Streptococcus pneumoniae: Invasion and Inflammation

Carlos J. Orihuela; Elaine Tuomanen

doi:10.1128/9781555816513.ch21

Chapter 21 : Streptococcus pneumoniae: Invasion and Inflammation

Authors: Carlos J. Orihuela, Elaine Tuomanen

Content Type: Reference

Publication Year: 2006

Category: Bacterial Pathogenesis

Book DOI: 10.1128/9781555816513

Chapter DOI: 10.1128/9781555816513.ch21

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Abstract:

Streptococcus pneumoniae (the pneumococcus) is the leading cause of otitis media (OM), community-acquired pneumonia, and bacterial meningitis. Pneumococcal models of invasive disease must account for the commensal nature of the bacteria, yet also take into account the wide spectrum of disease the pneumococcus is capable of causing. This chapter first reviews the molecular mechanisms that allow the pneumococcus to colonize and spread from one anatomical site to the next. Then, it discusses the mechanisms of inflammation and cytotoxicity during pneumococcal infection.

Citation: Orihuela C, Tuomanen E. 2006. Streptococcus pneumoniae: Invasion and Inflammation, p 253-267. In Fischetti V, Novick R, Ferretti J, Portnoy D, Rood J (ed), Gram-Positive Pathogens, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816513.ch21

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Streptococcus pneumoniae: Invasion and Inflammation

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FIGURE 1

(See the separate color insert for the color version of this illustration.) Immuno-histochemical and schematic depiction of the choline biology of the pneumococcal surface. Immunogold-labeling of pneumococci with (A) TEPC-15 antibody recognizing free choline and (B) antiautolysin antibody. These two images contrast free (A) versus CBP-bound (B) choline. (C) Schematic view of the capsule (blue), cell wall (green), and membrane (red). The teichoic and lipoteichoic acids are indicated as dark blue lines bearing choline (circles). A proportion of these are capped by CBPs. (Courtesy of Dr. K. G. Murti, St. Jude Electron Microscopy Core Facility.)

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FIGURE 1

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FIGURE 2

(A) Graphical representation of the CBP LytA ( 36 ). Boxes indicate individual choline-binding repeats (CBR), each consisting of the consensus sequence GWVKD-NGTWYYLNSSGAMAT. CBPs attach noncovalently to ChoP on the bacterial surface through the choline-binding domain (CBD), which typically consists of multiple CBRs. Crystal structure analysis of the CBD of LytA, the major autolysin, indicates that each 20-amino-acid CBR forms a small hairpin consisting of two antiparallel β-strands connected by a short internal loop. (B) These hairpins are connected by 8 to 10 residues that rotate each hairpin in a 120° counterclockwise direction such that a left-handed superhelix is formed, similar to a spiral staircase. ChoP is subsequently bound by hydrophobic cavities present in the grooves of the surface of the CBD steps ( 31 ).

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FIGURE 2

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FIGURE 3

Microscopic and schematic depictions of pneumococcal invasion. (Top) Pneumococci (dark blue gram positive) bind to and are internalized into type II A549 lung cells on top of a microporous filter. Upon exiting the base of the lung cell the bacteria pass through the filter pores and invade and transcytose across primary human endothelial cells under the filter. Courtesy of Dr. C. Rosenow, Rockefeller University. (Bottom) The schematic illustrates the differences in the transcytosis process between opaque and transparent phase variants (transparent/opaque). Three fates are: (i) entry and recycling to the apical surface favored for the transparent bacteria and inhibitable by PAF receptor antagonist (PAF Ra); (ii) entry and death within the vacuole favored for opaque bacteria; and (iii) entry and transmigration across the cell, overwhelmingly favored by transparent bacteria. (Modified from reference 92 .)

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FIGURE 3

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FIGURE 4

Structure of the pneumococcal cell wall and its relationship to inflammation. (A) Penicillin induces cell wall degradation by the autolysin, releasing cell wall fragments such as lipoteichoic acid, glycan polymers with and without teichoic acid, and small stem peptides. All teichoicated species contain ChoP, a key component increasing inflammatory activity. (B) All of these components interact with a variety of human cells, which in turn produce inflammatory mediators. Particularly important in this response are PAF and IL-1. These mediators combine to produce the symptomatology of pneumococcal infection, including changes in blood flow, fluid balance in the tissue, and leukocytosis. Glc: glucose; TDH: trideoxyhexose; NAcGaln: N-acetylgalactosamine; Galn: galactosamine; L-Ala: L-alanine; D-Glu: D-glucose; L-Lys: L-lysine; TNF: tumor necrosis factor; NO: nitric oxide; PGE2: prostaglandin E2; IC: intracranial.

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FIGURE 4

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FIGURE 5

Domain structure of pneumolysin. Pneumolysin has three functionally separate domains: one activating complement, one causing hemolysis, and the other binding to cholesterol. Site-specific mutations alter these properties individually. (Compiled from references 94 and 97 .)

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FIGURE 5

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FIGURE 6

Site-specific contribution of pneumococcal virulence factors to survival and transitions from one anatomical site to the next. (Reproduced with permission from reference 80 .)

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FIGURE 6

Site-specific contribution of pneumococcal virulence factors to survival and transitions from one anatomical site to the next. (Reproduced with permission from reference 80 .)

References

/content/book/10.1128/9781555816513.chap21

1. Abeyta, M.,, G. G. Hardy,, and J. Yother. 2003. Genetic alteration of capsule type but not PspA type affects accessibility of surface-bound complement and surface antigens of Streptococcus pneumoniae. Infect. Immun. 71: 218– 225.

