Skip to main content
PMC home page
Journal of Clinical Pathology logoLink to Journal of Clinical Pathology
. 1998 Apr;51(4):270–274. doi: 10.1136/jcp.51.4.270

Application of molecular typing to the epidemiology of Streptococcus pneumoniae.

L M Hall 1
PMCID: PMC500668  PMID: 9659237

Abstract

The spread of antibiotic resistance and the development of new vaccines have focused attention on the epidemiology of Streptococcus pneumoniae over recent years. While serotyping and the determination of antibiotic resistance remain primary methods for characterising pneumococci, molecular typing can add greater discrimination and complementary information. Methods based on restriction fragment length polymorphism within total DNA or non-specific polymerase chain reaction provide information representative of the whole genome and can be used to recognise closely related isolates from different sources, whether in the investigation of possible cross infection at the local level or in the investigation of national or international spread of antibiotic resistant strains. Fingerprinting of penicillin binding protein genes adds further information in the analysis of penicillin resistant isolates. The use of a combination of typing methods to analyse both the genome as a whole and specific loci has led to the realisation that pneumococci undergo horizontal gene transfer much more often than most other bacterial species. In particular the spread of penicillin resistance has been characterised by a combination of the spread of epidemic strains, transfer of chromosomal resistance genes from such strains into other genetic backgrounds, and transfer of capsule genes resulting in the switch of serotypes within strains. In the future molecular typing will have an important role in discovering whether widespread vaccination leads to genetic modification of the pneumococcal population causing invasive disease.

