1887

Abstract

Capsule phase variants were isolated from serotype 8 and serotype 37 pneumococcal sorbarods. Sequence duplications within the essential capsule genes – (type 8) and (type 37) – were found to introduce frameshifts and generate acapsular phenotypes. Capsular revertants possessed wild-type and genes, indicating the precise excision of these duplications. Reversion frequencies (OFF–ON) fit a linear relationship between log(frequency of reversion) and log(length of duplication), previously found for serotype three pneumococci [ Waite, R. D., Struthers, J. K. & Dowson, C. G. (2001) . 42, 1223–1232]. This study provides evidence that capsule phase variation can occur in pneumococcal serotypes with either simple (one to three genes) or complex capsule-encoding loci (12 genes). Given the key role of CapE (the first monosaccharide transferase) in other clinically important pneumococci, such as serotypes 14 and 19F with complex capsular loci, the observed duplication within suggests that capsule phase variation could be controlled by tandem sequence duplication in homologues in other pneumococcal serotypes that construct their capsules through polymerization of lipid-linked intermediates.

Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.26011-0
2003-02-01
2020-01-26
Loading full text...

Full text loading...

/deliver/fulltext/micro/149/2/mic149497.html?itemId=/content/journal/micro/10.1099/mic.0.26011-0&mimeType=html&fmt=ahah