2. Alcantara, R. B.,, L. C. Preheim,, and M. J. Gentry. 1999. Role of pneumolysin’s complement-activating activity during pneumococcal bacteremia in cirrhotic rats. Infect. Immun. 67: 2862– 2866.

3. Alcantara, R. B.,, L. C. Preheim,, and M. J. Gentry-Nielsen. 2001. Pneumolysin-induced complement depletion during experimental pneumococcal bacteremia. Infect. Immun. 69: 3569– 3575.

4. Austrian, R. 1986. Some aspects of the pneumococcal carrier state. J. Antimicrob. Chemother. 18(Suppl. A): 35– 45.

5. Balachandran, P.,, S. K. Hollingshead,, J. C. Paton,, and D. E. Briles. 2001. The autolytic enzyme LytA of Streptococcus pneumoniae is not responsible for releasing pneumolysin. J. Bacteriol. 183: 3108– 3116.

6. Berry, A. M.,, and J. C. Paton. 2000. Additive attenuation of virulence of Streptococcus pneumoniae by mutation of the genes encoding pneumolysin and other putative pneumococcal virulence proteins. Infect. Immun. 68: 133– 140.

7. Berry, A. M.,, J. C. Paton,, and D. Hansman. 1992. Effect of insertional inactivation of the genes encoding pneumolysin and autolysin on the virulence of Streptococcus pneumoniae type 3. Microb. Pathog. 12: 87– 93.

8. Berry, A. M.,, R. A. Lock,, and J. C. Paton. 1996. Cloning and characterization of nanB, a second Streptococcus pneumoniae neuraminidase gene, and purification of the NanB enzyme from recombinant Escherichia coli. J. Bacteriol. 178: 4854– 4860.

9. Block, S. L. 1997. Causative pathogens, antibiotic resistance and therapeutic considerations in acute otitis media. Pediatr. Infect. Dis. J. 16: 449– 456.

10. Braun, J. S.,, R. Novak,, K. H. Herzog,, S. M. Bodner,, J. L. Cleveland,, and E. I. Tuomanen. 1999. Neuroprotection by a caspase inhibitor in acute bacterial meningitis. Nat. Med. 5: 298– 302.

11. Braun, J. S.,, J. E. Sublett,, D. Freyer,, T. J. Mitchell,, J. L. Cleveland,, E. I. Tuomanen,, and J. R. Weber. 2002. Pneumococcal pneumolysin and H(2)O(2) mediate brain cell apoptosis during meningitis. J. Clin. Invest. 109: 19– 27.

12. Briles, D. E.,, M. J. Crain,, B. M. Gray,, C. Forman,, and J. Yother. 1992. Strong association between capsular type and virulence for mice among human isolates of Streptococcus pneumoniae. Infect. Immun. 60: 111– 116.

13. Brown, J. S.,, S. M. Gilliland,, and D. W. Holden. 2001. A Streptococcus pneumoniae pathogenicity island encoding an ABC transporter involved in iron uptake and virulence. Mol. Microbiol. 40: 572– 585.

14. Brueggemann, A. B.,, T. E. Peto,, D. W. Crook,, J. C. Butler,, K. G. Kristinsson,, and B. G. Spratt. 2004. Temporal and geographic stability of the serogroup-specific invasive disease potential of Streptococcus pneumoniae in children. J. Infect. Dis. 190: 1203– 1211.

15. Butler, J. C., 2004. Epidemiology of pneumococcal disease, p. 148– 168. In E. I. Tuomanen,, T. J. Mitchell,, D. A. Morrison,, and B. G. Spratt (ed.), The Pneumococcus. ASM Press, Washington, D.C.

16. Canvin, J. R.,, A. P. Marvin,, M. Sivakumaran,, J. C. Paton,, G. J. Boulnois,, P. W. Andrew,, and T. J. Mitchell. 1995. The role of pneumolysin and autolysin in the pathology of pneumonia and septicemia in mice infected with a type 2 pneumococcus. J. Infect. Dis. 172: 119– 123.

17.Centers for Disease Control and Prevention. 1997. Prevention of pneumococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP). Morb. Mortal. Wkly. Rep. 46: 1– 25.

18. Cockeran, R.,, A. J. Theron,, C. Feldman,, T. J. Mitchel,, and R. Anderson. 2004. Pneumolysin potentiates oxidative inactivation of alpha-1-proteinase inhibitor by activated human neutrophils. Respir. Med. 98: 865– 871.

19. Comis, S. D.,, M. P. Osborne,, J. Stephen,, M. J. Tarlow,, T. L. Hayward,, T. J. Mitchell,, P. W. Andrew,, and G. J. Boulnois. 1993. Cytotoxic effects on hair cells of guinea pig cochlea produced by pneumolysin, the thiol activated toxin of Streptococcus pneumoniae. Acta Otolaryngol. 113: 152– 159.

20. Crook, D. W.,, A. B. Brueggemann,, K. L. Sleeman,, and T. E. A. Peto,. 2004. Pneumococcal carriage, p. 136– 147. In E. I. Tuomanen,, T. J. Mitchell,, D. A. Morrison,, and B. G. Spratt (ed.), The Pneumococcus. ASM Press, Washington, D.C.

21. Cundell, D. R.,, N. P. Gerard,, C. Gerard,, I. Idanpaan-Heikkila,, and E. I. Tuomanen. 1995. Streptococcus pneumoniae anchor to activated human cells by the receptor for platelet-activating factor. Nature 377: 435– 438.

22. Dave, S.,, M. K. Pangburn,, C. Pruitt,, and L. S. McDaniel. 2004. Interaction of human factor H with PspC of Streptococcus pneumoniae. Indian J. Med. Res. 119(Suppl.): 66– 73.

