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Volume 145, Issue 9

Dispensable ribosomal resistance to spiramycin conferred by in the spiramycin producer

The EMBL/GenBank accession number for the nucleotide sequence described in this paper is AJ223970.

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Abstract

produces the macrolide antibiotic spiramycin, an inhibitor of protein synthesis, and possesses multiple resistance mechanisms to the produced antibiotic. Several resistance determinants have been isolated from and studies with one of them, , which hybridized with (the erythromycin-resistance gene from ), are detailed here. The nucleotide sequence of was determined and the mechanism by which its product confers resistance was characterized. The SrmA protein is a methyltransferase which introduces a single methyl group into A-2058 ( numbering scheme) in the large rRNA, thereby conferring an MLS (macrolide–lincosamide–streptogramin type B) type I resistance phenotype. A mutant of in which was inactivated was viable and still produced spiramycin, indicating that is dispensable, at least in the presence of the other resistance determinants.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): macrolide antibiotics , MLS resistance , MLS, macrolide–lincosamide–streptogramin type B , rRNA methylation , SAM, S-adenosylmethionine , spiramycin and Streptomyces ambofaciens
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1999-09-01
2024-05-10
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References

  1. Altschul S. F., Madden T. L., Schaffer A. A., Zhang J., Zhang Z., Miller W., Lipman D. J. 1997; Gapped blast and psi-blast: a new generation of protein database search programs. Nucleic Acids Res 25:3389–3402 [CrossRef]
     [Google Scholar]
  2. Arthur M., Autissier D., Courvalin P. 1986; Analysis of the nucleotide sequence of the ereB gene encoding the erythromycin esterase type II. Nucleic Acids Res 14:4987–4999 [CrossRef]
     [Google Scholar]
  3. Baltz R. H., Seno E. T. 1988; Genetics of Streptomyces fradiae and tylosin biosynthesis. Annu Rev Microbiol 42:547–574 [CrossRef]
     [Google Scholar]
  4. Bibb M. J., Findlay P. R., Johnson M. W. 1984; The relationship between base composition and codon usage in bacterial genes and its use for the simple and reliable identification of protein-coding sequences. Gene 30:157–166 [CrossRef]
     [Google Scholar]
  5. Bierman M., Logan R., O’Brien K., Seno E. T., Rao R. N., Schoner B. E. 1992; Plasmid cloning vectors for the conjugal transfer of DNA from Escherichia coli to Streptomyces spp. Gene 116:43–49 [CrossRef]
     [Google Scholar]
  6. Birmingham V. A., Cox K. L., Larson J. L., Fishman S. E., Hershberger C. L., Seno E. T. 1986; Cloning and expression of a tylosin resistance gene from a tylosin-producing strain of Streptomyces fradiae. Mol Gen Genet 204:532–539 [CrossRef]
     [Google Scholar]
  7. Blondelet-Rouault M.-H., Weiser J., Lebrihi A, Branny P., Pernodet J.-L. 1997; Antibiotic resistance gene cassettes derived from the omega interposon for use in E. coli and Streptomyces. Gene 190:315–317 [CrossRef]
     [Google Scholar]
  8. Boyer H. W., Roulland-Dussoix D. 1969; A complementation analysis of the restriction and modification of DNA in Escherichia coli. J Mol Biol 41:459–472 [CrossRef]
     [Google Scholar]
  9. Brisson-Noël A., Trieu-Cuot P., Courvalin P. 1988; Mechanism of action of spiramycin and other macrolides. J Antimicrob Chemother 22:Suppl B13–23
     [Google Scholar]
  10. Calcutt M. J., Cundliffe E. 1989; Use of a fractionated coupled transcription–translation system in the study of ribosomal resistance mechanisms in antibiotic-producing Streptomyces. J Gen Microbiol 135:1071–1081
     [Google Scholar]
