Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Transposable multiple antibiotic resistance in Streptococcus pneumoniae


A mobile genetic element, designated Tn1545, was detected in the chromosome of Streptococcus pneumoniae BM4200, a clinical isolate multiply resistant to antibiotics. The 25.3 kb element conferred resistance to kanamycin and structurally related aminoglycosides by synthesis of a 3′-aminoglycoside phosphotranferase type III (aphA-3), to macrolide-lincosamide-streptogramin B-type antibiotics (ermAM), and to tetracycline (tetM). Tn1545 was self-transferable to a recombination deficient S. faecalis strain where it was able to transpose to various sites, induce insertional mutations and was apparently cleanly excised. The element also conjugated to and transposed to the chromosome of S. faecalis, S. lactis, S. diacetylactis, S. cremoris, S. sanguis, Staphylococcus aureus, and Listeria monocytogenes. The properties of the conjugative transposon Tn1545 could account for the sudden emergence, rapid dissemination, and stabilisation of multiple resistance to antibiotics in S. pneumoniae in the absence of plasmids.

This is a preview of subscription content, log in to check access.


  1. Borderon E, Bieth G, Horodniceanu T (1982) Genetic and physical studies of Streptococcus faecalis hemolysin plasmids. FEMS Microbiol Lett 14:51–55

  2. Boyer HW, Roulland-Dussoix D (1969) A complementation analysis of the restriction and modification of DNA in Escherichia coli. J Mol Biol 41:459–472

  3. Burdett V, Inamine J, Rajagopalan S (1982) Multiple tetracycline resistance determinants in Streptococcus. In: Schlessinger D (ed) Microbiology-1982. American Society for Microbiology, Washington DC, pp 155–158

  4. Buu-Hoï A, Horodniceanu T (1980) Conjugative transfer of multiple antibiotic resistance markers in Streptococcus pneumoniae. J Bacteriol 143:313–320

  5. Carlier C, Courvalin P (1982a) Resistance of streptococci to aminoglycoside-aminocyclitol antibiotics. In: Schlessinger D (ed) Microbiology-1982. American Society for Microbiology, Washington DC, pp 162–166

  6. Carlier C, Courvalin P (1982b) A plasmid which does not encode the aminoglycoside phosphotransferase in the butirosin-producing strain of Bacillus circulans. J Antibiot 35:629–634

  7. Clewell DB (1981) Plasmids drug resistance, and gene transfer in the genus Streptococcus. Microbiol Rev 45:409–436

  8. Collatz E, Carlier C, Courvalin P (1983) The chromosomal 3′5″-aminoglycoside phosphotransferase in Streptococcus pneumoniae is closely related to its plasmid-coded homologues in Streptococcus faecalis and Staphylococcus aureus. J Bacteriol 156:1373–1377

  9. Collatz E, Carlier C, Courvalin P (1984) Characterization of highlevel aminoglycoside resistance in a strain of Streptococcus pneumoniae. J Gen Microbiol 130:1665–1671

  10. Courvalin P, Carlier C (1987) Tn1545: A conjugative shuttle transposon. Mol Gen Genet (in press)

  11. Courvalin P, Davies J (1977) Plasmid-mediated aminoglycoside phosphotransferase of broad substrate range that phosphorylates amikacin. Antimicrob Agents Chemother 11:619–624

  12. Courvalin P, Fiandt M (1980) Aminoglycoside-modifying enzymes of Staphylococcus aureus: expression in Escherichia coli. Gene 9:247–269

  13. Courvalin PM, Carlier C, Chabbert YA (1972) Plasmid-linked tetracycline and erythromycin resistance in group D “Streptococcus”. Ann Inst Pasteur (Paris) 123:755–759

  14. Courvalin PM, Shaw WV, Jacob AE (1978) Plasmid-mediated mechanisms of resistance to aminoglycoside antibiotics and to chloramphenicol in group D streptococci. Antimicrob Agents Chemother 13:716–725

  15. Courvalin P, Carlier C, Collatz E (1979) Structural and functional relationships between plasmid-mediated aminocyclitol-modifying enzymes from Gram-positive and Gram-negative bacteria. Program abstract no. 85, 11th Lunteren Lecture, Lunteren, The Netherlands

  16. Courvalin P, Carlier C, Collatz E (1980) Plasmid-mediated resistance to aminocyclitol antibiotics in group D streptococci. J Bacteriol 143:541–551

  17. Cross-Belard M, Oudet P, Chambon P (1973) Isolation of high molecular weight DNA from mammalian cells. Eur J Biochem 36:32–38

  18. Denhardt DT (1966) A membrane filter technique for the detection of complementary DNA. Biochem Biophys Res Commun 23:641–646

  19. Engel HWB, Soedirman N, Rost JA, van Leeuwen WJ, van Embden JDA (1980) Transferability of macrolide, lincomycin, and streptogramin resistances between group A, B, and D streptococci. Streptococcus pneumoniae, and Staphylococcus aureus. J Bacteriol 142:407–413

  20. Fitzgerald GF, Clewell DB (1985) A conjugative transposon (Tn919) in Streptococcus sanguis. Infect Immun 47:415–420

  21. Franke AE, Clewell DB (1981) Evidence for a chromosome-borne resistance transposon (Tn916) in Streptococcus faecalis that is capable of “conjugal” tranfer in the absence of a conjugative plasmid. J Bacteriol 145:494–502

  22. Gaillard JL, Berche P, Sansonetti P (1986) Transposon mutagenesis as a tool to study the role of hemolysin in the virulence of Listeria monocytogenes. Infect Immun 52:50–55

  23. Gawron-Burke C, Clewell DB (1984) Regeneration of insertionally inactivated streptococcal DNA fragments after excision of Tn916 in Escherichia coli: strategy for targeting and cloning of genes from gram-positive bacteria. J Bacteriol 159:214–221

