Host–pathogen interactions in bacterial meningitis

Al-Numani D, Segura M, Dore M, Gottschalk M (2003) Up-regulation of ICAM-1, CD11a/CD18 and CD11c/CD18 on human THP-1 monocytes stimulated by Streptococcus suis serotype 2. Clin Exp Immunol 133:67–77 Alkuwaity K, Taylor A, Heckels JE, Doran KS, Christodoulides M (2012) Group B Streptococcus interactions with human meningeal cells and astrocytes in vitro. PLoS One 7:e42660. doi:10.1371/journal.pone.0042660 Baker CJ, Edwards MS (2001) Group B streptococcal infections. In: Remington JS, Klein JO (eds) Infectious diseases of the fetus and newborn infant, 5th edn. WB Saunders, Philadelphia, pp 1091–1156 Banerjee A, Kim BJ, Carmona EM, Cutting AS, Gurney MA, Carlos C, Feuer R, Prasadarao NV, Doran KS (2011) Bacterial Pili exploit integrin machinery to promote immune activation and efficient blood-brain barrier penetration. Nat Commun 2:462. doi:10.1038/ncomms1474 Barichello T, Collodel A, Generoso JS, Simoes LR, Moreira AP, Ceretta RA, Petronilho F, Quevedo J (2015) Targets for adjunctive therapy in pneumococcal meningitis. J Neuroimmunol 278:262–270. doi:10.1016/j.jneuroim.2014.11.015 Baums CG, Valentin-Weigand P (2009) Surface-associated and secreted factors of Streptococcus suis in epidemiology, pathogenesis and vaccine development. Anim Health Res Rev/Conf Res Work Anim Dis 10:65–83. doi:10.1017/S146625230999003X Benga L, Friedl P, Valentin-Weigand P (2005) Adherence of Streptococcus suis to porcine endothelial cells. J Vet Med B Infect Dis Vet Public Health 52:392–395. doi:10.1111/j.1439-0450.2005.00880.x Benga L, Goethe R, Rohde M, Valentin-Weigand P (2004) Non-encapsulated strains reveal novel insights in invasion and survival of Streptococcus suis in epithelial cells. Cell Microbiol 6:867–881. doi:10.1111/j.1462-5822.2004.00409.x Bergmann S, Lang A, Rohde M, Agarwal V, Rennemeier C, Grashoff C, Preissner KT, Hammerschmidt S (2009) Integrin-linked kinase is required for vitronectin-mediated internalization of Streptococcus pneumoniae by host cells. J Cell Sci 122:256–267. doi:10.1242/jcs.035600 Berman PH, Banker BQ (1966) Neonatal meningitis—a clinical and pathological study of 29 cases. Pediatrics 38:6–24 Bernard SC, Simpson N, Join-Lambert O, Federici C, Laran-Chich MP, Maissa N, Bouzinba-Segard H, Morand PC, Chretien F, Taouji S, Chevet E, Janel S, Lafont F, Coureuil M, Segura A, Niedergang F, Marullo S, Couraud PO, Nassif X, Bourdoulous S (2014) Pathogenic Neisseria meningitidis utilizes CD147 for vascular colonization. Nat Med 20:725–731. doi:10.1038/nm.3563 Bradley CJ, Griffiths NJ, Rowe HA, Heyderman RS, Virji M (2005) Critical determinants of the interactions of capsule-expressing Neisseria meningitidis with host cells: the role of receptor density in increased cellular targeting via the outer membrane Opa proteins. Cell Microbiol 7:1490–1503. doi:10.1111/j.1462-5822.2005.00572.x Brandt CT, Lundgren JD, Lund SP, Frimodt-Moller N, Christensen T, Benfield T, Espersen F, Hougaard DM, Ostergaard C (2004) Attenuation of the bacterial load in blood by pretreatment with granulocyte-colony-stimulating factor protects rats from fatal outcome and brain damage during Streptococcus pneumoniae meningitis. Infect Immun 72:4647–4653. doi:10.1128/IAI.72.8.4647-4653.2004 Braun JS, Novak R, Herzog KH, Bodner SM, Cleveland JL, Tuomanen EI (1999) Neuroprotection by a caspase inhibitor in acute bacterial meningitis. Nat Med 5:298–302. doi:10.1038/6514 Chang YC, Wang Z, Flax LA, Xu D, Esko JD, Nizet V, Baron MJ (2011) Glycosaminoglycan binding facilitates entry of a bacterial pathogen into central nervous systems. PLoS Pathog 7:e1002082. doi:10.1371/journal.ppat.1002082 Charland N, Nizet V, Rubens CE, Kim KS, Lacouture S, Gottschalk M (2000) Streptococcus suis serotype 2 interactions with human brain microvascular endothelial cells. Infect Immun 68:637–643 Coureuil M, Lecuyer H, Scott MG, Boularan C, Enslen H, Soyer M, Mikaty G, Bourdoulous S, Nassif X, Marullo S (2010) Meningococcus Hijacks a beta2-adrenoceptor/beta-Arrestin pathway to cross brain microvasculature endothelium. Cell 143:1149–1160. doi:10.1016/j.cell.2010.11.035 Coureuil M, Mikaty G, Miller F, Lecuyer H, Bernard C, Bourdoulous S, Dumenil G, Mege RM, Weksler BB, Romero IA, Couraud PO, Nassif X (2009) Meningococcal type IV pili recruit the polarity complex to cross the brain endothelium. Science 325:83–87. doi:10.1126/science.1173196 Coutinho LG, Grandgirard D, Leib SL, Agnez-Lima LF (2013) Cerebrospinal-fluid cytokine and chemokine profile in patients with pneumococcal and meningococcal meningitis. BMC Infect Dis 13:326. doi:10.1186/1471-2334-13-326 Cumley NJ, Smith LM, Anthony M, May RC (2012) The CovS/CovR acid response regulator is required for intracellular survival of group B Streptococcus in macrophages. Infect Immun 80:1650–1661. doi:10.1128/IAI.05443-11 Cundell DR, Gerard NP, Gerard C, Idanpaan-Heikkila I, Tuomanen EI (1995) Streptococcus pneumoniae anchor to activated human cells by the receptor for platelet-activating factor. Nature 377:435–438. doi:10.1038/377435a0 Cundell DR, Weiser JN, Shen J, Young A, Tuomanen EI (1995) Relationship between colonial morphology and adherence of Streptococcus pneumoniae. Infect Immun 63:757–761 Cutting AS, Del Rosario Y, Mu R, Rodriguez A, Till A, Subramani S, Gottlieb RA, Doran KS (2014) The role of autophagy during group B Streptococcus infection of blood-brain barrier endothelium. J Biol Chem 289:35711–35723. doi:10.1074/jbc.M114.588657 Dacey RG, Sande MA (1974) Effect of probenecid on cerebrospinal fluid concentrations of penicillin and cephalosporin derivatives. Antimicrob Agents Chemother 6:437–441 de Buhr N, Neumann A, Jerjomiceva N, von Kockritz-Blickwede M, Baums CG (2014) Streptococcus suis DNase SsnA contributes to degradation of neutrophil extracellular traps (NETs) and evasion of NET-mediated antimicrobial activity. Microbiology 160:385–395. doi:10.1099/mic.0.072199-0 de Buhr N, Stehr M, Neumann A, Naim HY, Valentin-Weigand P, von Kockritz-Blickwede M, Baums CG (2015) Identification of a novel DNase of Streptococcus suis (EndAsuis) important for neutrophil extracellular trap degradation during exponential growth. Microbiology 161:838–850. doi:10.1099/mic.0.000040 Dominguez-Punaro MC, Segura M, Plante MM, Lacouture S, Rivest S, Gottschalk M (2007) Streptococcus suis serotype 2, an important swine and human pathogen, induces strong systemic and cerebral inflammatory responses in a mouse model of infection. J Immunol 179:1842–1854 Dominguez-Punaro Mde L, Segura M, Contreras I, Lachance C, Houde M, Lecours MP, Olivier M, Gottschalk M (2010) In vitro characterization of the microglial inflammatory response to Streptococcus suis, an important emerging zoonotic agent of meningitis. Infect Immun 78:5074–5085. doi:10.1128/IAI.00698-10 Doran KS, Engelson EJ, Khosravi A, Maisey HC, Fedtke I, Equils O, Michelsen KS, Arditi M, Peschel A, Nizet V (2005) Blood-brain barrier invasion by group B Streptococcus depends upon proper cell-surface anchoring of lipoteichoic acid. J Clin Investig 115:2499–2507. doi:10.1172/JCI23829 Doran KS, Liu GY, Nizet V (2003) Group B streptococcal beta-hemolysin/cytolysin activates neutrophil signaling pathways in brain endothelium and contributes to development of meningitis. J Clin Investig 112:736–744. doi:10.1172/JCI17335 Edmond KM, Kortsalioudaki C, Scott S, Schrag SJ, Zaidi AK, Cousens S, Heath PT (2012) Group B streptococcal disease in infants aged younger than 3 months: systematic review and meta-analysis. Lancet 379:547–556. doi:10.1016/S0140-6736(11)61651-6 Edwards MS, Rench MA, Haffar AA, Murphy MA, Desmond MM, Baker CJ (1985) Long-term sequelae of group B streptococcal meningitis in infants. J Pediatr 106:717–722 Eugene E, Hoffmann I, Pujol C, Couraud PO, Bourdoulous S, Nassif X (2002) Microvilli-like structures are associated with the internalization of virulent capsulated Neisseria meningitidis into vascular endothelial cells. J Cell Sci 115:1231–1241 Fagan RP, Lambert MA, Smith SG (2008) The hek outer membrane protein of Escherichia coli strain RS218 binds to proteoglycan and utilizes a single extracellular loop for adherence, invasion, and autoaggregation. Infect Immun 76:1135–1142. doi:10.1128/IAI.01327-07 Ferrando ML, Fuentes S, de Greeff A, Smith H, Wells JM (2010) ApuA, a multifunctional alpha-glucan-degrading enzyme of Streptococcus suis, mediates adhesion to porcine epithelium and mucus. Microbiology 156:2818–2828. doi:10.1099/mic.0.037960-0 Fillon S, Soulis K, Rajasekaran S, Benedict-Hamilton H, Radin JN, Orihuela CJ, El Kasmi KC, Murti G, Kaushal D, Gaber MW, Weber JR, Murray PJ, Tuomanen EI (2006) Platelet-activating factor receptor and innate immunity: uptake of gram-positive bacterial cell wall into host cells and cell-specific pathophysiology. J Immunol 177:6182–6191 Fittipaldi N, Segura M, Grenier D, Gottschalk M (2012) Virulence factors involved in the pathogenesis of the infection caused by the swine pathogen and zoonotic agent Streptococcus suis. Future Microbiol 7:259–279. doi:10.2217/fmb.11.149 Fittipaldi N, Sekizaki T, Takamatsu D, de la Cruz Dominguez-Punaro M, Harel J, Bui NK, Vollmer W, Gottschalk M (2008) Significant contribution of the pgdA gene to the virulence of Streptococcus suis. Mol Microbiol 70:1120–1135. doi:10.1111/j.1365-2958.2008.06463.x Fittipaldi N, Sekizaki