23. Davidson, M.,, A. J. Parkinson,, L. R. Bulkow,, M. A. Fitzgerald,, H. V. Peters,, and D. J. Parks. 1994. The epidemiology of invasive pneumococcal disease in Alaska, 1986-1990—ethnic differences and opportunities for prevention. J. Infect. Dis. 170: 368– 376.

24. de Gans, J.,, and D. van de Beek. 2002. Dexamethasone in adults with bacterial meningitis. N. Engl. J. Med. 347: 1549– 1556.

25. Dopazo, J.,, A. Mendoza,, J. Herrero,, F. Caldara,, Y. Humbert,, L. Friedli,, M. Guerrier,, E. Grand-Schenk,, C. Gandin,, M. de Francesco,, A. Polissi,, G. Buell,, G. Feger,, E. Garcia,, M. Peitsch,, and J. F. Garcia-Bustos. 2001. Annotated draft genomic sequence from a Streptococcus pneumoniae type 19F clinical isolate. Microb. Drug Resist. 7: 99– 125.

26. Dunais, B.,, C. Pradier,, H. Carsenti,, M. Sabah,, G. Mancini,, E. Fontas,, and P. Dellamonica. 2003. Influence of child care on nasopharyngeal carriage of Streptococcus pneumoniae and Haemophilus influenzae. Pediatr. Infect. Dis. J. 22: 589– 592.

27. Durand, M. L.,, S. B. Calderwood,, D. J. Weber,, S. I. Miller,, F. S. Southwick,, V. S. Caviness, Jr.,, and M. N. Swartz. 1993. Acute bacterial meningitis in adults. A review of 493 episodes. N. Engl. J. Med. 328: 21– 28.

28. Duthy, T. G.,, R. J. Ormsby,, E. Giannakis,, A. D. Ogunniyi,, U. H. Stroeher,, J. C. Paton,, and D. L. Gordon. 2002. The human complement regulator factor H binds pneumococcal surface protein PspC via short consensus repeats 13 to 15. Infect. Immun. 70: 5604– 5611.

29. Fedson, D. S.,, D. M. Musher,, and J. Eskola,. 1998. Pneumococcal vaccine, p. 32– 48. In S. A. Plotkin, and W. A. Ordenstein (ed.), Vaccines, 3rd ed. WB Saunders, Philadelphia, Pa.

30. Feldman, C.,, R. Anderson,, R. Cockeran,, T. Mitchell,, P. Cole,, and R. Wilson. 2002. The effects of pneumolysin and hydrogen peroxide, alone and in combination, on human ciliated epithelium in vitro. Respir. Med. 96: 580– 585.

31. Fernandez-Tornero, C.,, R. Lopez,, E. Garcia,, G. Gimenez-Gallego,, and A. Romero. 2001. A novel solenoid fold in the cell wall anchoring domain of the pneumococcal virulence factor LytA. Nat. Struct. Biol. 8: 1020– 1024.

32. Fine, D. P. 1975. Pneumococcal type-associated variability in alternate complement pathway activation. Infect. Immun. 12: 772– 778.

33. Fiore, A. E.,, O. S. Levine,, J. A. Elliott,, R. R. Facklam,, and J. C. Butler. 1999. Effectiveness of pneumococcal polysaccharide vaccine for preschool-age children with chronic disease. Emerg. Infect. Dis. 5: 828– 831.

34. Free, S. L.,, L. M. Li,, D. R. Fish,, S. D. Shorvon,, and J. M. Stevens. 1996. Bilateral hippocampal volume loss in patients with a history of encephalitis or meningitis. Epilepsia 37: 400– 405.

35. Freyer, D.,, R. Manz,, A. Ziegenhorn,, M. Weih,, K. Angstwurm,, W. D. Docke,, A. Meisel,, R. R. Schumann,, G. Schonfelder,, U. Dirnagl,, and J. R. Weber. 1999. Cerebral endothelial cells release TNF-alpha after stimulation with cell walls of Streptococcus pneumoniae and regulate inducible nitric oxide synthase and ICAM-1 expression via autocrine loops. J. Immunol. 163: 4308– 4314.

36. Garcia, E.,, J. L. Garcia,, C. Ronda,, P. Garcia,, and R. Lopez. 1985. Cloning and expression of the pneumococcal autolysin gene in Escherichia coli. Mol. Gen. Genet. 201: 225– 230.

37. Garcia, P.,, M. P. Gonzalez,, E. Garcia,, R. Lopez,, and J. L. Garcia. 1999. LytB, a novel pneumococcal murein hydrolase essential for cell separation. Mol. Microbiol. 31: 1275– 1277.

38. Garcia, P.,, M. Paz Gonzalez,, E. Garcia,, J. L. Garcia,, and R. Lopez. 1999. The molecular characterization of the first autolytic lysozyme of Streptococcus pneumoniae reveals evolutionary mobile domains. Mol. Microbiol. 33: 128– 138.

39. Gilbert, R. J.,, J. L. Jimenez,, S. Chen,, I. J. Tickle,, J. Rossjohn,, M. Parker,, P. W. Andrew,, and H. R. Saibil. 1999. Two structural transitions in membrane pore formation by pneumolysin, the pore-forming toxin of Streptococcus pneumoniae. Cell 97: 647– 655.

40. Girardin, S. E.,, I. G. Boneca,, L. A. Carneiro,, A. Antignac,, M. Jehanno,, J. Viala,, K. Tedin,, M. K. Taha,, A. Labigne,, U. Zahringer,, A. J. Coyle,, P. S. DiStefano,, J. Bertin,, P. J. Sansonetti,, and D. J. Philpott. 2003. Nod1 detects a unique muropeptide from gram-negative bacterial peptidoglycan. Science 300: 1584– 1587.

