Chapter 21 : Streptococcus pneumoniae: Invasion and Inflammation

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(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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Image of FIGURE 1

() 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.)

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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Image of FIGURE 2

(A) Graphical representation of the CBP LytA ( ). 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 ( ).

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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Image of 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 .)

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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Image of 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: -acetylgalactosamine; Galn: galactosamine; L-Ala: -alanine; D-Glu: -glucose; L-Lys: -lysine; TNF: tumor necrosis factor; NO: nitric oxide; PGE: prostaglandin E2; IC: intracranial.

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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Image of 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 and .)

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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Image of 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 .)

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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Generic image for table

Anatomical site specific-expression of genes as determined by microarray analysis ( )

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)

Values within shaded boxes indicate genes with decreased transcription.

Identified by STM ( ).

Identified by DFI ( ).

Confirmed by animal 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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