References

  1. Adamou J. E, Wizemann T. M, Barren P., Langermann S. 1998; Adherence of Streptococcus pneumoniae to human bronchial epithelial cells (BEAS-2B). Infect Immun66:820–822
    [Google Scholar]
  2. Appelbaum P. C, Gladkova C, Hryniewicz W.. 10 other authors 1996; Carriage of antibiotic-resistant Streptococcus pneumoniae by children in eastern and central Europe – a multicenter study with use of standardized methods. Clin Infect Dis23:712–717
    [Google Scholar]
  3. Arrecubieta C, Lopez R., Garcia E. 1996; Type 3-specific synthase of Streptococcus pneumoniae (Cap3B) directs type 3 polysaccharide biosynthesis in Escherichia coli and in pneumococcal strains of different serotypes. J Exp Med184:449–455
    [Google Scholar]
  4. Austrian R. 1986; Some aspects of the pneumococcal carrier state. J Antimicrob Chemother18:35–45
    [Google Scholar]
  5. Butler J. C, Dowell S. F., Breiman R. F. 1998; Epidemiology of emerging pneumococcal drug resistance: implications for treatment and prevention. Vaccine16:1693–1697
    [Google Scholar]
  6. Dillard J. P, Vandersea M. W., Yother J. 1995; Characterisation of the cassette containing genes for type 3 capsular polysaccharide biosynthesis in Streptococcus pneumoniae. J Exp Med181:973–983
    [Google Scholar]
  7. Ertugrul N, Rodriguez-Barradas M. C, Musher D. M, Ryan M. A, Agin C. S, Murphy S. J, Shayegani M., Watson D. A. 1997; BOX-polymerase chain reaction-based DNA analysis of non-serotypeable Streptococcus pneumoniae implicated in outbreaks of conjunctivitis. J Infect Dis176:1401–1405
    [Google Scholar]
  8. Guidolin A, Morona J. K, Morona R, Hansman D., Paton J. C. 1994; Nucleotide sequence analysis of genes essential for capsular polysaccharide biosynthesis in Streptococcus pneumoniae type 19F. Infect Immun62:5384–5396
    [Google Scholar]
  9. Hammerschmidt S, Hilse R, van Putten J. P, Gerardy-Schahn R, Unkmeir A., Frosch M. 1996a; Modulation of cell surface sialic acid expression in Neisseria meningitidis via a transposable genetic element. EMBO J15:192–198
    [Google Scholar]
  10. Hammerschmidt S, Muller A, Sillmann H.. 7 other authors 1996b; Capsule phase variation in Neisseria meningitidis serogroup B by slipped-strand mispairing in the polysialyltransferase gene ( siaD ): correlation with bacterial invasion and the outbreak of meningococcal disease. Mol Microbiol20:1211–1220
    [Google Scholar]
  11. Henrichsen J. 1995; Six newly recognized types of Streptococcus pneumoniae. J Clin Microbiol33:2759–2762
    [Google Scholar]
  12. Iannelli F, Pearce B. J., Pozzi G. 1999; The type 2 capsule locus of Streptococcus pneumoniae. J Bacteriol181:2652–2654
    [Google Scholar]
  13. Jiang S. M, Wang L., Reeves P. R. 2001; Molecular characterisation of Streptococcus pneumoniae type 4, 6B, 8, and 18C capsular polysaccharide gene clusters. Infect Immun69:1244–1255
    [Google Scholar]
  14. Keck T, Leiacker R, Riechelmann H., Rettinger G. 2000; Temperature profile in the nasal cavity. Laryngoscope110:651–654
    [Google Scholar]
  15. Kim J. O., Weiser J. N. 1998; Association of intrastrain phase variation in quantity of capsular polysaccharide and teichoic acid with the virulence of Streptococcus pneumoniae. J Infect Dis177:368–377
    [Google Scholar]
  16. Koeuth T, Versalovic J., Lupski J. R. 1995; Differential subsequence conservation of interspersed repetitive Streptococcus pneumoniae Box elements in diverse bacteria. Genome Res5:408–418
    [Google Scholar]
  17. Kolkman M. A, Morrison D. A, Van Der Zeijst B. A., Nuijten P. J. 1996; The capsule polysaccharide synthesis locus of Streptococcus pneumoniae serotype 14: identification of the glycosyl transferase gene cps14E. J Bacteriol178:3736–3741
    [Google Scholar]
  18. Kolkman M. A, Wakarchuk W, Nuijten P. J., van der Zeijst B. A. 1997a; Capsular polysaccharide synthesis in Streptococcus pneumoniae serotype 14: molecular analysis of the complete cps locus and identification of genes encoding glycosyltransferases required for the biosynthesis of the tetrasaccharide subunit. Mol Microbiol26:197–208
    [Google Scholar]
  19. Kolkman M. A, van der Zeijst B. A., Nuijten P. J. 1997b; Functional analysis of glycosyltransferases encoded by the capsular polysaccharide biosynthesis locus of Streptococcus pneumoniae serotype 14. J Biol Chem272:19502–19508
    [Google Scholar]
  20. Kolkman M. A, van der Zeijst B. A., Nuijten P. J. 1998; Diversity of capsular polysaccharide synthesis gene clusters in Streptococcus pneumoniae. J Biochem (Tokyo)123:937–945
    [Google Scholar]
  21. Llull D, Lopez R, Garcia E., Munoz R. 1998; Molecular structure of the gene cluster responsible for the synthesis of the polysaccharide capsule of Streptococcus pneumoniae type 33F. Biochim Biophys Acta 1443;217–224
    [Google Scholar]
  22. Llull D, Munoz R, Lopez R., Garcia E. 1999; A single gene ( tts ) located outside the cap locus directs the formation of Streptococcus pneumoniae type 37 capsular polysaccharide. Type 37 pneumococci are natural, genetically binary strains. J Exp Med190:241–251
    [Google Scholar]
  23. Llull D, Lopez R., Garcia E. 2000; Clonal origin of the type 37 Streptococcus pneumoniae. Microb Drug Resist6:269–275
    [Google Scholar]