41. Gosink, K. K.,, E. R. Mann,, C. Guglielmo,, E. I. Tuomanen,, and H. R. Masure. 2000. Role of novel choline binding proteins in virulence of Streptococcus pneumoniae. Infect. Immun. 68: 5690– 5695.

42. Gould, J. M.,, and J. N. Weiser. 2001. Expression of C-reactive protein in the human respiratory tract. Infect. Immun. 69: 1747– 1754.

43. Gray, B. M.,, G. M. Converse III,, and H. C. Dillon, Jr. 1980. Epidemiologic studies of Streptococcus pneumoniae in infants: acquisition, carriage, and infection during the first 24 months of life. J. Infect. Dis. 142: 923– 933.

44. Gray, B. M.,, M. E. Turner,, and H. C. Dillon, Jr. 1982. Epidemiologic studies of Streptococcus pneumoniae in infants. The effects of season and age on pneumococcal acquisition and carriage in the first 24 months of life. Am. J. Epidemiol. 116: 692– 703.

45. Hakenbeck, R.,, N. Balmelle,, B. Weber,, C. Gardes,, W. Keck,, and A. de Saizieu. 2001. Mosaic genes and mosaic chromosomes: intra- and interspecies genomic variation of Streptococcus pneumoniae. Infect. Immun. 69: 2477– 2486.

46. Hanisch, U. K.,, M. Prinz,, K. Angstwurm,, K. G. Hausler,, O. Kann,, H. Kettenmann,, and J. R. Weber. 2001. The protein tyrosine kinase inhibitor AG126 prevents the massive microglial cytokine induction by pneumococcal cell walls. Eur. J. Immunol. 31: 2104– 2115.

47. Hava, D. L.,, and A. Camilli. 2002. Large-scale identification of serotype 4 Streptococcus pneumoniae virulence factors. Mol. Microbiol. 45: 1389– 1406.

48. Hemsley, C.,, E. Joyce,, D. L. Hava,, A. Kawale,, and A. Camilli. 2003. MgrA, an orthologue of Mga, acts as a transcriptional repressor of the genes within the rlrA pathogenicity islet in Streptococcus pneumoniae. J. Bacteriol. 185: 6640– 6647.

49. Hirst, R. A.,, A. Rutman,, K. Sikand,, P. W. Andrew,, T. J. Mitchell,, and C. O’Callaghan. 2000. Effect of pneumolysin on rat brain ciliary function: comparison of brain slices with cultured ependymal cells. Pediatr. Res. 47: 381– 384.

50. Hirst, R. A.,, K. S. Sikand,, A. Rutman,, T. J. Mitchell,, P. W. Andrew,, and C. O’Callaghan. 2000. Relative roles of pneumolysin and hydrogen peroxide from Streptococcus pneumoniae in inhibition of ependymal ciliary beat frequency. Infect. Immun. 68: 1557– 1562.

51. Holzer, T. J.,, K. M. Edwards,, H. Gewurz,, and C. Mold. 1984. Binding of C-reactive protein to the pneumococcal capsule or cell wall results in differential localization of C3 and stimulation of phagocytosis. J. Immunol. 133: 1424– 1430.

52. Hoskins, J.,, W. E. Alborn, Jr.,, J. Arnold,, L. C. Blaszczak,, S. Burgett,, B. S. DeHoff,, S. T. Estrem,, L. Fritz,, D. J. Fu,, W. Fuller,, C. Geringer,, R. Gilmour,, J. S. Glass,, H. Khoja,, A. R. Kraft,, R. E. Lagace,, D. J. LeBlanc,, L. N. Lee,, E. J. Lefkowitz,, J. Lu,, P. Matsushima,, S. M. McAhren,, M. McHenney,, K. Mcleaster,, C. W. Mundy,, T. I. Nicas,, F. H. Norris,, M. O’Gara,, R. B. Peery,, G. T. Robertson,, P. Rockey,, P. M. Sun,, M. E. Winkler,, Y. Yang,, M. Young-Bellido,, G. Zhao,, C. A. Zook,, R. H. Baltz,, S. R. Jaskunas,, P. R. Rosteck, Jr.,, P. L. Skatrud,, and J. I. Glass. 2001. Genome of the bacterium Streptococcus pneumoniae strain R6. J. Bacteriol. 183: 5709– 5717.

53. Hostetter, M. K. 1986. Serotypic variations among virulent pneumococci in deposition and degradation of covalently bound C3b: implications for phagocytosis and antibody production. J. Infect. Dis. 153: 682– 693.

54. Hostetter, M. K.,, M. L. Thomas,, F. S. Rosen,, and B. F. Tack. 1982. Binding of C3b proceeds by a transesterification reaction at the thiolester site. Nature 298: 72– 75.

55. Howie, A. J.,, and G. Brown. 1985. Effect of neuraminidase on the expression of the 3-fucosyl- N-acetyllactosamine antigen in human tissues. J. Clin. Pathol. 38: 409– 416.

56. Hummell, D. S.,, R. W. Berninger,, A. Tomasz,, and J. A. Winkelstein. 1981. The fixation of C3b to pneumococcal cell wall polymers as a result of activation of the alternative complement pathway. J. Immunol. 127: 1287– 1289.

57. Ibrahim, Y. M.,, A. R. Kerr,, J. McCluskey,, and T. J. Mitchell. 2004. Role of HtrA in the virulence and competence of Streptococcus pneumoniae. Infect. Immun. 72: 3584– 3591.

58. Jedrzejas, M. J. 2001. Pneumococcal virulence factors: structure and function. Microbiol. Mol. Biol. Rev. 65: 187– 207.

