  163. van der Poll T, Keogh CV, Guirao X et al (1997) Interleukin-6 gene-deficient mice show impaired defense against Pneumococcal pneumonia. J Infect Dis 176:439–444. CrossRefPubMedGoogle Scholar
  164. Vázquez-Boland JA, Kuhn M, Berche P et al (2001) Listeria pathogenesis and molecular virulence determinants. Clin Microbiol Rev 14:584–640CrossRefPubMedPubMedCentralGoogle Scholar
  165. Virji M (2009) Pathogenic neisseriae: surface modulation, pathogenesis and infection control. Nat Rev Microbiol 7:274–286CrossRefPubMedGoogle Scholar
  166. Vogt RL, Dippold L (2005) Escherichia coli O157:H7 outbreak associated with consumption of ground beef, June–July 2002. Public Health Rep 120:174–178. CrossRefPubMedPubMedCentralGoogle Scholar
  167. Wang J, Sun L, Si YF, Li BM (2012) Overexpression of actin-depolymerizing factor blocks oxidized low-density lipoprotein-induced mouse brain microvascular endothelial cell barrier dysfunction. Mol Cell Biochem 371:1–8. CrossRefPubMedGoogle Scholar
  168. Warfel JM, Steele AD, D’Agnillo F (2005) Anthrax lethal toxin induces endothelial barrier dysfunction. Am J Pathol 166:1871–1881. CrossRefPubMedPubMedCentralGoogle Scholar
  169. Watt JP, Wolfson LJ, O’Brien KL et al (2009) Burden of disease caused by Haemophilus influenzae type b in children younger than 5 years: global estimates. Lancet 374:903–911. CrossRefPubMedGoogle Scholar
  170. Weiser JN, Pan N, McGowan KL et al (1998) Phosphorylcholine on the lipopolysaccharide of Haemophilus influenzae contributes to persistence in the respiratory tract and sensitivity to serum killing mediated by C-reactive protein. J Exp Med 187:631–640. CrossRefPubMedPubMedCentralGoogle Scholar
  171. Weiss N, Miller F, Cazaubon S, Couraud PO (2009) The blood–brain barrier in brain homeostasis and neurological diseases. Biochim Biophys Acta 1788:842–857CrossRefPubMedGoogle Scholar
  172. Wellmer A, Zysk G, Gerber J et al (2002) Decreased virulence of a pneumolysin-deficient strain of Streptococcus pneumoniae in murine meningitis. Infect Immun 70:6504–6508. CrossRefPubMedPubMedCentralGoogle Scholar
  173. Whidbey C, Harrell MI, Burnside K et al (2013) A hemolytic pigment of Group B Streptococcus allows bacterial penetration of human placenta. J Exp Med 210:1265–1281. CrossRefPubMedPubMedCentralGoogle Scholar
  174. Whidbey C, Vornhagen J, Gendrin C et al (2015) A streptococcal lipid toxin induces membrane permeabilization and pyroptosis leading to fetal injury. EMBO Mol Med 7:488–505. CrossRefPubMedPubMedCentralGoogle Scholar
  175. Winkler F, Koedel U, Kastenbauer S, Pfister H-W (2001) Differential expression of nitric oxide synthases in bacterial meningitis: role of the inducible isoform for blood–brain barrier breakdown. J Infect Dis 183:1749–1759. CrossRefPubMedGoogle Scholar
  176. Wolburg H, Lippoldt A (2002) Tight junctions of the blood–brain barrier: development, composition and regulation. Vascul Pharmacol 38:323–337CrossRefPubMedGoogle Scholar
  177. Wolburg H, Wolburg-Buchholz K, Engelhardt B (2005) Diapedesis of mononuclear cells across cerebral venules during experimental autoimmune encephalomyelitis leaves tight junctions intact. Acta Neuropathol 109:181–190. CrossRefPubMedGoogle Scholar
  178. Yadav A, Malik GK, Trivedi R et al (2009) Correlation of CSF neuroinflammatory molecules with leptomeningeal cortical subcortical white matter fractional anisotropy in neonatal meningitis. Magn Reson Imaging 27:214–221. CrossRefPubMedGoogle Scholar
  179. Zhang JR, Mostov KE, Lamm ME et al (2000) The polymeric immunoglobulin receptor translocates pneumococci across human nasopharyngeal epithelial cells. Cell 102:827–837. CrossRefPubMedGoogle Scholar
  180. Zhou Y, Tao J, Yu H et al (2012) Hcp family proteins secreted via the type VI secretion system coordinately regulate Escherichia coli K1 interaction with human brain microvascular endothelial cells. Infect Immun 80:1243–1251. CrossRefPubMedPubMedCentralGoogle Scholar
  181. Zwijnenburg PJG, Van der Poll T, Florquin S et al (2003) Interleukin-10 negatively regulates local cytokine and chemokine production but does not influence antibacterial host defense during murine Pneumococcal meningitis. Infect Immun 71:2276–2279. CrossRefPubMedPubMedCentralGoogle Scholar
  182. Zysk G, Schneider-Wald BK, Hwang JH et al (2001) Pneumolysin is the main inducer of cytotoxicity to brain microvascular endothelial cells caused by Streptococcus pneumoniae. Infect Immun 69:845–852. CrossRefPubMedPubMedCentralGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Biomedical Science, Faculty of Medicine and Health SciencesUniversiti Putra MalaysiaSerdangMalaysia
  2. 2.Halal Products Research InstituteUniversiti Putra MalaysiaSerdangMalaysia

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