T, Takamatsu D, Harel J, Dominguez-Punaro Mde L, Von Aulock S, Draing C, Marois C, Kobisch M, Gottschalk M (2008) D-Alanylation of lipoteichoic acid contributes to the virulence of Streptococcus suis. Infect Immun 76:3587–3594. doi:10.1128/IAI.01568-07 Fulde M, Willenborg J, de Greeff A, Benga L, Smith HE, Valentin-Weigand P, Goethe R (2011) ArgR is an essential local transcriptional regulator of the arcABC operon in Streptococcus suis and is crucial for biological fitness in an acidic environment. Microbiology 157:572–582. doi:10.1099/mic.0.043067-0 Furyk JS, Swann O, Molyneux E (2011) Systematic review: neonatal meningitis in the developing world. Trop Med Int Health TM IH 16:672–679. doi:10.1111/j.1365-3156.2011.02750.x Gottschalk M, Xu J, Calzas C, Segura M (2010) Streptococcus suis: a new emerging or an old neglected zoonotic pathogen? Future Microbiol 5:371–391. doi:10.2217/fmb.10.2 Gould JM, Weiser JN (2002) The inhibitory effect of C-reactive protein on bacterial phosphorylcholine platelet-activating factor receptor-mediated adherence is blocked by surfactant. J Infect Dis 186:361–371. doi:10.1086/341658 Grassme H, Becker KA (2013) Bacterial infections and ceramide. Handbook of experimental pharmacology. Springer-Verlag, Heidelberg, Germany, pp 305–320. doi:10.1007/978-3-7091-1511-4_15 Hoegen T, Tremel N, Klein M, Angele B, Wagner H, Kirschning C, Pfister HW, Fontana A, Hammerschmidt S, Koedel U (2011) The NLRP3 inflammasome contributes to brain injury in pneumococcal meningitis and is activated through ATP-dependent lysosomal cathepsin B release. J Immunol 187:5440–5451. doi:10.4049/jimmunol.1100790 Humphries HE, Triantafilou M, Makepeace BL, Heckels JE, Triantafilou K, Christodoulides M (2005) Activation of human meningeal cells is modulated by lipopolysaccharide (LPS) and non-LPS components of Neisseria meningitidis and is independent of Toll-like receptor (TLR)4 and TLR2 signalling. Cell Microbiol 7:415–430. doi:10.1111/j.1462-5822.2004.00471.x Iovino F, Molema G, Bijlsma JJ (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. doi:10.1128/IAI.00046-14 Iovino F, Orihuela CJ, Moorlag HE, Molema G, Bijlsma JJE (2013) Interactions between blood-borne Streptococcus pneumoniae and the blood-brain barrier preceding meningitis. PloS One 8(7):e68408. doi:10.1371/journal.pone.0068408 (ARTN e68408) Jen FE, Warren MJ, Schulz BL, Power PM, Swords WE, Weiser JN, Apicella MA, Edwards JL, Jennings MP (2013) Dual pili post-translational modifications synergize to mediate meningococcal adherence to platelet activating factor receptor on human airway cells. PLoS Pathog 9:e1003377. doi:10.1371/journal.ppat.1003377 Jones N, Bohnsack JF, Takahashi S, Oliver KA, Chan MS, Kunst F, Glaser P, Rusniok C, Crook DW, Harding RM, Bisharat N, Spratt BG (2003) Multilocus sequence typing system for group B streptococcus. J Clin Microbiol 41:2530–2536 Källström H, Liszewski MK, Atkinson JP, Jonsson AB (1997) Membrane cofactor protein (MCP or CD46) is a cellular pilus receptor for pathogenic Neisseria. Mol Microbiol 25:639–647. doi:10.1046/j.1365-2958.1997.4841857.x Kim BJ, Hancock BM, Bermudez A, Del Cid N, Reyes E, van Sorge NM, Lauth X, Smurthwaite CA, Hilton BJ, Stotland A, Banerjee A, Buchanan J, Wolkowicz R, Traver D, Doran KS (2015) Bacterial induction of Snail1 contributes to blood-brain barrier disruption. J Clin Investig 125:2473–2483. doi:10.1172/JCI74159 Kim KS (2003) Pathogenesis of bacterial meningitis: from bacteraemia to neuronal injury. Nat Rev Neurosci 4:376–385. doi:10.1038/nrn1103 Kim KS, Itabashi H, Gemski P, Sadoff J, Warren RL, Cross AS (1992) The K1-capsule is the critical determinant in the development of Escherichia-coli meningitis in the rat. J Clin Investig 90:897–905. doi:10.1172/Jci115965 Klein M, Paul R, Angele B, Popp B, Pfister HW, Koedel U (2006) Protein expression pattern in experimental pneumococcal meningitis. Microbes Infect/Inst Pasteur 8:974–983. doi:10.1016/j.micinf.2005.10.013 Koedel U, Bernatowicz A, Paul R, Frei K, Fontana A, Pfister HW (1995) Experimental pneumococcal meningitis: cerebrovascular alterations, brain edema, and meningeal inflammation are linked to the production of nitric oxide. Ann Neurol 37:313–323. doi:10.1002/ana.410370307 Koedel U, Frankenberg T, Kirschnek S, Obermaier B, Hacker H, Paul R, Hacker G (2009) Apoptosis is essential for neutrophil functional shutdown and determines tissue damage in experimental pneumococcal meningitis. PLoS Pathog 5(5):e1000461. doi:10.1371/journal.ppat.1000461 (ARTN e1000461) Koppe U, Suttorp N, Opitz B (2012) Recognition of Streptococcus pneumoniae by the innate immune system. Cell Microbiol 