Full text

PDF
273

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adrian P. V., Klugman K. P. Mutations in the dihydrofolate reductase gene of trimethoprim-resistant isolates of Streptococcus pneumoniae. Antimicrob Agents Chemother. 1997 Nov;41(11):2406–2413. doi: 10.1128/aac.41.11.2406. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barnes D. M., Whittier S., Gilligan P. H., Soares S., Tomasz A., Henderson F. W. Transmission of multidrug-resistant serotype 23F Streptococcus pneumoniae in group day care: evidence suggesting capsular transformation of the resistant strain in vivo. J Infect Dis. 1995 Apr;171(4):890–896. doi: 10.1093/infdis/171.4.890. [DOI] [PubMed] [Google Scholar]
  3. Coffey T. J., Berrón S., Daniels M., Garcia-Leoni M. E., Cercenado E., Bouza E., Fenoll A., Spratt B. G. Multiply antibiotic-resistant Streptococcus pneumoniae recovered from Spanish hospitals (1988-1994): novel major clones of serotypes 14, 19F and 15F. Microbiology. 1996 Oct;142(Pt 10):2747–2757. doi: 10.1099/13500872-142-10-2747. [DOI] [PubMed] [Google Scholar]
  4. Coffey T. J., Dowson C. G., Daniels M., Spratt B. G. Genetics and molecular biology of beta-lactam-resistant pneumococci. Microb Drug Resist. 1995 Spring;1(1):29–34. doi: 10.1089/mdr.1995.1.29. [DOI] [PubMed] [Google Scholar]
  5. Coffey T. J., Dowson C. G., Daniels M., Zhou J., Martin C., Spratt B. G., Musser J. M. Horizontal transfer of multiple penicillin-binding protein genes, and capsular biosynthetic genes, in natural populations of Streptococcus pneumoniae. Mol Microbiol. 1991 Sep;5(9):2255–2260. doi: 10.1111/j.1365-2958.1991.tb02155.x. [DOI] [PubMed] [Google Scholar]
  6. Doit C., Denamur E., Picard B., Geslin P., Elion J., Bingen E. Mechanisms of the spread of penicillin resistance in Streptococcus pneumoniae strains causing meningitis in children in France. J Infect Dis. 1996 Sep;174(3):520–528. doi: 10.1093/infdis/174.3.520. [DOI] [PubMed] [Google Scholar]
  7. Dowson C. G., Hutchison A., Brannigan J. A., George R. C., Hansman D., Liñares J., Tomasz A., Smith J. M., Spratt B. G. Horizontal transfer of penicillin-binding protein genes in penicillin-resistant clinical isolates of Streptococcus pneumoniae. Proc Natl Acad Sci U S A. 1989 Nov;86(22):8842–8846. doi: 10.1073/pnas.86.22.8842. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Figueiredo A. M., Austrian R., Urbaskova P., Teixeira L. A., Tomasz A. Novel penicillin-resistant clones of Streptococcus pneumoniae in the Czech Republic and in Slovakia. Microb Drug Resist. 1995 Spring;1(1):71–78. doi: 10.1089/mdr.1995.1.71. [DOI] [PubMed] [Google Scholar]
  9. Gasc A. M., Geslin P., Sicard A. M. Relatedness of penicillin-resistant Streptococcus pneumoniae serogroup 9 strains from France and Spain. Microbiology. 1995 Mar;141(Pt 3):623–627. doi: 10.1099/13500872-141-3-623. [DOI] [PubMed] [Google Scholar]
  10. Hall L. M., Whiley R. A., Duke B., George R. C., Efstratiou A. Genetic relatedness within and between serotypes of Streptococcus pneumoniae from the United Kingdom: analysis of multilocus enzyme electrophoresis, pulsed-field gel electrophoresis, and antimicrobial resistance patterns. J Clin Microbiol. 1996 Apr;34(4):853–859. doi: 10.1128/jcm.34.4.853-859.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Harakeh H., Bosley G. S., Keihlbauch J. A., Fields B. S. Heterogeneity of rRNA gene restriction patterns of multiresistant serotype 6B Streptococcus pneumoniae strains. J Clin Microbiol. 1994 Dec;32(12):3046–3048. doi: 10.1128/jcm.32.12.3046-3048.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hermans P. W., Sluijter M., Elzenaar K., van Veen A., Schonkeren J. J., Nooren F. M., van Leeuwen W. J., de Neeling A. J., van Klingeren B., Verbrugh H. A. Penicillin-resistant Streptococcus pneumoniae in the Netherlands: results of a 1-year molecular epidemiologic survey. J Infect Dis. 1997 Jun;175(6):1413–1422. doi: 10.1086/516474. [DOI] [PubMed] [Google Scholar]