  11. Calcutt M. J., Cundliffe E. 1990; Cloning of a lincosamide resistance determinant from Streptomyces caelestis, the producer of celesticetin, and characterization of the resistance mechanism. J Bacteriol 172:4710–4714
     [Google Scholar]
  12. Cox K. L., Baltz R. H. 1984; Restriction of bacteriophage plaque formation in Streptomyces spp. J Bacteriol 159:499–504
     [Google Scholar]
  13. Cundliffe E. 1989; How antibiotic-producing organisms avoid suicide. Annu Rev Microbiol 43:207–233 [CrossRef]
     [Google Scholar]
  14. Cundliffe E. 1992; Glycosylation of macrolide antibiotics in extracts of Streptomyces lividans. Antimicrob Agents Chemother 36:348–352 [CrossRef]
     [Google Scholar]
  15. Dhillon N., Leadlay P. F. 1990; A repeated decapeptide motif in the C-terminal domain of the ribosomal RNA methyltransferase from the erythromycin producer Saccharopolyspora erythraea. FEBS Lett 262:189–193 [CrossRef]
     [Google Scholar]
  16. Epp J. K., Burgett S. G., Schoner B. E. 1987; Cloning and nucleotide sequence of a carbomycin-resistance gene from Streptomyces thermotolerans. Gene 53:73–83 [CrossRef]
     [Google Scholar]
  17. Fahnestock S., Erdmann V., Nomura M. 1974; Reconstitution of 50 S ribosomal subunits from Bacillus stearothermophilus. Methods Enzymol 30:554–562
     [Google Scholar]
  18. Fierro J. F., Hardisson C., Salas J.-A. 1987; Resistance to oleandomycin in Streptomyces antibioticus, the producer organism. J Gen Microbiol 133:1931–1939
     [Google Scholar]
  19. Gale E. F., Cundliffe E., Reynolds P. E., Richmond M. H., Waring M. J. 1981 The Molecular Basis of Antibiotic Action London: Wiley;
     [Google Scholar]
  20. Gourmelen A., Blondelet-Rouault M.-H., Pernodet J.-L. 1998; Characterization of a glycosyl transferase inactivating macrolides, encoded by gimA from Streptomyces ambofaciens. Antimicrob Agents Chemother 42:2612–2619
     [Google Scholar]
  21. Hara O., Hutchinson C. R. 1990; Cloning of midecamycin(MLS)-resistance genes from Streptomyces mycarofaciens, Streptomyces lividans and Streptomyces coelicolor A3(2). J Antibiot 43:977–991 [CrossRef]
     [Google Scholar]
  22. Hernandez C., Olano C., Mendez C., Salas J.-A. 1993; Characterization of a Streptomyces antibioticus gene cluster encoding a glycosyltransferase involved in oleandomycin inactivation. Gene 134:139–140 [CrossRef]
     [Google Scholar]
  23. Hopwood D. A., Kieser T., Wright H. M., Bibb M. J. 1983; Plasmids, recombination and chromosome mapping in Streptomyces lividans 66. J Gen Microbiol 129:2257–2269
     [Google Scholar]
  24. Hopwood D. A., Bibb M. J., Chater K. F.7 other authors 1985 Genetic Manipulation of Streptomyces: a Laboratory Manual Norwich: John Innes Foundation;
     [Google Scholar]
  25. Inouye M., Morohoshi T., Horinouchi S., Beppu T. 1994; Cloning and sequences of two macrolide-resistance-encoding genes from mycinamicin-producing Micromonospora griseorubida. Gene 141:39–46 [CrossRef]
     [Google Scholar]
  26. Jenkins G., Cundliffe E. 1991; Cloning and characterization of two genes from Streptomyces lividans that confer inducible resistance to lincomycin and macrolide antibiotics. Gene 108:55–62 [CrossRef]
     [Google Scholar]
  27. Jenkins G., Zalacain M., Cundliffe E. 1989; Inducible ribosomal RNA methylation in Streptomyces lividans, conferring resistance to lincomycin. J Gen Microbiol 135:3281–3288
     [Google Scholar]
  28. Kagan R. M., Clarke S. 1994; Widespread occurrence of three sequence motifs in diverse S-adenosylmethionine-dependent methyltransferases suggests a common structure for these enzymes. Arch Biochem Biophys 310:417–427 [CrossRef]
     [Google Scholar]
  29. Kamimiya S., Weisblum B. 1988; Translational attenuation control of ermSF, an inducible resistance determinant encoding rRNA N-methyltransferase from Streptomyces fradiae. J Bacteriol 170:1800–1811