14:460–466. doi:10.1111/j.1462-5822.2011.01746.x Kostyukova NN, Volkova MO, Ivanova VV, Kvetnaya AS (1995) A study of pathogenic factors of Streptococcus pneumoniae strains causing meningitis. FEMS Immunol Med Microbiol 10:133–137 Krishnan S, Chen S, Turcatel G, Arditi M, Prasadarao NV (2013) Regulation of Toll-like receptor 2 interaction with Ecgp96 controls Escherichia coli K1 invasion of brain endothelial cells. Cell Microbiol 15:63–81. doi:10.1111/cmi.12026 Krishnan S, Liu F, Abrol R, Hodges J, Goddard WA, Prasadarao NV (2014) The interaction of N-glycans in Fc gamma Receptor I alpha-chain with Escherichia coli K1 outer membrane protein A for entry into macrophages experimental and computational analysis. J Biol Chem 289:30937–30949. doi:10.1074/jbc.M114.599407 Krishnan S, Prasadarao NV (2012) Outer membrane protein A and OprF: versatile roles in Gram-negative bacterial infections. FEBS J 279:919–931. doi:10.1111/j.1742-4658.2012.08482.x Krishnan S, Prasadarao NV (2014) Identification of minimum carbohydrate moiety in N-glycosylation sites of brain endothelial cell glycoprotein 96 for interaction with Escherichia coli K1 outer membrane protein A. Microbes Infect/Inst Pasteur 16:540–552. doi:10.1016/j.micinf.2014.06.002 Krishnan S, Shanmuganathan MV, Behenna D, Stoltz BM, Prasadarao NV (2014) Angiotensin II receptor type 1—a novel target for preventing neonatal meningitis in mice by Escherichia coli K1. J Infect Dis 209:409–419. doi:10.1093/infdis/jit499 Lauer P, Rinaudo CD, Soriani M, Margarit I, Maione D, Rosini R, Taddei AR, Mora M, Rappuoli R, Grandi G, Telford JL (2005) Genome analysis reveals pili in Group B Streptococcus. Science 309:105. doi:10.1126/science.1111563 Leib SL, Heimgartner C, Bifrare YD, Loeffler JM, Taauber MG (2003) Dexamethasone aggravates hippocampal apoptosis and learning deficiency in pneumococcal meningitis in infant rats. Pediatr Res 54:353–357. doi:10.1203/01.PDR.0000079185.67878.72 Leib SL, Leppert D, Clements J, Tauber MG (2000) Matrix metalloproteinases contribute to brain damage in experimental pneumococcal meningitis. Infect Immun 68:615–620 Liu GY, Doran KS, Lawrence T, Turkson N, Puliti M, Tissi L, Nizet V (2004) Sword and shield: linked group B streptococcal beta-hemolysin/cytolysin and carotenoid pigment function to subvert host phagocyte defense. Proc Natl Acad Sci USA 101:14491–14496. doi:10.1073/pnas.0406143101 Liu X, Chauhan VS, Young AB, Marriott I (2010) NOD2 mediates inflammatory responses of primary murine glia to Streptococcus pneumoniae. Glia 58:839–847. doi:10.1002/glia.20968 Lun S, Perez-Casal J, Connor W, Willson PJ (2003) Role of suilysin in pathogenesis of Streptococcus suis capsular serotype 2. Microb Pathog 34:27–37 Mahdi LK, Wang H, Van der Hoek MB, Paton JC, Ogunniyi AD (2012) Identification of a novel pneumococcal vaccine antigen preferentially expressed during meningitis in mice. J Clin Investig 122:2208–2220. doi:10.1172/JCI45850 Mairey E, Genovesio A, Donnadieu E, Bernard C, Jaubert F, Pinard E, Seylaz J, Olivo-Marin JC, Nassif X, Dumenil G (2006) Cerebral microcirculation shear stress levels determine Neisseria meningitidis attachment sites along the blood-brain barrier. J Exp Med 203:1939–1950. doi:10.1084/jem.20060482 Maisey HC, Doran KS, Nizet V (2008) Recent advances in understanding the molecular basis of group B Streptococcus virulence. Expert Rev Mol Med 10:e27. doi:10.1017/S1462399408000811 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. J Bacteriol 189:1464–1467. doi:10.1128/JB.01153-06 Mann B, Thornton J, Heath R, Wade KR, Tweten RK, Gao G, El Kasmi K, Jordan JB, Mitrea DM, Kriwacki R, Maisonneuve J, Alderson M, Tuomanen EI (2014) Broadly protective protein-based pneumococcal vaccine composed of pneumolysin toxoid-CbpA peptide recombinant fusion protein. J Infect Dis 209:1116–1125. doi:10.1093/infdis/jit502 Maruvada R, Argon Y, Prasadarao NV (2008) Escherichia coli interaction with human brain microvascular endothelial cells induces signal transducer and activator of transcription 3 association with the C-terminal domain of Ec-gp96, the outer membrane protein A receptor for invasion. Cell Microbiol 10:2326–2338. doi:10.1111/j.1462-5822.2008.01214.x Meng F, Wu NH, Nerlich A, Herrler G, Valentin-Weigand P, Seitz M (2015) Dynamic virus-bacterium interactions in a porcine precision-cut lung slice coinfection model: swine influenza virus paves the way for streptococcus suis infection in a two-step process. Infect Immun 83:2806–2815. doi:10.1128/IAI.00171-15 Mitchell L, Smith SH, Braun JS, Herzog KH, Weber JR, Tuomanen EI (2004) Dual phases of apoptosis in pneumococcal meningitis. J Infect Dis 190:2039–2046. doi:10.1086/425520 Mittal