  13. Hermans P. W., Sluijter M., Hoogenboezem T., Heersma H., van Belkum A., de Groot R. Comparative study of five different DNA fingerprint techniques for molecular typing of Streptococcus pneumoniae strains. J Clin Microbiol. 1995 Jun;33(6):1606–1612. doi: 10.1128/jcm.33.6.1606-1612.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kell C. M., Jordens J. Z., Daniels M., Coffey T. J., Bates J., Paul J., Gilks C., Spratt B. G. Molecular epidemiology of penicillin-resistant pneumococci isolated in Nairobi, Kenya. Infect Immun. 1993 Oct;61(10):4382–4391. doi: 10.1128/iai.61.10.4382-4391.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Klugman K. P. Pneumococcal resistance to antibiotics. Clin Microbiol Rev. 1990 Apr;3(2):171–196. doi: 10.1128/cmr.3.2.171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lipsitch M. Vaccination against colonizing bacteria with multiple serotypes. Proc Natl Acad Sci U S A. 1997 Jun 10;94(12):6571–6576. doi: 10.1073/pnas.94.12.6571. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Mandigers C. M., Diepersloot R. J., Dessens M., Mol S. J., van Klingeren B. A hospital outbreak of penicillin-resistant pneumococci in The Netherlands. Eur Respir J. 1994 Sep;7(9):1635–1639. doi: 10.1183/09031936.94.07091635. [DOI] [PubMed] [Google Scholar]
  18. Maskell J. P., Sefton A. M., Hall L. M. Mechanism of sulfonamide resistance in clinical isolates of Streptococcus pneumoniae. Antimicrob Agents Chemother. 1997 Oct;41(10):2121–2126. doi: 10.1128/aac.41.10.2121. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. McDougal L. K., Facklam R., Reeves M., Hunter S., Swenson J. M., Hill B. C., Tenover F. C. Analysis of multiply antimicrobial-resistant isolates of Streptococcus pneumoniae from the United States. Antimicrob Agents Chemother. 1992 Oct;36(10):2176–2184. doi: 10.1128/aac.36.10.2176. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. McDougal L. K., Rasheed J. K., Biddle J. W., Tenover F. C. Identification of multiple clones of extended-spectrum cephalosporin-resistant Streptococcus pneumoniae isolates in the United States. Antimicrob Agents Chemother. 1995 Oct;39(10):2282–2288. doi: 10.1128/aac.39.10.2282. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Millar M. R., Brown N. M., Tobin G. W., Murphy P. J., Windsor A. C., Speller D. C. Outbreak of infection with penicillin-resistant Streptococcus pneumoniae in a hospital for the elderly. J Hosp Infect. 1994 Jun;27(2):99–104. doi: 10.1016/0195-6701(94)90002-7. [DOI] [PubMed] [Google Scholar]
  22. Moissenet D., Valcin M., Marchand V., Garabédian E. N., Geslin P., Garbarg-Chenon A., Vu-Thien H. Molecular epidemiology of Streptococcus pneumoniae with decreased susceptibility to penicillin in a Paris children's hospital. J Clin Microbiol. 1997 Jan;35(1):298–301. doi: 10.1128/jcm.35.1.298-301.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Moore E. P., Williams E. W. Hospital transmission of multiply antibiotic-resistant Streptococcus pneumoniae. J Infect. 1988 Mar;16(2):199–200. doi: 10.1016/s0163-4453(88)94147-3. [DOI] [PubMed] [Google Scholar]
  24. Moreno F., Crisp C., Jorgensen J. H., Patterson J. E. The clinical and molecular epidemiology of bacteremias at a university hospital caused by pneumococci not susceptible to penicillin. J Infect Dis. 1995 Aug;172(2):427–432. doi: 10.1093/infdis/172.2.427. [DOI] [PubMed] [Google Scholar]
  25. Musser J. M., Kroll J. S., Moxon E. R., Selander R. K. Clonal population structure of encapsulated Haemophilus influenzae. Infect Immun. 1988 Aug;56(8):1837–1845. doi: 10.1128/iai.56.8.1837-1845.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Muñoz R., Coffey T. J., Daniels M., Dowson C. G., Laible G., Casal J., Hakenbeck R., Jacobs M., Musser J. M., Spratt B. G. Intercontinental spread of a multiresistant clone of serotype 23F Streptococcus pneumoniae. J Infect Dis. 1991 Aug;164(2):302–306. doi: 10.1093/infdis/164.2.302. [DOI] [PubMed] [Google Scholar]
  27. Pato M. V., Carvalho C. B., Tomasz A. Antibiotic susceptibility of Streptococcus pneumoniae isolates in Portugal. A multicenter study between 1989 and 1993. Microb Drug Resist. 1995 Spring;1(1):59–69. doi: 10.1089/mdr.1995.1.59. [DOI] [PubMed] [Google Scholar]