  24. Llull D, Garcia E., Lopez R. 2001; Tts, a processive beta-glucosyltransferase of Streptococcus pneumoniae , directs the synthesis of the branched type 37 capsular polysaccharide in pneumococcus and other gram-positive species. J Biol Chem276:21053–21061
    [Google Scholar]
  25. Magee A. D., Yother J. 2001; Requirement for capsule in colonization by Streptococcus pneumoniae. Infect Immun69:3755–3761
    [Google Scholar]
  26. Morona J. K, Morona R., Paton J. C. 1997a; Characterization of the locus encoding the Streptococcus pneumoniae type 19F capsular polysaccharide biosynthetic pathway. Mol Microbiol23:751–763
    [Google Scholar]
  27. Morona J. K, Morona R., Paton J. C. 1997b; Molecular and genetic characterization of the capsule biosynthesis locus of Streptococcus pneumoniae type 19B. J Bacteriol179:4953–4958
    [Google Scholar]
  28. Morona J. K, Morona R., Paton J. C. 1999; Analysis of the 5′ portion of the type 19A capsule locus identifies two classes of cpsC , cpsD , and cpsE genes in Streptococcus pneumoniae. J Bacteriol181:3599–3605
    [Google Scholar]
  29. Morona J. K, Paton J. C, Miller D. C., Morona R. 2000; Tyrosine phosphorylation of CpsD negatively regulates capsular polysaccharide biosynthesis in Streptococcus pneumoniae. Mol Microbiol35:1431–1442
    [Google Scholar]
  30. Moxon E. R., Kroll J. S. 1990; The role of bacterial polysaccharide capsules as virulence factors. Curr Top Microbiol Immunol150:65–85
    [Google Scholar]
  31. Muller-Graf C. D, Whatmore A. M, King S. J.. 7 other authors 1999; Population biology of Streptococcus pneumoniae isolated from oropharyngeal carriage and invasive disease. Microbiology145:3283–3293
    [Google Scholar]
  32. Munoz R, Mollerach M, Lopez R., Garcia E. 1997; Molecular organisation of the genes required for the synthesis of type 1 capsular polysaccharide of Streptococcus pneumoniae : formation of binary encapsulated pneumococci and identification of cryptic dTDP-rhamnose biosynthesis genes. Mol Microbiol25:79–92
    [Google Scholar]
  33. Munoz R, Mollerach M, Lopez R., Garcia E. 1999; Characterisation of the type 8 capsular gene cluster of Streptococcus pneumoniae. J Bacteriol181:6214–6219
    [Google Scholar]
  34. Musher D. M. 1992; Infections caused by Streptococcus pneumoniae : clinical spectrum, pathogenesis, immunity, and treatment. Clin Infect Dis14:801–807
    [Google Scholar]
  35. Musher D. M, Dowell M. E, Shortridge V. D, Flamm R. K, Jorgensen J. H, Le Magueres P., Krause K. L. 2002; Emergence of macrolide resistance during treatment of pneumococcal pneumonia. N Engl J Med346:631–632
    [Google Scholar]
  36. Paton J. C, Andrew P. W, Boulnois G. J., Mitchell T. J. 1993; Molecular analysis of the pathogenicity of Streptococcus pneumoniae : the role of pneumococcal proteins. Annu Rev Microbiol47:89–115
    [Google Scholar]
  37. Ramirez M., Tomasz A. 1998; Molecular characterisation of the complete 23F capsular polysaccharide locus of Streptococcus pneumoniae. J Bacteriol180:5273–5278
    [Google Scholar]
  38. Ring A., Tuomanen E. 2000; Host cell invasion by Streptococcus pneumoniae. Subcell Biochem33:125–135
    [Google Scholar]
  39. Ring A, Weiser J. N., Tuomanen E. I. 1998; Pneumococcal trafficking across the blood–brain barrier. Molecular analysis of a novel bidirectional pathway. J Clin Invest102:347–360
    [Google Scholar]
  40. Saluja S. K., Weiser J. N. 1995; The genetic basis of colony opacity in Streptococcus pneumoniae : evidence for the effect of box elements on the frequency of phenotypic variation. Mol Microbiol16:215–227
    [Google Scholar]
  41. Sung R. Y. T, Ling J. M, Fung S. M, Oppenheimer S. J, Crook D. W, Lau J. T. F., Cheng A. F. B. 1995; Carriage of Haemophilus influenzae and Streptococcus pneumoniae in healthy Chinese and Vietnamese children in Hong Kong. Acta Paediatr84:1262–1267
    [Google Scholar]
  42. Talbot U. M, Paton A. W., Paton J. C. 1996; Uptake of Streptococcus pneumoniae by respiratory epithelial cells. Infect Immun64:3772–3777
    [Google Scholar]
  43. Throup J. P, Koretke K. K, Bryant A. P.. 9 other authors 2000; A genomic analysis of two-component signal transduction in Streptococcus pneumoniae. Mol Microbiol35:566–576
    [Google Scholar]
  44. van Dam J. E, Fleer A., Snippe H. 1990; Immunogenicity and immunochemistry of Streptococcus pneumoniae capsular polysaccharides. Antonie Leeuwenhoek58:1–47
    [Google Scholar]
  45. Waite R. D, Struthers J. K., Dowson C. G. 2001; Spontaneous sequence duplication within an open reading frame of the pneumococcal type 3 capsule locus causes high-frequency phase variation. Mol Microbiol42:1223–1232
    [Google Scholar]
  46. Watson D. A., Musher D. M. 1990; Interruption of capsule production in Streptococcus pneumoniae serotype 3 by insertion of transposon Tn 916. Infect Immun. 583135–3138
  47. Whatmore A. M, King S. J, Doherty N. C, Sturgeon D, Chanter N., Dowson C. G. 1999; Molecular characterisation of equine isolates of Streptococcus pneumoniae : natural disruption of genes encoding the virulence factors pneumolysin and autolysin. Infect Immun67:2776–2782
    [Google Scholar]
  48. World Health Organization 1999; Pneumococcal vaccines. Wkly Epidemiol Rec74:177–184
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.26011-0
Loading
/content/journal/micro/10.1099/mic.0.26011-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error