59. Kaetzel, C. S. 2001. Polymeric Ig receptor: defender of the fort or Trojan horse? Curr. Biol. 11: R35– R38.

60. Kastenbauer, S.,, U. Koedel,, and H. W. Pfister. 1999. Role of peroxynitrite as a mediator of pathophysiological alterations in experimental pneumococcal meningitis. J. Infect. Dis. 180: 1164– 1170.

61. Kelly, T.,, J. P. Dillard,, and J. Yother. 1994. Effect of genetic switching of capsular type on virulence of Streptococcus pneumoniae. Infect. Immun. 62: 1813– 1819.

62. Kilian, M.,, J. Mestecky,, and M. W. Russell. 1988. Defense mechanisms involving Fc-dependent functions of immunoglobulin A and their subversion by bacterial immunoglobulin A proteases. Microbiol. Rev. 52: 296– 303.

63. Kim, J. O.,, and J. N. Weiser. 1998. Association of intrastrain phase variation in quantity of capsular polysaccharide and teichoic acid with the virulence of Streptococcus pneumoniae. J. Infect. Dis. 177: 368– 377.

64. Kim, J. O.,, S. Romero-Steiner,, U. B. Sorensen,, J. Blom,, M. Carvalho,, S. Barnard,, G. Carlone,, and J. N. Weiser. 1999. Relationship between cell surface carbohydrates and intrastrain variation on opsonophagocytosis of Streptococcus pneumoniae. Infect. Immun. 67: 2327– 2333.

65. Kramer, M. R.,, B. Rudensky,, I. Hadas-Halperin,, M. Isacsohn,, and E. Melzer. 1987. Pneumococcal bacteremia—no change in mortality in 30 years: analysis of 104 cases and review of the literature. Isr. J. Med. Sci. 23: 174– 180.

66. Krivan, H. C.,, D. D. Roberts,, and V. Ginsburg. 1988. Many pulmonary pathogenic bacteria bind specifically to the carbohydrate sequence GalNAc beta 1-4Gal found in some glycolipids. Proc. Natl. Acad. Sci. USA 85: 6157– 6161.

67. Lau, G. W.,, S. Haataja,, M. Lonetto,, S. E. Kensit,, A. Marra,, A. P. Bryant,, D. McDevitt,, D. A. Morrison,, and D. W. Holden. 2001. A functional genomic analysis of type 3 Streptococcus pneumoniae virulence. Mol. Microbiol. 40: 555– 571.

68. Leibovitz, E. 2003. Acute otitis media in pediatric medicine: current issues in epidemiology, diagnosis, and management. Paediatr. Drugs 5(Suppl.): 1– 12.

69. Lu, L.,, M. E. Lamm,, H. Li,, B. Corthesy,, and J. R. Zhang. 2003. The human polymeric immunoglobulin receptor binds to Streptococcus pneumoniae via domains 3 and 4. J. Biol. Chem. 278: 48178– 48187.

70. Luton, F.,, M. Verges,, J. P. Vaerman,, M. Sudol,, and K. E. Mostov. 1999. The SRC family protein tyrosine kinase p62yes controls polymeric IgA transcytosis in vivo. Mol. Cell 4: 627– 632.

71. Magee, A. D.,, and J. Yother. 2001. Requirement for capsule in colonization by Streptococcus pneumoniae. Infect. Immun. 69: 3755– 3761.

72. Marra, A.,, J. Asundi,, M. Bartilson,, S. Lawson,, F. Fang,, J. Christine,, C. Wiesner,, D. Brigham,, W. P. Schneider,, and A. E. Hromockyj. 2002. Differential fluorescence induction analysis of Streptococcus pneumoniae identifies genes involved in pathogenesis. Infect. Immun. 70: 1422– 1433.

73. Maus, U. A.,, M. Srivastava,, J. C. Paton,, M. Mack,, M. B. Everhart,, T. S. Blackwell,, J. W. Christman,, D. Schlondorff,, W. Seeger,, and J. Lohmeyer. 2004. Pneumolysin-induced lung injury is independent of leukocyte trafficking into the alveolar space. J. Immunol. 173: 1307– 1312.

74. McCullers, J. A.,, and K. C. Bartmess. 2003. Role of neuraminidase in lethal synergism between influenza virus and Streptococcus pneumoniae. J. Infect. Dis. 187: 1000– 1009.

75. Melegaro, A.,, N. J. Gay,, and G. F. Medley. 2004. Estimating the transmission parameters of pneumococcal carriage in households. Epidemiol. Infect. 132: 433– 441.

76. Meli, D. N.,, S. Christen,, and S. L. Leib. 2003. Matrix metalloproteinase-9 in pneumococcal meningitis: activation via an oxidative pathway. J. Infect. Dis. 187: 1411– 1415.

77. Mitchell, T. J.,, P. W. Andrew,, F. K. Saunders,, A. N. Smith,, and G. J. Boulnois. 1991. Complement activation and antibody binding by pneumolysin via a region of the toxin homologous to a human acute-phase protein. Mol. Microbiol. 5: 1883– 1888.

78. Moreillon, P.,, and P. A. Majcherczyk. 2003. Proinflammatory activity of cell-wall constituents from gram-positive bacteria. Scand. J. Infect. Dis. 35: 632– 641.

79. Nau, R.,, and H. Eiffert. 2002. Modulation of release of proinflammatory bacterial compounds by antibacterials: potential impact on course of inflammation and outcome in sepsis and meningitis. Clin. Microbiol. Rev. 15: 95– 110.

80. Orihuela, C. J.,, G. Gao,, K. P. Francis,, J. Yu,, and E. I. Tuomanen. 2004. Tissue-specific contributions of pneumococcal virulence factors to pathogenesis. J. Infect. Dis. 190: 1661– 1669.

