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Microbiology and pathogenesis of Streptococcus pneumoniae

Elaine I Tuomanen, MD
Section Editors
Daniel J Sexton, MD
Sheldon L Kaplan, MD
Deputy Editor
Sheila Bond, MD


Streptococcus pneumoniae occupies an important position in the history of microbiology:

The organism was first identified in 1881.

Its role in causing lobar pneumonia was appreciated by the late 1880s.

The central role of antibody in host defense against extracellular organisms was first described for the pneumococcus.

The first recognition that antibody directed to the capsular polysaccharide of a bacteria could be protective was shown for the pneumococcus; this observation forms the basis for many current bacterial vaccines.

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Literature review current through: Nov 2017. | This topic last updated: Aug 10, 2017.
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  1. Tomasz A, Albino A, Zanati E. Multiple antibiotic resistance in a bacterium with suppressed autolytic system. Nature 1970; 227:138.
  2. Tettelin H, Nelson KE, Paulsen IT, et al. Complete genome sequence of a virulent isolate of Streptococcus pneumoniae. Science 2001; 293:498.
  3. Hoskins J, Alborn WE Jr, Arnold J, et al. Genome of the bacterium Streptococcus pneumoniae strain R6. J Bacteriol 2001; 183:5709.
  4. Obert C, Sublett J, Kaushal D, et al. Identification of a Candidate Streptococcus pneumoniae core genome and regions of diversity correlated with invasive pneumococcal disease. Infect Immun 2006; 74:4766.
  5. Blomberg C, Dagerhamn J, Dahlberg S, et al. Pattern of accessory regions and invasive disease potential in Streptococcus pneumoniae. J Infect Dis 2009; 199:1032.
  6. Musher DM, Rueda AM, Kaka AS, Mapara SM. The association between pneumococcal pneumonia and acute cardiac events. Clin Infect Dis 2007; 45:158.
  7. Brown AO, Mann B, Gao G, et al. Streptococcus pneumoniae translocates into the myocardium and forms unique microlesions that disrupt cardiac function. PLoS Pathog 2014; 10:e1004383.
  8. Brown AO, Millett ER, Quint JK, Orihuela CJ. Cardiotoxicity during invasive pneumococcal disease. Am J Respir Crit Care Med 2015; 191:739.
  9. Caimano MJ, Hardy GG, Yother J. Capsule genetics in Streptococcus pneumoniae and a possible role for transposition in the generation of the type 3 locus. Microb Drug Resist 1998; 4:11.
  10. Mollerach M, López R, García E. Characterization of the galU gene of Streptococcus pneumoniae encoding a uridine diphosphoglucose pyrophosphorylase: a gene essential for capsular polysaccharide biosynthesis. J Exp Med 1998; 188:2047.
  11. Kietzman CC, Gao G, Mann B, et al. Dynamic capsule restructuring by the main pneumococcal autolysin LytA in response to the epithelium. Nat Commun 2016; 7:10859.
  12. Barocchi MA, Ries J, Zogaj X, et al. A pneumococcal pilus influences virulence and host inflammatory responses. Proc Natl Acad Sci U S A 2006; 103:2857.
  13. Cundell D, Masure HR, Tuomanen EI. The molecular basis of pneumococcal infection: a hypothesis. Clin Infect Dis 1995; 21 Suppl 3:S204.
  14. Tuomanen EI, Austrian R, Masure HR. Pathogenesis of pneumococcal infection. N Engl J Med 1995; 332:1280.
  15. Idänpään-Heikkilä I, Simon PM, Zopf D, et al. Oligosaccharides interfere with the establishment and progression of experimental pneumococcal pneumonia. J Infect Dis 1997; 176:704.
  16. McCullers JA, Rehg JE. Lethal synergism between influenza virus and Streptococcus pneumoniae: characterization of a mouse model and the role of platelet-activating factor receptor. J Infect Dis 2002; 186:341.
  17. McCullers JA, Bartmess KC. Role of neuraminidase in lethal synergism between influenza virus and Streptococcus pneumoniae. J Infect Dis 2003; 187:1000.
  18. Oggioni MR, Trappetti C, Kadioglu A, et al. Switch from planktonic to sessile life: a major event in pneumococcal pathogenesis. Mol Microbiol 2006; 61:1196.
  19. Ring A, Weiser JN, Tuomanen EI. Pneumococcal trafficking across the blood-brain barrier. Molecular analysis of a novel bidirectional pathway. J Clin Invest 1998; 102:347.
  20. Brueggemann AB, Peto TE, Crook DW, et al. Temporal and geographic stability of the serogroup-specific invasive disease potential of Streptococcus pneumoniae in children. J Infect Dis 2004; 190:1203.