R, Gonzalez-Gomez I, Goth KA, Prasadarao NV (2010) Inhibition of inducible nitric oxide controls pathogen load and brain damage by enhancing phagocytosis of Escherichia coli K1 in neonatal meningitis. Am J Pathol 176:1292–1305. doi:10.2353/ajpath.2010.090851 Mittal R, Gonzalez-Gomez I, Panigrahy A, Goth K, Bonnet R, Prasadarao NV (2010) IL-10 administration reduces PGE-2 levels and promotes CR3-mediated clearance of Escherichia coli K1 by phagocytes in meningitis. J Exp Med 207:1307–1319. doi:10.1084/jem.20092265 Mittal R, Prasadarao NV (2011) gp96 expression in neutrophils is critical for the onset of Escherichia coli K1 (RS218) meningitis. Nature Commun 2:552. doi:10.1038/Ncomms1554 (Artn 552) Mook-Kanamori BB, Geldhoff M, van der Poll T, van de Beek D (2011) Pathogenesis and pathophysiology of pneumococcal meningitis. Clin Microbiol Rev 24:557–591. doi:10.1128/CMR.00008-11 Moxon ER, Ostrow PT (1977) Haemophilus influenzae meningitis in infant rats: role of bacteremia in pathogenesis of age-dependent inflammatory responses in cerebrospinal fluid. J Infect Dis 135:303–307 Mu R, Kim BJ, Paco C, Del Rosario Y, Courtney HS, Doran KS (2014) Identification of a group B streptococcal fibronectin binding protein, SfbA, that contributes to invasion of brain endothelium and development of meningitis. Infect Immun 82:2276–2286. doi:10.1128/IAI.01559-13 Nassif X, Bourdoulous S, Eugene E, Couraud PO (2002) How do extracellular pathogens cross the blood-brain barrier? Trends Microbiol 10:227–232. doi:10.1016/S0966-842x(02)02349-1 Nau R, Bruck W (2002) Neuronal injury in bacterial meningitis: mechanisms and implications for therapy. Trends Neurosci 25:38–45 Nau R, Gerber J, Bunkowski S, Bruck W (2004) Axonal injury, a neglected cause of CNS damage in bacterial meningitis. Neurology 62:509–511 Nau R, Soto A, Bruck W (1999) Apoptosis of neurons in the dentate gyrus in humans suffering from bacterial meningitis. J Neuropathol Exp Neurol 58:265–274 Nealon TJ, Mattingly SJ (1983) Association of elevated levels of cellular lipoteichoic acids of group B streptococci with human neonatal disease. Infect Immun 39:1243–1251 Nizet V, Kim KS, Stins M, Jonas M, Chi EY, Nguyen D, Rubens CE (1997) Invasion of brain microvascular endothelial cells by group B streptococci. Infect Immun 65:5074–5081 Orihuela CJ, Mahdavi J, Thornton J, Mann B, Wooldridge KG, Abouseada N, Oldfield NJ, Self T, Ala’Aldeen DA, Tuomanen EI (2009) Laminin receptor initiates bacterial contact with the blood brain barrier in experimental meningitis models. J Clin Investig 119:1638–1646. doi:10.1172/JCI36759 Ostergaard C, Benfield T, Gesser B, Kharazmi A, Frimodt-Moller N, Espersen F, Lundgren JD (1999) Pretreatment with granulocyte colony-stimulating factor attenuates the inflammatory response but not the bacterial load in cerebrospinal fluid during experimental pneumococcal meningitis in rabbits. Infect Immun 67:3430–3436 Patterson H, Saralahti A, Parikka M, Dramsi S, Trieu-Cuot P, Poyart C, Rounioja S, Ramet M (2012) Adult zebrafish model of bacterial meningitis in Streptococcus agalactiae infection. Dev Comp Immunol 38:447–455. doi:10.1016/j.dci.2012.07.007 Paul R, Koedel U, Pfister HW (2003) Using knockout mice to study experimental meningitis. Arch Immunol Ther Exp 51:315–326 Pautsch A, Schulz GE (2000) High-resolution structure of the OmpA membrane domain. J Mol Biol 298:273–282. doi:10.1006/jmbi.2000.3671 Petersdorf RG, Swarner DR, Garcia M (1962) Studies on the pathogenesis of meningitis. II. Development of meningitis during pneumococcal bacteremia. J Clin Investig 41:320–327. doi:10.1172/JCI104485 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 Prasadarao NV, Srivastava PK, Rudrabhatla RS, Kim KS, Huang SH, Sukumaran SK (2003) Cloning and expression of the Escherichia coli K1 outer membrane protein A receptor, a gp96 homologue. Infect Immun 71:1680–1688. doi:10.1128/Iai.71.4.1680-1688.2003 Prasadarao NV, Wass CA, Kim KS (1996) Endothelial cell GlcNAc beta 1-4GlcNAc epitopes for outer membrane protein A enhance traversal of Escherichia coli across the blood-brain barrier. Infect Immun 64:154–160 Pron B, Taha MK, Rambaud C, Fournet JC, Pattey N, Monnet JP, Musilek M, Beretti JL, Nassif X (1997) Interaction of Neisseria meningitidis with the components of the blood-brain barrier correlates with an increased expression of PilC. J Infect Dis 176:1285–1292 Quach D, van Sorge NM, Kristian SA, Bryan JD, Shelver DW, Doran KS (2009) The CiaR response regulator in group B Streptococcus promotes intracellular survival and resistance to innate immune defenses. J Bacteriol 191:2023–2032. doi:10.1128/JB.01216-08 Quirante J, Ceballos R, Cassady G (1974) Group