  28. Raymond J., Bingen E., Brahimi N., Bergeret M., Doit C., Badoual J., Gendrel D. Méningite à la pneumocoque résistant à la pénicilline et transmission nosocomiale en milieu hospitalier pédiatrique confirmée par analyse génomique. Arch Pediatr. 1996 Dec;3(12):1239–1242. doi: 10.1016/s0929-693x(97)85934-9. [DOI] [PubMed] [Google Scholar]
  29. Reichler M. R., Allphin A. A., Breiman R. F., Schreiber J. R., Arnold J. E., McDougal L. K., Facklam R. R., Boxerbaum B., May D., Walton R. O. The spread of multiply resistant Streptococcus pneumoniae at a day care center in Ohio. J Infect Dis. 1992 Dec;166(6):1346–1353. doi: 10.1093/infdis/166.6.1346. [DOI] [PubMed] [Google Scholar]
  30. Reichler M. R., Rakovsky J., Sláciková M., Hlavácová B., Krajcíková L., Tarina P., Sobotová A., Facklam R. R., Breiman R. F. Spread of multidrug-resistant Streptococcus pneumoniae among hospitalized children in Slovakia. J Infect Dis. 1996 Feb;173(2):374–379. doi: 10.1093/infdis/173.2.374. [DOI] [PubMed] [Google Scholar]
  31. Reichmann P., Varon E., Günther E., Reinert R. R., Lüttiken R., Marton A., Geslin P., Wagner J., Hakenbeck R. Penicillin-resistant Streptococcus pneumoniae in Germany: genetic relationship to clones from other European countries. J Med Microbiol. 1995 Nov;43(5):377–385. doi: 10.1099/00222615-43-5-377. [DOI] [PubMed] [Google Scholar]
  32. Robbins J. B., Austrian R., Lee C. J., Rastogi S. C., Schiffman G., Henrichsen J., Mäkelä P. H., Broome C. V., Facklam R. R., Tiesjema R. H. Considerations for formulating the second-generation pneumococcal capsular polysaccharide vaccine with emphasis on the cross-reactive types within groups. J Infect Dis. 1983 Dec;148(6):1136–1159. doi: 10.1093/infdis/148.6.1136. [DOI] [PubMed] [Google Scholar]
  33. Selander R. K., Caugant D. A., Ochman H., Musser J. M., Gilmour M. N., Whittam T. S. Methods of multilocus enzyme electrophoresis for bacterial population genetics and systematics. Appl Environ Microbiol. 1986 May;51(5):873–884. doi: 10.1128/aem.51.5.873-884.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Sibold C., Wang J., Henrichsen J., Hakenbeck R. Genetic relationships of penicillin-susceptible and -resistant Streptococcus pneumoniae strains isolated on different continents. Infect Immun. 1992 Oct;60(10):4119–4126. doi: 10.1128/iai.60.10.4119-4126.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Smith J. M., Smith N. H., O'Rourke M., Spratt B. G. How clonal are bacteria? Proc Natl Acad Sci U S A. 1993 May 15;90(10):4384–4388. doi: 10.1073/pnas.90.10.4384. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Takala A. K., Vuopio-Varkila J., Tarkka E., Leinonen M., Musser J. M. Subtyping of common pediatric pneumococcal serotypes from invasive disease and pharyngeal carriage in Finland. J Infect Dis. 1996 Jan;173(1):128–135. doi: 10.1093/infdis/173.1.128. [DOI] [PubMed] [Google Scholar]
  37. Tenover F. C., Arbeit R. D., Goering R. V., Mickelsen P. A., Murray B. E., Persing D. H., Swaminathan B. Interpreting chromosomal DNA restriction patterns produced by pulsed-field gel electrophoresis: criteria for bacterial strain typing. J Clin Microbiol. 1995 Sep;33(9):2233–2239. doi: 10.1128/jcm.33.9.2233-2239.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Urwin G., Yuan M. F., Hall L. M., Brown K., Efstratiou A., Feldman R. A. Pneumococcal meningitis in the North East Thames Region UK: epidemiology and molecular analysis of isolates. Epidemiol Infect. 1996 Aug;117(1):95–102. doi: 10.1017/s0950268800001175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Versalovic J., Kapur V., Mason E. O., Jr, Shah U., Koeuth T., Lupski J. R., Musser J. M. Penicillin-resistant Streptococcus pneumoniae strains recovered in Houston: identification and molecular characterization of multiple clones. J Infect Dis. 1993 Apr;167(4):850–856. doi: 10.1093/infdis/167.4.850. [DOI] [PubMed] [Google Scholar]
  40. van Belkum A., Sluijuter M., de Groot R., Verbrugh H., Hermans P. W. Novel BOX repeat PCR assay for high-resolution typing of Streptococcus pneumoniae strains. J Clin Microbiol. 1996 May;34(5):1176–1179. doi: 10.1128/jcm.34.5.1176-1179.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Pathology are provided here courtesy of BMJ Publishing Group

RESOURCES