  21. Cundell DR, Gerard NP, Gerard C, et al. Streptococcus pneumoniae anchor to activated human cells by the receptor for platelet-activating factor. Nature 1995; 377:435.
  22. Loh LN, Gao G, Tuomanen EI. Dissecting Bacterial Cell Wall Entry and Signaling in Eukaryotic Cells: an Actin-Dependent Pathway Parallels Platelet-Activating Factor Receptor-Mediated Endocytosis. MBio 2017; 8.
  23. Miller ML, Gao G, Pestina T, et al. Hypersusceptibility to invasive pneumococcal infection in experimental sickle cell disease involves platelet-activating factor receptor. J Infect Dis 2007; 195:581.
  24. Håkansson A, Kidd A, Wadell G, et al. Adenovirus infection enhances in vitro adherence of Streptococcus pneumoniae. Infect Immun 1994; 62:2707.
  25. Tuomanen E. The Pneumococcus, ASM Press, Washington, DC 2004.
  26. Weiser JN, Pan N, McGowan KL, et al. 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 1998; 187:631.
  27. Kwon HY, Ogunniyi AD, Choi MH, et al. The ClpP protease of Streptococcus pneumoniae modulates virulence gene expression and protects against fatal pneumococcal challenge. Infect Immun 2004; 72:5646.
  28. Tomasz A. Control of the competent state in Pneumococcus by a hormone-like cell product: an example for a new type of regulatory mechanism in bacteria. Nature 1965; 208:155.
  29. Mitchell TJ, Andrew PW. Biological properties of pneumolysin. Microb Drug Resist 1997; 3:19.
  30. Rubins JB, Charboneau D, Paton JC, et al. Dual function of pneumolysin in the early pathogenesis of murine pneumococcal pneumonia. J Clin Invest 1995; 95:142.
  31. Braun JS, Sublett JE, Freyer D, et al. Pneumococcal pneumolysin and H(2)O(2) mediate brain cell apoptosis during meningitis. J Clin Invest 2002; 109:19.
  32. Tuomanen E, Pollack H, Parkinson A, et al. Microbiological and clinical significance of a new property of defective lysis in clinical strains of pneumococci. J Infect Dis 1988; 158:36.
  33. Weber JR, Freyer D, Alexander C, et al. Recognition of pneumococcal peptidoglycan: an expanded, pivotal role for LPS binding protein. Immunity 2003; 19:269.
  34. Yoshimura A, Lien E, Ingalls RR, et al. Cutting edge: recognition of Gram-positive bacterial cell wall components by the innate immune system occurs via Toll-like receptor 2. J Immunol 1999; 163:1.
  35. Girardin SE, Sansonetti PJ, Philpott DJ. Intracellular vs extracellular recognition of pathogens--common concepts in mammals and flies. Trends Microbiol 2002; 10:193.
  36. Girardin SE, Travassos LH, Hervé M, et al. Peptidoglycan molecular requirements allowing detection by Nod1 and Nod2. J Biol Chem 2003; 278:41702.
  37. Pauleau AL, Murray PJ. Role of nod2 in the response of macrophages to toll-like receptor agonists. Mol Cell Biol 2003; 23:7531.
  38. Tuomanen EI, Masure HR. Molecular and cellular biology of pneumococcal infection. Microb Drug Resist 1997; 3:297.
  39. Bullard DC, Qin L, Lorenzo I, et al. P-selectin/ICAM-1 double mutant mice: acute emigration of neutrophils into the peritoneum is completely absent but is normal into pulmonary alveoli. J Clin Invest 1995; 95:1782.
  40. Doerschuk CM, Winn RK, Coxson HO, Harlan JM. CD18-dependent and -independent mechanisms of neutrophil emigration in the pulmonary and systemic microcirculation of rabbits. J Immunol 1990; 144:2327.
  41. Tuomanen E, Tomasz A, Hengstler B, Zak O. The relative role of bacterial cell wall and capsule in the induction of inflammation in pneumococcal meningitis. J Infect Dis 1985; 151:535.
  42. Täuber MG, Doroshow CA, Hackbarth CJ, et al. Antibacterial activity of beta-lactam antibiotics in experimental meningitis due to Streptococcus pneumoniae. J Infect Dis 1984; 149:568.
  43. Tuomanen EI, Saukkonen K, Sande S, et al. 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 1989; 170:959.
  44. Braun JS, Novak R, Herzog KH, et al. Neuroprotection by a caspase inhibitor in acute bacterial meningitis. Nat Med 1999; 5:298.
  45. Braun JS, Novak R, Murray PJ, et al. Apoptosis-inducing factor mediates microglial and neuronal apoptosis caused by pneumococcus. J Infect Dis 2001; 184:1300.
  46. Zweigner J, Jackowski S, Smith SH, et al. Bacterial inhibition of phosphatidylcholine synthesis triggers apoptosis in the brain. J Exp Med 2004; 200:99.