Chapter 25 : Vaccine-Induced Immunity to Pneumococcal Infection

[chapter 2] Venn diagrams of BlastP comparisons of different genomes. The genomes compared in panel A are S. pneumoniae strain TIGR4, S. agalactiae strain 2603 V/R (GBS), and S. pyogenes strain SF370 (GAS). Numbers in the intersections represent genes shared in the respective species-to-species (A) or S. pneumoniae strain-to-strain (B) comparison. The colors represent the genome used as the query in each case. Numbers vary slightly depending on the query because of gene duplications in some strains or species. A BlastP e-value cutoff of 10e−15 was used in each case.

[chapter 2] Circular representation of the genomic content of 13 diverse strains compared to the TIGR4 strain genome through CGH on a preliminary microarray. The cDNA microarray consisted of amplicons representing 1,954 of the 2,326 genes from the sequenced strain TIGR4. Results for the competitive hybridization between TIGR4 DNA labeled with Cy3 and the DNA from a single strain labeled with Cy5 are shown in each of the circles. Genes are either (i) present in test strain (white), (ii) absent from test strain (shown in blue for Cy3/Cy5 ratios of 5 to 10 or red for Cy3/Cy5 ratios of more than 10), or (iii) not present on the array and not analyzed (182 genes, 8% of total) (also left in white, so as to focus the discussion on those genes for which a test was performed but no orthologs were detected). The two outermost circles are the predicted genes on the forward and reverse strands, color coded by functional category. The third circle is the analysis; of atypical nucleotide composition; the most atypical regions are displayed in green. The fourth circle is the GC skew analysis; positive values are indicated in yellow, and negative values are in cyan. The next circles on the left diagram correspond to strains MA through MG (outer circle to inner circle). The circles on the right diagram correspond to strains MI through MN.

[chapter 5] Structural model of PLY showing the four domains of the proteins and the conserved undecapeptide loop. The region involved in complement activation is marked. The model is based on reference 74.

[chapter 6] Predicted structural organization of LytA and its Ch-binding domain. (A) Physicochemical studies suggest the organization of a LytA dimer having four subdomains per monomer, two (N1 and N2) located N terminally and two (C1 and C2) located C terminally. Reprinted from the Journal of Biological Chemistry (69) with permission of the publisher. (B) Stereo ribbon diagram of the dimeric C-LytA with β-strand assignments. The two monomers are differently colored (yellow and cyan). Reprinted from the Journal of Molecular Biology (14) with permission of the publisher. (C) Ch-binding sites. a, ribbon diagram of the C-LytA dimer inscribed into the molecular surface. b, stereo diagram of one Ch-binding site where choline is highlighted in orange. Reprinted from Nature Structural Biology (15) with permission of the publisher.

[chapter 8] Clonal complexes within the pneumococcal population represented in the MLST database. All isolates in the pneumococcal MLST database (as of September 2003) were displayed as a single eBURST diagram (a population snapshot [17a]). Clusters of linked STs correspond to clonal complexes; single STs differ from all other STs in the population at two or more loci. The areas of the circles representing the individual STs indicate the prevalence of each ST in the current database; STs in blue are the predicted founders of the clonal complex, and those in yellow are founders of subgroups within the clonal complex (17a). For clarity, ST numbers are not shown, except for ST81.

[chapter 15] Progression of pneumonia followed by in vivo imaging. Xenogen Imaging System was used to follow the spread of luciferase-bearing pneumococci introduced intranasally. Bacteria descended into the lung by 24 h, spread from one lung to the other by 48 h, and then spread to the bloodstream by 72 h.

[chapter 15] Histopathology of three stages of consolidation. Hematoxylin and eosin staining of sections of lung representing the indicated stages of consolidation progressing from engorgement to red to grey hepatization. (Images courtesy of S. Dixon, St. Jude Children's Research Hospital.)

[chapter 15] Model of pneumococcal invasion into alveolar epithelial cells. Pneumococci adhere to glycoconjugates on the surfaces of epithelial cells. A second step is required to initiate uptake and transcytosis. In the lung, the second step involves the interaction of choline on the cell wall and CbpA with PAFr. The molecular details of this event are as yet unclear but pneumococci and PAFr colocalize during invasion of type II alveolar cells in vitro. Subsequent to PAFr ligation, bacteria are taken up into a clathrin-coated vesicle that recruits the cytosolic scaffold protein β arrestin. The vesicle then moves across the cell from the apical to basolateral surface. Internalized bacteria do not escape the vesicles. In vitro, bilayers of epithelial and endothelial cells can be crossed by pneumococci in about 9 h.

[chapter 16] Gram stain of CSF from a patient with meningitis. A large number of leukocytes surrounded by gram-positive diplococci have accumulated in the fluid. Note that in the fluid environment, few bacteria are effectively phagocytosed. (Photo courtesy of E. Halle, Charité Hospital, Berlin, Germany.)

[chapter 18] (a) Antibiotic consumption among the Jewish and Bedouin children <5 years of age in southern Israel, expressed by prescription per 1,000 individuals per year. The data for the Jewish children include all prescriptions in the city of Beer-Sheva for the largest health maintenance organization covering approximately 60% of all children; for the Bedouin children, the data are derived from all prescriptions for the two largest pediatric primary care centers. (b) Proportion of all penicillin-nonsusceptible (Pen-R) S. pneumoniae middle ear fluid isolated obtained during the years 1998 to 2002 (from children with acute otitis media) that were dually resistant to penicillin and macrolides. (c) Actual and predicted proportions of resistance among invasive S. pneumoniae isolates derived from population-based surveillance in eight sites around the United States covering approximately 21 million people (81). The symbols represent the actual proportions of strains resistant to both erythromycin and penicillin (●), penicillin only (▄), and erythromycin only (▲). These lines represent the predicted proportions of strains resistant to both erythromycin and penicillin (solid), penicillin alone (dashed) and erythromycin only (dotted).