     [Google Scholar]
  30. Kamimiya S., Weisblum B. 1997; Induction of ermSV by 16-membered-ring macrolide antibiotics. Antimicrob Agents Chemother 41:530–534
     [Google Scholar]
  31. Kelemen G. H., Zalacain M., Culebras E., Seno E. T., Cundliffe E. 1994; Transcriptional attenuation control of the tylosin-resistance gene tlrA in Streptomyces fradiae. Mol Microbiol 14:833–842 [CrossRef]
     [Google Scholar]
  32. Kuo M. S., Chirby D. G., Argoudelis A. D., Cialdella J. I., Coats J. H., Marshall V. P. 1989; Microbial glycosylation of erythromycin A. Antimicrob Agents Chemother 33:2089–2091 [CrossRef]
     [Google Scholar]
  33. Lydiate D. J., Malpartida F., Hopwood D. A. 1985; The Streptomyces plasmid SCP2*: its functional analysis and development into useful cloning vectors. Gene 35:223–235 [CrossRef]
     [Google Scholar]
  34. Marshall V. P., Cialdella J. I., Baczynskyj L., Liggett W. F., Johnson R. A. 1989; Microbial O-phosphorylation of macrolide antibiotics. J Antibiot 42:132–134 [CrossRef]
     [Google Scholar]
  35. Mead D. A., Szczesna-Skorupa E., Kemper B. 1986; Single-stranded DNA ‘blue’ T7 promoter plasmids: a versatile tandem promoter system for cloning and protein engineering. Protein Eng 1:67–74 [CrossRef]
     [Google Scholar]
  36. Mendez C., Salas J.-A. 1998; ABC transporters in antibiotic-producing actinomycetes. FEMS Microbiol Lett 158:1–8 [CrossRef]
     [Google Scholar]
  37. O’Hara K., Kanda T., Ohmiya K, Ebisu T., Kono M. 1989; Purification and characterization of macrolide 2′-phosphotransferase from a strain of Escherichia coli that is highly resistant to erythromycin. Antimicrob Agents Chemother 33:1354–1357 [CrossRef]
     [Google Scholar]
  38. Olano C., Rodriguez A. M., Mendez C., Salas J.-A. 1995; A second ABC transporter is involved in oleandomycin resistance and its secretion by Streptomyces antibioticus. Mol Microbiol 16:333–343 [CrossRef]
     [Google Scholar]
  39. Ounissi H., Courvalin P. 1985; Nucleotide sequence of the gene ereA encoding the erythromycin esterase in Escherichia coli. Gene 35:271–278 [CrossRef]
     [Google Scholar]
  40. Pearson W. R., Lipman D. J. 1988; Improved tools for biological sequence comparison. Proc Natl Acad Sci USA 85:2444–2448 [CrossRef]
     [Google Scholar]
  41. Pernodet J.-L., Alegre, M.-T., Blondelet-Rouault, M.-H., Guérineau M. 1993; Resistance to spiramycin in Streptomyces ambofaciens, the producer organism, involves at least two different mechanisms. J Gen Microbiol 139:1003–1011 [CrossRef]
     [Google Scholar]
  42. Pernodet J.-L., Fish, S., Blondelet-Rouault, M.-H., Cundliffe E. 1996; The macrolide-lincosamide-streptogramin B resistance phenotypes characterized by using a specifically deleted, antibiotic-sensitive strain of Streptomyces lividans. Antimicrob Agents Chemother 40:581–585
     [Google Scholar]
  43. Pinnert-Sindico S. 1954; Une nouvelle espèce de Streptomyces productrice d’antibiotiques: Streptomyces ambofaciens n. sp. caractères culturaux. Ann Inst Pasteur (Paris) 87:702–707
     [Google Scholar]
  44. Pridham T. G., Anderson P., Foley C., Lindenfelser L. A., Hesseltine C. W., Benetdict R. C. 1957; A selection of media for maintenance and taxonomic study of Streptomyces. Antibiot Annu 1956–57947–953
     [Google Scholar]
  45. Quiros L. M., Aguirrezabalaga I., Olano C., Mendez C., Salas J.-A. 1998; Two glycosyltransferases and a glycosidase are involved in oleandomycin modification during its biosynthesis by Streptomyces antibioticus. Mol Microbiol 28:1177–1185 [CrossRef]
     [Google Scholar]
  46. Rao R. N., Richardson M. A., Kuhstoss S. 1987; Cosmid shuttle vectors for cloning and analysis of Streptomyces DNA. Methods Enzymol 153:166–198
     [Google Scholar]