81. Orihuela, C. J.,, J. N. Radin,, J. E. Sublett,, G. Gao,, D. Kaushal,, and E. Tuomanen. 2004. Microarray analysis of pneumococcal gene expression during invasive disease. Infect. Immun. 72: 5582– 5596.

82. Ozinsky, A.,, D. M. Underhill,, J. D. Fontenot,, A. M. Hajjar,, K. D. Smith,, C. B. Wilson,, L. Schroeder,, and A. Aderem. 2000. The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between toll-like receptors. Proc. Natl. Acad. Sci. USA 97: 13766– 13771.

83. Paton, J. C.,, and A. Ferrante. 1983. Inhibition of human polymorphonuclear leukocyte respiratory burst, bactericidal activity, and migration by pneumolysin. Infect. Immun. 41: 1212– 1216.

84. Peltola, V. T.,, and J. A. McCullers. 2004. Respiratory viruses predisposing to bacterial infections: role of neuraminidase. Pediatr. Infect. Dis. J. 23: S87– S97.

85. Polissi, A.,, A. Pontiggia,, G. Feger,, M. Altieri,, H. Mottl,, L. Ferrari,, and D. Simon. 1998. Large-scale identification of virulence genes from Streptococcus pneumoniae. Infect. Immun. 66: 5620– 5629.

86. Porat, N.,, R. Trefler,, and R. Dagan. 2001. Persistence of two invasive Streptococcus pneumoniae clones of serotypes 1 and 5 in comparison to that of multiple clones of serotypes 6B and 23F among children in southern Israel. J. Clin. Microbiol. 39: 1827– 1832.

87. Radin, J. N.,, C. J. Orihuela,, G. Murti,, C. Guglielmo,, P. J. Murray,, and E. Tuomanen. 2005. B-arrestin 1 determines the traffic pattern of PAFr-mediated endocytosis of Streptococcus pneumoniae. Infect. Immun. 73: 7827– 7835.

88. Rayner, C. F.,, A. D. Jackson,, A. Rutman,, A. Dewar,, T. J. Mitchell,, P. W. Andrew,, P. J. Cole,, and R. Wilson. 1995. Interaction of pneumolysin-sufficient and -deficient isogenic variants of Streptococcus pneumoniae with human respiratory mucosa. Infect. Immun. 63: 442– 447.

89. Regev-Yochay, G.,, M. Raz,, R. Dagan,, N. Porat,, B. Shainberg,, E. Pinco,, N. Keller,, and E. Rubinstein. 2004. Nasopharyngeal carriage of Streptococcus pneumoniae by adults and children in community and family settings. Clin. Infect. Dis. 38: 632– 639.

90. Ren, B.,, A. J. Szalai,, O. Thomas,, S. K. Hollingshead,, and D. E. Briles. 2003. Both family 1 and family 2 PspA proteins can inhibit complement deposition and confer virulence to a capsular serotype 3 strain of Streptococcus pneumoniae. Infect. Immun. 71: 75– 85.

91. Ren, B.,, A. J. Szalai,, S. K. Hollingshead,, and D. E. Briles. 2004. Effects of PspA and antibodies to PspA on activation and deposition of complement on the pneumococcal surface. Infect. Immun. 72: 114– 122.

92. Ring, A.,, J. N. Weiser,, and E. I. Tuomanen. 1998. Pneumococcal trafficking across the blood-brain barrier. Molecular analysis of a novel bidirectional pathway. J. Clin. Invest. 102: 347– 360.

93. Rosenow, C.,, P. Ryan,, J. N. Weiser,, S. Johnson,, P. Fontan,, A. Ortqvist,, and H. R. Masure. 1997. Contribution of novel choline-binding proteins to adherence, colonization and immunogenicity of Streptococcus pneumoniae. Mol. Microbiol. 25: 819– 829.

94. Rossjohn, J.,, S. C. Feil,, W. J. McKinstry,, R. K. Tweten,, and M. W. Parker. 1997. Structure of a cholesterol-binding, thiol-activated cytolysin and a model of its membrane form. Cell 89: 685– 692.

95. Roy, S.,, K. Knox,, S. Segal,, D. Griffiths,, C. E. Moore,, K. I. Welsh,, A. Smarason,, N. P. Day,, W. L. McPheat,, D. W. Crook,, and A. V. Hill. 2002. MBL genotype and risk of invasive pneumococcal disease: a case-control study. Lancet 359: 1569– 1573.

96. Rubins, J. B.,, D. Charboneau,, J. C. Paton,, T. J. Mitchell,, P. W. Andrew,, and E. N. Janoff. 1995. Dual function of pneumolysin in the early pathogenesis of murine pneumococcal pneumonia. J. Clin. Invest. 95: 142– 150.

97. Saunders, F. K.,, T. J. Mitchell,, J. A. Walker,, P. W. Andrew,, and G. J. Boulnois. 1989. Pneumolysin, the thiol-activated toxin of Streptococcus pneumoniae, does not require a thiol group for in vitro activity. Infect. Immun. 57: 2547– 2552.

98. Seachrist, J. L.,, and S. S. Ferguson. 2003. Regulation of G protein-coupled receptor endocytosis and trafficking by Rab GTPases. Life Sci. 74: 225– 235.

99. Sebert, M. E.,, L. M. Palmer,, M. Rosenberg,, and J. N. Weiser. 2002. Microarray-based identification of htrA, a Streptococcus pneumoniae gene that is regulated by the Cia-RH two-component system and contributes to nasopharyngeal colonization. Infect. Immun. 70: 4059– 4067.