B beta-hemolytic streptococcal infection in the newborn. I. Early onset infection. Am J Dis Child 128:659–665 Radin JN, Orihuela CJ, Murti G, Guglielmo C, Murray PJ, Tuomanen EI (2005) Beta-arrestin 1 participates in platelet-activating factor receptor-mediated endocytosis of Streptococcus pneumoniae. Infect Immun 73:7827–7835. doi:10.1128/IAI.73.12.7827-7835.2005 Reddy MA, Prasadarao NV, Wass CA, Kim KS (2000) Phosphatidylinositol 3-kinase activation and interaction with focal adhesion kinase in Escherichia coli K1 invasion of human brain microvascular endothelial cells. J Biol Chem 275:36769–36774. doi:10.1074/jbc.M007382200 Reddy MA, Wass CA, Kim KS, Schlaepfer DD, Prasadarao NV (2000) Involvement of focal adhesion kinase in Escherichia coli invasion of human brain microvascular endothelial cells. Infect Immun 68:6423–6430 Reiss A, Braun JS, Jager K, Freyer D, Laube G, Buhrer C, Felderhoff-Muser U, Stadelmann C, Nizet V, Weber JR (2011) Bacterial pore-forming cytolysins induce neuronal damage in a rat model of neonatal meningitis. J Infect Dis 203:393–400. doi:10.1093/infdis/jiq047 Ring A, Weiser JN, Tuomanen EI (1998) Pneumococcal trafficking across the blood-brain barrier. Molecular analysis of a novel bidirectional pathway. J Clin Investig 102:347–360. doi:10.1172/JCI2406 Rosenstein NE, Perkins BA, Stephens DS, Popovic T, Hughes JM (2001) Meningococcal disease. N Engl J Med 344:1378–1388. doi:10.1056/NEJM200105033441807 Rubens CE, Wessels MR, Heggen LM, Kasper DL (1987) Transposon mutagenesis of type III group B Streptococcus: correlation of capsule expression with virulence. Proc Natl Acad Sci USA 84:7208–7212 Sa ECC, Griffiths NJ, Virji M (2010) Neisseria meningitidis Opc invasin binds to the sulphated tyrosines of activated vitronectin to attach to and invade human brain endothelial cells. PLoS Pathog 6:e1000911. doi:10.1371/journal.ppat.1000911 Sadarangani M, Pollard AJ, Gray-Owen SD (2011) Opa proteins and CEACAMs: pathways of immune engagement for pathogenic Neisseria. FEMS Microbiol Rev 35:498–514. doi:10.1111/j.1574-6976.2010.00260.x Sarkari J, Pandit N, Moxon ER, Achtman M (1994) Variable expression of the Opc outer membrane protein in Neisseria meningitidis is caused by size variation of a promoter containing poly-cytidine. Mol Microbiol 13:207–217 Scheld WM, Koedel U, Nathan B, Pfister HW (2002) Pathophysiology of bacterial meningitis: mechanism(s) of neuronal injury. J Infect Dis 186(Suppl 2):S225–S233. doi:10.1086/344939 Schubert-Unkmeir A, Konrad C, Slanina H, Czapek F, Hebling S, Frosch M (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. doi:10.1371/journal.ppat.1000874 Seele J, Beineke A, Hillermann LM, Jaschok-Kentner B, von Pawel-Rammingen U, Valentin-Weigand P, Baums CG (2015) The immunoglobulin M-degrading enzyme of Streptococcus suis, IdeSsuis, is involved in complement evasion. Vet Res 46:45. doi:10.1186/s13567-015-0171-6 Seitz M, Baums CG, Neis C, Benga L, Fulde M, Rohde M, Goethe R, Valentin-Weigand P (2013) Subcytolytic effects of suilysin on interaction of Streptococcus suis with epithelial cells. Vet Microbiol 167:584–591. doi:10.1016/j.vetmic.2013.09.010 Selvaraj SK, Periandythevar P, Prasadarao NV (2007) Outer membrane protein A of Escherichia coli K1 selectively enhances the expression of intercellular adhesion molecule-1 in brain microvascular endothelial cells. Microbes Infect/Inst Pasteur 9:547–557. doi:10.1016/j.micinf.2007.01.020 Selvaraj SK, Prasadarao NV (2005) Escherichia coli K1 inhibits proinflammatory cytokine induction in monocytes by preventing NF-kappaB activation. J Leukoc Biol 78:544–554. doi:10.1189/jlb.0904516 Seo HS, Minasov G, Seepersaud R, Doran KS, Dubrovska I, Shuvalova L, Anderson WF, Iverson TM, Sullam PM (2013) Characterization of fibrinogen binding by glycoproteins Srr1 and Srr2 of Streptococcus agalactiae. J Biol Chem 288:35982–35996. doi:10.1074/jbc.M113.513358 Seo HS, Mu R, Kim BJ, Doran KS, Sullam PM (2012) Binding of glycoprotein Srr1 of Streptococcus agalactiae to fibrinogen promotes attachment to brain endothelium and the development of meningitis. PLoS Pathog 8:e1002947. doi:10.1371/journal.ppat.1002947 Shanmuganathan MV, Krishnan S, Fu X, Prasadarao NV (2013) Attenuation of biopterin synthesis prevents Escherichia coli K1 invasion of brain endothelial cells and the development of meningitis in newborn mice. J Infect Dis 207:61–71. doi:10.1093/infdis/jis656 Shanmuganathan MV, Krishnan S, Fu X, Prasadarao NV (2014) Escherichia coli K1 induces pterin production for enhanced expression of Fcgamma receptor I to invade RAW 264.7 macrophages. Microbes Infect/Inst Pasteur 16:134–141. doi:10.1016/j.micinf.2013.10.013 Simonis