  24. Guild WR, Smith MD, Shoemaker NB (1982) Conjugative transfer of chromosomal R determinants in Streptococcus pneumoniae. In: Schlessinger D (ed) Microbiology-1982. American Society for Microbiology, Washington DC, pp 88–92

  25. Haas MJ, Dowding JE (1975) Aminoglycoside-modifying enzymes. Methods Enzymol 43:611–628

  26. Jacob AE, Hobbs SJ (1974) Conjugal transfer of plasmid-borne multiple antibiotic resistance in Streptococcus faecalis var. zymogenes. J Bacteriol 117:360–372

  27. Jacobs MR, Koornhof HJ, Robins-Browne RM, Stevenson CM, Freiman I, Miller GB, Witcomb MA, Isaacson M, Ward JI, Austrian R (1978) Emergence of multiply resistant pneumonocci. N Engl J Med 299:735–740

  28. Lambert T, Gerbaud G, Trieu-Cuot P, Courvalin P (1985) Structural relationship between the genes encoding 3′-aminoglycoside phosphotransferases type III from Campylobacter and Gram-positive cocci. Ann Microbiol Inst Pasteur (Paris) 136B:135–150

  29. Lederberg EM (1981) Plasmid reference center registry of transposon (Tn) allocations through July 1981. Gene 16:59–61

  30. Lereclus D, Menou G, Lecadet MM (1983) Isolation of a DNA sequence related to several plasmids from Bacillus thuringiensis after mating involving the Streptococcus faecalis plasmid pAMβ1. Mol Gen Genet 191:307–313

  31. Maniatis T, Fritsch EF, Sambrook J (1982) Molecular cloning: A laboratory manual. Cold Spring Harbor Laboratory. Cold Spring Harbor, NY

  32. Maniatis T, Jeffrey A, Kleid DG (1975) Nucleotide sequence of the rightward operator of phage λ. Proc Natl Acad Sci USA 72:1184–1188

  33. Martin P, Trieu-Cuot P, Courvalin P (1986) Nucleotide sequence of the tetM tetracycline resistance determinant of the streptococcol conjugative shuttle transposon Tn1545. Nucl Acids Res 17:7047–7058

  34. Novick RP, Clowes RC, Cohen SN, Curtiss III R, Datta N, Falkow S (1976) Uniform nomenclature for bacterial plasmids: a proposal. Bacteriol Rev 40:168–189

  35. Novick RP, Edelman I, Schwesinger MD, Gruss AD, Swanson EC, Pattee PA (1979) Genetic translocation in Staphylococcus aureus. Proc Natl Acad Sci USA 76:400–404

  36. Ounissi H, Courvalin P (1982) Heterogeneity of macrolide-lincosamide-streptogramin B-type antibiotic resistance determinants. In: Schlessinger D (ed) Microbiology-1982. American Society for Microbiology, Washington DC, pp 167–169

  37. Pakula R, Hulanicka E, Walczak W (1958) Transformation reactions between streptococci, pneumonocci, and staphylococci. Bull Acad Pol Sci 6:325–328

  38. Pérez-Diaz JC, Vicente MF, Baquero F (1982) Plasmids in Listeria. Plasmid 8:112–118

  39. Portnoy DA, Moseley SL, Flakow S (1981) Characterization of plasmids and plasmid-associated determinants of Yersinia enterocolitica pathogenesis. Infect Immun 31:775–782

  40. Sanger F, Coulson AR, Hong GF, Hill DF, Petersen GB (1982) Nucleotide sequence of bacteriophage lambda DNA. J Mol Biol 162:729–773

  41. Shoemaker NB, Smith MD, Guild WR (1979) Organization and transfer of heterologous chloramphenicol and tetracycline resistance genes in Pneumococcus. J Bacteriol 139:432–441

  42. Shoemaker NB, Smith MD, Guild WR (1980) DNase-resistant transfer of chromosomal cat and tet insertions by filter mating in Pneumococcus. Plasmid 3:80–87

  43. Shinnick TM, Lund E, Smithies O, Blattner FR (1975) Hybridization of labeled RNA to DNA in agarose gels. Nucleic Acids Res 2:1911–1929

  44. Smith MD, Shoemaker NB, Burdett V, Guild WR (1980) Transfer of plasmids by conjugation in Streptococcus pneumoniae. Plasmid 3:70–79

  45. Southern E (1975) Detection of specific sequence among DNA fagments separated by gel electrophoresis. J Mol Biol 98:503–517

  46. Terzaghi BE, Sandine WE (1975) Improved medium for lactic streptococci and their bacteriophages. Appl Microbiol 29:807–813

  47. Trieu-Cuot P, Gerbaud G, Lambert T, Courvalin P (1985) In vivo transfer of genetic information between Gram-positive and Gram-negative bacteria. EMBO J 4:3583–3587

  48. Véron M, Chatelain R (1973) Taxonomic study of the genus Campylobacter Sebald and Véron and designation of the neotype strain for the type species Campylobacter fetus (Smith and Taylor) Sebald and Véron. Int J Syst Bact 23:122–134

  49. Yagi Y, Clewell DB (1980) Recombination-deficient mutant of Streptococcus faecalis. J Bacteriol 143:966–970

Download references

Author information

Correspondence to Patrice Courvalin.

Additional information

Communicated by P. Tiollais

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Courvalin, P., Carlier, C. Transposable multiple antibiotic resistance in Streptococcus pneumoniae . Molec. Gen. Genet. 205, 291–297 (1986). https://doi.org/10.1007/BF00430441

Download citation

Key words

  • Pneumococcus
  • Antibiotic resistance
  • Conjugative transposon