100. Shaper, M.,, S. K. Hollingshead,, W. H. Benjamin, Jr.,, and D. E. Briles. 2004. PspA protects Streptococcus pneumoniae from killing by apolactoferrin, and antibody to PspA enhances killing of Pneumococci by apolactoferrin. Infect. Immun. 72: 5031– 5040.

101. Smith, T.,, D. Lehmann,, J. Montgomery,, M. Gratten,, I. D. Riley,, and M. P. Alpers. 1993. Acquisition and invasiveness of different serotypes of Streptococcus pneumoniae in young children. Epidemiol. Infect. 111: 27– 39.

102. Spellerberg, B.,, D. R. Cundell,, J. Sandros,, B. J. Pearce,, I. Idanpaan-Heikkila,, C. Rosenow,, and H. R. Masure. 1996. Pyruvate oxidase, as a determinant of virulence in Streptococcus pneumoniae. Mol. Microbiol. 19: 803– 813.

103. Spellerberg, B.,, C. Rosenow,, W. Sha,, and E. I. Tuomanen. 1996. Pneumococcal cell wall activates NF-kappa B in human monocytes: aspects distinct from endotoxin. Microb. Pathog. 20: 309– 317.

104. Stahl, W. L.,, and R. D. O’Toole. 1972. Pneumococcal neuraminidase: purification and properties. Biochim. Biophys. Acta 268: 480– 487.

105. Steinfort, C.,, R. Wilson,, T. Mitchell,, C. Feldman,, A. Rutman,, H. Todd,, D. Sykes,, J. Walker,, K. Saunders,, P. W. Andrew, et al. 1989. Effect of Streptococcus pneumoniae on human respiratory epithelium in vitro. Infect. Immun. 57: 2006– 2013.

106. Stringaris, A. K.,, J. Geisenhainer,, F. Bergmann,, C. Balshusemann,, U. Lee,, G. Zysk,, T. J. Mitchell,, B. U. Keller,, U. Kuhnt,, J. Gerber,, A. Spreer,, M. Bahr,, U. Michel,, and R. Nau. 2002. Neurotoxicity of pneumolysin, a major pneumococcal virulence factor, involves calcium influx and depends on activation of p38 mitogen-activated protein kinase. Neurobiol. Dis. 11: 355– 368.

107. Tettelin, H.,, K. E. Nelson,, I. T. Paulsen,, J. A. Eisen,, T. D. Read,, S. Peterson,, J. Heidelberg,, R. T. DeBoy,, D. H. Haft,, R. J. Dodson,, A. S. Durkin,, M. Gwinn,, J. F. Kolonay,, W. C. Nelson,, J. D. Peterson,, L. A. Umayam,, O. White,, S. L. Salzberg,, M. R. Lewis,, D. Radune,, E. Holtzapple,, H. Khouri,, A. M. Wolf,, T. R. Utterback,, C. L. Hansen,, L. A. McDonald,, T. V. Feldblyum,, S. Angiuoli,, T. Dickinson,, E. K. Hickey,, I. E. Holt,, B. J. Loftus,, F. Yang,, H. O. Smith,, J. C. Venter,, B. A. Dougherty,, D. A. Morrison,, S. K. Hollingshead,, and C. M. Fraser. 2001. Complete genome sequence of a virulent isolate of Streptococcus pneumoniae. Science 293: 498– 506.

108. Tomasz, A.,, and K. Saukkonen. 1989. The nature of cell wall-derived inflammatory components of pneumococci. Pediatr. Infect. Dis. J. 8: 902– 903.

109. Tomasz, A.,, A. Albino,, and E. Zanati. 1970. Multiple antibiotic resistance in a bacterium with suppressed autolytic system. Nature 227: 138– 140.

110. Tong, H. H.,, M. A. McIver,, L. M. Fisher,, and T. F. DeMaria. 1999. Effect of lacto-N-neotetraose, asialoganglioside-GM1 and neuraminidase on adherence of otitis media-associated serotypes of Streptococcus pneumoniae to chinchilla tracheal epithelium. Microb. Pathog. 26: 111– 119.

111. Tong, H. H.,, L. E. Blue,, M. A. James,, and T. F. DeMaria. 2000. Evaluation of the virulence of a Streptococcus pneumoniae neuraminidase-deficient mutant in nasopharyngeal colonization and development of otitis media in the chinchilla model. Infect. Immun. 68: 921– 924.

112. Tong, H. H.,, I. Grants,, X. Liu,, and T. F. DeMaria. 2002. Comparison of alteration of cell surface carbohydrates of the chinchilla tubotympanum and colonial opacity phenotype of Streptococcus pneumoniae during experimental pneumococcal otitis media with or without an antecedent influenza A virus infection. Infect. Immun. 70: 4292– 4301.

113. Torzillo, P. J.,, J. N. Hanna,, F. Morey,, M. Gratten,, J. Dixon,, and J. Erlich. 1995. Invasive pneumococcal disease in central Australia. Med. J. Aust. 162: 182– 186.

114. Tu, A. H.,, R. L. Fulgham,, M. A. McCrory,, D. E. Briles,, and A. J. Szalai. 1999. Pneumococcal surface protein A inhibits complement activation by Streptococcus pneumoniae. Infect. Immun. 67: 4720– 4724.

115. Tuomanen, E. I. 2000. Pathogenesis of pneumococcal inflammation: otitis media. Vaccine 19(Suppl. 1): S38– S40.

116. Tuomanen, E., 2004. Attachment and invasion of the respiratory tract, p. 221– 237. In E. Tuomanen,, T. Mitchell,, D. A. Morrison,, and B. G. Spratt (ed.), The Pneumococcus. ASM Press, Washington, D.C.