A, Hebling S, Gulbins E, Schneider-Schaulies S, Schubert-Unkmeir A (2014) Differential activation of acid sphingomyelinase and ceramide release determines invasiveness of Neisseria meningitidis into brain endothelial cells. PLoS Pathog 10:e1004160. doi:10.1371/journal.ppat.1004160 Slanina H, Hebling S, Hauck CR, Schubert-Unkmeir A (2012) Cell invasion by Neisseria meningitidis requires a functional interplay between the focal adhesion kinase, Src and cortactin. PloS One 7:e39613. doi:10.1371/journal.pone.0039613 Slanina H, Konig A, Hebling S, Hauck CR, Frosch M, Schubert-Unkmeir A (2010) Entry of Neisseria meningitidis into mammalian cells requires the Src family protein tyrosine kinases. Infect Immun 78:1905–1914. doi:10.1128/IAI.01267-09 Slanina H, Mundlein S, Hebling S, Schubert-Unkmeir A (2014) Role of epidermal growth factor receptor signaling in the interaction of Neisseria meningitidis with endothelial cells. Infect Immun 82:1243–1255. doi:10.1128/IAI.01346-13 Smith SG, Mahon V, Lambert MA, Fagan RP (2007) A molecular Swiss army knife: OmpA structure, function and expression. FEMS Microbiol Lett 273:1–11. doi:10.1111/j.1574-6968.2007.00778.x Sokolova O, Heppel N, Jagerhuber R, Kim KS, Frosch M, Eigenthaler M, Schubert-Unkmeir A (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. doi:10.1111/j.1462-5822.2004.00422.x Stins MF, Prasadarao NV, Ibric L, Wass CA, Luckett P, Kim KS (1994) Binding characteristics of S fimbriated Escherichia coli to isolated brain microvascular endothelial cells. Am J Pathol 145:1228–1236 Sukumaran SK, McNamara G, Prasadarao NV (2003) Escherichia coli K-1 interaction with human brain micro-vascular endothelial cells triggers phospholipase C-gamma1 activation downstream of phosphatidylinositol 3-kinase. J Biol Chem 278:45753–45762. doi:10.1074/jbc.M307374200 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. doi:10.1086/379042 Sukumaran SK, Quon MJ, Prasadarao NV (2002) Escherichia coli K1 internalization via caveolae requires caveolin-1 and protein kinase Calpha interaction in human brain microvascular endothelial cells. J Biol Chem 277:50716–50724. doi:10.1074/jbc.M208830200 Sukumaran SK, Selvaraj SK, Prasadarao NV (2004) Inhibition of apoptosis by Escherichia coli K1 is accompanied by increased expression of BClXL and blockade of mitochondrial cytochrome c release in macrophages. Infect Immun 72:6012–6022. doi:10.1128/Iai.72.10.6012-6022.2004 Sukumaran SK, Shimada H, Prasadarao NV (2003) Entry and intracellular replication of Escherichia coli K1 in macrophages require expression of outer membrane protein A. Infect Immun 71:5951–5961 Tauber MG, Kennedy SL, Tureen JH, Lowenstein DH (1992) Experimental pneumococcal meningitis causes central nervous system pathology without inducing the 72-kd heat shock protein. Am J Pathol 141:53–60 Tazi A, Disson O, Bellais S, Bouaboud A, Dmytruk N, Dramsi S, Mistou MY, Khun H, Mechler C, Tardieux I, Trieu-Cuot P, Lecuit M, Poyart C (2010) The surface protein HvgA mediates group B streptococcus hypervirulence and meningeal tropism in neonates. J Exp Med 207:2313–2322. doi:10.1084/jem.20092594 Tenenbaum T, Matalon D, Adam R, Seibt A, Wewer C, Schwerk C, Galla HJ, Schroten H (2008) Dexamethasone prevents alteration of tight junction-associated proteins and barrier function in porcine choroid plexus epithelial cells after infection with Streptococcus suis in vitro. Brain Res 1229:1–17. doi:10.1016/j.brainres.2008.06.118 Tenenbaum T, Papandreou T, Gellrich D, Friedrichs U, Seibt A, Adam R, Wewer C, Galla HJ, Schwerk C, Schroten H (2009) Polar bacterial invasion and translocation of Streptococcus suis across the blood-cerebrospinal fluid barrier in vitro. Cell Microbiol 11:323–336. doi:10.1111/j.1462-5822.2008.01255.x Teng CH, Cai M, Shin S, Xie Y, Kim KJ, Khan NA, Di Cello F, Kim KS (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. doi:10.1128/IAI.73.5.2923-2931.2005 Tibussek D, Sinclair A, Yau I, Teatero S, Fittipaldi N, Richardson SE, Mayatepek E, Jahn P, Askalan R (2015) Late-onset group B streptococcal meningitis has cerebrovascular complications. J Pediatr 166(1187–1192):e1181. doi:10.1016/j.jpeds.2015.02.014 Tuomanen E, Liu H, Hengstler B, Zak O, Tomasz A (1985) The induction of meningeal inflammation by components of the pneumococcal cell wall. J Infect Dis 151:859–868 Uchiyama S, Carlin AF, Khosravi A, Weiman S, Banerjee A, Quach D, Hightower G, Mitchell TJ, Doran KS, Nizet V (2009) The surface-anchored NanA protein promotes pneumococcal brain endothelial cell invasion. J Exp Med 206:1845–1852. doi:10.1084/jem.20090386 Unkmeir A, Latsch K, Dietrich G, Wintermeyer E, Schinke B, Schwender S, Kim KS, Eigenthaler