117. Tuomanen, E.,, A. Tomasz,, B. Hengstler,, and O. Zak. 1985. The relative role of bacterial cell wall and capsule in the induction of inflammation in pneumococcal meningitis. J. Infect. Dis. 151: 535– 540.

118. Tuomanen, E.,, R. Rich,, and O. Zak. 1987. Induction of pulmonary inflammation by components of the pneumococcal cell surface. Am. Rev. Respir. Dis. 135: 869– 874.

119. Tuomanen, E. I.,, K. Saukkonen,, S. Sande,, C. Cioffe,, and S. D. Wright. 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– 969.

120. Tuomanen, E. I.,, R. Austrian,, and H. R. Masure. 1995. Pathogenesis of pneumococcal infection. N. Engl. J. Med. 332: 1280– 1284.

121. Vollmer, W.,, and A. Tomasz. 2001. Identification of the teichoic acid phosphorylcholine esterase in Streptococcus pneumoniae. Mol. Microbiol. 39: 1610– 1622.

122. Watanabe, T.,, A. Kitani,, P. J. Murray,, and W. Strober. 2004. NOD2 is a negative regulator of Toll-like receptor 2-mediated T helper type 1 responses. Nat. Immunol. 5: 800– 808.

123. Weber, J. R.,, K. Angstwurm,, W. Burger,, K. M. Einhaupl,, and U. Dirnagl. 1995. Anti ICAM-1 (CD 54) monoclonal antibody reduces inflammatory changes in experimental bacterial meningitis. J. Neuroimmunol. 63: 63– 68.

124. Weber, J. R.,, D. Freyer,, C. Alexander,, N. W. Schroder,, A. Reiss,, C. Kuster,, D. Pfeil,, E. I. Tuomanen,, and R. R. Schumann. 2003. Recognition of pneumococcal peptidoglycan: an expanded, pivotal role for LPS binding protein. Immunity 19: 269– 279.

125. Weis, W. I.,, K. Drickamer,, and W. A. Hendrickson. 1992. Structure of a C-type mannose-binding protein complexed with an oligosaccharide. Nature 360: 127– 134.

126. Weiser, J. N.,, R. Austrian,, P. K. Sreenivasan,, and H. R. Masure. 1994. Phase variation in pneumococcal opacity: relationship between colonial morphology and nasopharyngeal colonization. Infect. Immun. 62: 2582– 2589.

127. Weiser, J. N.,, M. Shchepetov,, and S. T. Chong. 1997. Decoration of lipopolysaccharide with phosphorylcholine: a phase-variable characteristic of Haemophilus influenzae. Infect. Immun. 65: 943– 950.

128. Weiser, J. N.,, J. B. Goldberg,, N. Pan,, L. Wilson,, and M. Virji. 1998. The phosphorylcholine epitope undergoes phase variation on a 43-kilodalton protein in Pseudomonas aeruginosa and on pili of Neisseria meningitidis and Neisseria gonorrhoeae. Infect. Immun. 66: 4263– 4267.

129. Weiser, J. N.,, D. Bae,, C. Fasching,, R. W. Scamurra,, A. J. Ratner,, and E. N. Janoff. 2003. Antibody-enhanced pneumococcal adherence requires IgA1 protease. Proc. Natl. Acad. Sci. USA 100: 4215– 4220.

130. Winkelstein, J. A.,, and A. Tomasz. 1978. Activation of the alternative complement pathway by pneumococcal cell wall teichoic acid. J. Immunol. 120: 174– 178.

131. Winter, A. J.,, S. D. Comis,, M. P. Osborne,, M. J. Tarlow,, J. Stephen,, P. W. Andrew,, J. Hill,, and T. J. Mitchell. 1997. A role for pneumolysin but not neuraminidase in the hearing loss and cochlear damage induced by experimental pneumococcal meningitis in guinea pigs. Infect. Immun. 65: 4411– 4418.

132. Zervos, M. J.,, S. Dembinski,, T. Mikesell,, and D. R. Schaberg. 1986. High-level resistance to gentamicin in Streptococcus faecalis: risk factors and evidence for exogenous acquisition of infection. J. Infect. Dis. 153: 1075– 1083.

133. Zhang, J. R.,, K. E. Mostov,, M. E. Lamm,, M. Nanno,, S. Shimida,, M. Ohwaki,, and E. Tuomanen. 2000. The polymeric immunoglobulin receptor translocates pneumococci across human nasopharyngeal epithelial cells. Cell 102: 827– 837.

Tables

Streptococcus pneumoniae: Invasion and Inflammation

/content/10.1128/9781555816513.chap21.tab21-1

TABLE 1

Anatomical site specific-expression of Streptococcus pneumoniae genes as determined by microarray analysis ( 78 ) a

a Bacterial RNA for microarrays was obtained from infected blood of mice (blood), CSF from meningitic rabbits (CSF), and pneumoocci attached to epithelial cells in vitro (ECC)

b Values within shaded boxes indicate genes with decreased transcription.

c Identified by STM ( 47 ).

d Identified by DFI ( 72 ).

e Confirmed by animal infection ( 47 ).

10.1128/9781555816513/tab21-1_thmb.gif

10.1128/9781555816513/tab21-1.gif

TABLE 1

Anatomical site specific-expression of Streptococcus pneumoniae genes as determined by microarray analysis ( 78 ) a

a Bacterial RNA for microarrays was obtained from infected blood of mice (blood), CSF from meningitic rabbits (CSF), and pneumoocci attached to epithelial cells in vitro (ECC)

b Values within shaded boxes indicate genes with decreased transcription.

c Identified by STM ( 47 ).

d Identified by DFI ( 72 ).

e Confirmed by animal infection ( 47 ).