M, Frosch M (2002) Fibronectin mediates Opc-dependent internalization of Neisseria meningitidis in human brain microvascular endothelial cells. Mol Microbiol 46:933–946 Vadeboncoeur N, Segura M, Al-Numani D, Vanier G, Gottschalk M (2003) Pro-inflammatory cytokine and chemokine release by human brain microvascular endothelial cells stimulated by Streptococcus suis serotype 2. FEMS Immunol Med Microbiol 35:49–58 Van Calsteren MR, Gagnon F, Lacouture S, Fittipaldi N, Gottschalk M (2010) Structure determination of Streptococcus suis serotype 2 capsular polysaccharide. Biochem cell Biol Biochim Biol Cellulaire 88:513–525. doi:10.1139/o09-170 van Ginkel FW, McGhee JR, Watt JM, Campos-Torres A, Parish LA, Briles DE (2003) Pneumococcal carriage results in ganglioside-mediated olfactory tissue infection. Proc Natl Acad Sci USA 100:14363–14367. doi:10.1073/pnas.2235844100 van Putten JP, Paul SM (1995) Binding of syndecan-like cell surface proteoglycan receptors is required for Neisseria gonorrhoeae entry into human mucosal cells. The EMBO J 14:2144–2154 Virji M (2009) Pathogenic neisseriae: surface modulation, pathogenesis and infection control. Nat Rev Microbiol 7:274–286. doi:10.1038/nrmicro2097 Waage A, Brandtzaeg P, Halstensen A, Kierulf P, Espevik T (1989) The complex pattern of cytokines in serum from patients with meningococcal septic shock. Association between interleukin 6, interleukin 1, and fatal outcome. J Exp Med 169:333–338 Watt JP, Wolfson LJ, O’Brien KL, Henkle E, Deloria-Knoll M, McCall N, Lee E, Levine OS, Hajjeh R, Mulholland K, Cherian T, Hib, Pneumococcal Global Burden of Disease Study T (2009) Burden of disease caused by Haemophilus influenzae type b in children younger than 5 years: global estimates. Lancet 374:903–911. doi:10.1016/S0140-6736(09)61203-4 Wertheim HF, Nghia HD, Taylor W, Schultsz C (2009) Streptococcus suis: an emerging human pathogen. Clin Infect Dis Off Publ Infect Dis Soc Am 48:617–625. doi:10.1086/596763 Wewer C, Seibt A, Wolburg H, Greune L, Schmidt MA, Berger J, Galla HJ, Quitsch U, Schwerk C, Schroten H, Tenenbaum T (2011) Transcellular migration of neutrophil granulocytes through the blood-cerebrospinal fluid barrier after infection with Streptococcus suis. J Neuroinflamm 8:51. doi:10.1186/1742-2094-8-51 Whalen CM, Hockin JC, Ryan A, Ashton F (1995) The changing epidemiology of invasive meningococcal disease in Canada, 1985 through 1992. Emergence of a virulent clone of Neisseria meningitidis. JAMA 273:390–394 Willenborg J, Fulde M, de Greeff A, Rohde M, Smith HE, Valentin-Weigand P, Goethe R (2011) Role of glucose and CcpA in capsule expression and virulence of Streptococcus suis. Microbiology 157:1823–1833. doi:10.1099/mic.0.046417-0 Wippel C, Maurer J, Fortsch C, Hupp S, Bohl A, Ma J, Mitchell TJ, Bunkowski S, Bruck W, Nau R, Iliev AI (2013) Bacterial cytolysin during meningitis disrupts the regulation of glutamate in the brain, leading to synaptic damage. PLoS Pathog 9:e1003380. doi:10.1371/journal.ppat.1003380 Wooster DG, Maruvada R, Blom AM, Prasadarao NV (2006) Logarithmic phase Escherichia coli K1 efficiently avoids serum killing by promoting C4 bp-mediated C3b and C4b degradation. Immunology 117:482–493. doi:10.1111/j.1365-2567.2006.02323.x Wu Z, Wu C, Shao J, Zhu Z, Wang W, Zhang W, Tang M, Pei N, Fan H, Li J, Yao H, Gu H, Xu X, Lu C (2014) The Streptococcus suis transcriptional landscape reveals adaptation mechanisms in pig blood and cerebrospinal fluid. RNA 20:882–898. doi:10.1261/rna.041822.113 Zhang A, Mu X, Chen B, Liu C, Han L, Chen H, Jin M (2010) Identification and characterization of IgA1 protease from Streptococcus suis. Vet Microbiol 140:171–175. doi:10.1016/j.vetmic.2009.06.034 Zhang JR, Mostov KE, Lamm ME, Nanno M, Shimida S, Ohwaki M, Tuomanen E (2000) The polymeric immunoglobulin receptor translocates pneumococci across human nasopharyngeal epithelial cells. Cell 102:827–837 Zheng H, Sun H, Dominguez-Punaro Mde L, Bai X, Ji S, Segura M, Xu J (2013) Evaluation of the pathogenesis of meningitis caused by Streptococcus suis sequence type 7 using the infection of BV2 microglial cells. J Med Microbiol 62:360–368. doi:10.1099/jmm.0.046698-0 Zysk G, Bruck W, Gerber J, Bruck Y, Prange HW, Nau R (1996) Anti-inflammatory treatment influences neuronal apoptotic cell death in the dentate gyrus in experimental pneumococcal meningitis. J Neuropathol Exp Neurol 55:722–728 Zysk G, Schneider-Wald BK, Hwang JH, Bejo L, Kim KS, Mitchell TJ, Hakenbeck R, Heinz HP (2001) Pneumolysin is the main inducer of cytotoxicity to brain microvascular endothelial cells caused by Streptococcus pneumoniae. Infect Immun 69:845–852. doi:10.1128/Iai.69.2.845-852.2001