  47. Richardson M. A., Kuhstoss S., Solenberg P., Schaus N. A., Rao R. N. 1987; A new shuttle cosmid vector, pKC505, for streptomycetes: its use in the cloning of three different spiramycin-resistance genes from a Streptomyces ambofaciens library. Gene 61:231–241 [CrossRef]
     [Google Scholar]
  48. Rodriguez A.-M., Olano, C., Vilches, C, Mendez C., Salas J.-A. 1993; Streptomyces antibioticus contains at least three oleandomycin-resistance determinants, one of which shows similarity with proteins of the ABC-transporter superfamily. Mol Microbiol 8:571–582 [CrossRef]
     [Google Scholar]
  49. Ross J. I., Eady E. A., Cove J. H., Cunliffe W. J., Baumberg S., Wootton J. C. 1990; Inducible erythromycin resistance in staphylococci is encoded by a member of the ATP-binding transport super-gene family. Mol Microbiol 4:1207–1214 [CrossRef]
     [Google Scholar]
  50. Rosteck P. R. Jr, Reynolds P. A., Hershberger C. L. 1991; Homology between proteins controlling Streptomyces fradiae tylosin resistance and ATP-binding transport. Gene 102:27–32 [CrossRef]
     [Google Scholar]
  51. Sambrook J., Fritsch E. F., Maniatis T. 1989 Molecular Cloning: a Laboratory Manual Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
     [Google Scholar]
  52. Schluckebier G., O’Gara M, Saenger W., Cheng X. 1995; Universal catalytic domain structure of AdoMet-dependent methyltransferases. J Mol Biol 247:16–20 [CrossRef]
     [Google Scholar]
  53. Schoner B., Geistlich M., Rosteck P. Jr, Rao R. N., Seno E., Reynolds P., Cox, K, Burgett S., Hershberger C. 1992; Sequence similarity between macrolide-resistance determinants and ATP-binding transport proteins. Gene 115:93–96 [CrossRef]
     [Google Scholar]
  54. Simon R., Priefer U., Pühler A. 1983; A broad host range mobilisation system for in vivo genetic engineering: transposon mutagenesis in gram-negative bacteria. Bio/Technology 1:784–791 [CrossRef]
     [Google Scholar]
  55. Skeggs P. A., Thompson J., Cundliffe E. 1985; Methylation of 16S ribosomal RNA and resistance to aminoglycoside antibiotics in clones of Streptomyces lividans carrying DNA from Streptomyces tenjimariensis. Mol Gen Genet 200:415–421 [CrossRef]
     [Google Scholar]
  56. Thompson J., Rae S., Cundliffe E. 1984; Coupled transcription-translation in extracts of Streptomyces lividans. Mol Gen Genet 195:39–43 [CrossRef]
     [Google Scholar]
  57. Uchiyama H., Weisblum B. 1985; N-Methyl transferase of Streptomyces erythraeus that confers resistance to the macrolide-lincosamide-streptogramin B antibiotics: amino acid sequence and its homology to cognate R-factor enzymes from pathogenic bacilli and cocci. Gene 38:103–110 [CrossRef]
     [Google Scholar]
  58. Vilches C., Hernandez C., Mendez C., Salas J.-A. 1992; Role of glycosylation and deglycosylation in biosynthesis of and resistance to oleandomycin in the producer organism, Streptomyces antibioticus. J Bacteriol 174:161–165
     [Google Scholar]
  59. Ward J. M., Janssen G. R., Kieser T., Bibb M. J., Buttner M. J., Bibb M. J. 1986; Construction and characterisation of a series of multi-copy promoter-probe plasmid vectors for Streptomyces using the aminoglycoside phosphotransferase gene from Tn5 as indicator. Mol Gen Genet 203:468–478 [CrossRef]
     [Google Scholar]
  60. Weisblum B. 1995; Erythromycin resistance by ribosome modification. Antimicrob Agents Chemother 39:577–585 [CrossRef]
     [Google Scholar]
  61. Yanisch-Perron C, Vieira J., Messing J. 1985; Improved M13 phage cloning vectors and host strains: nucleotide sequences of the M13mp18 and pUC19 vectors. Gene 33:103–119 [CrossRef]
     [Google Scholar]
  62. Zalacain M., Cundliffe E. 1989; Methylation of 23S rRNA caused by tlrA (ermSF), a tylosin resistance determinant from Streptomyces fradiae. J Bacteriol 171:4254–4260
     [Google Scholar]
  63. Zalacain M., Cundliffe E. 1991; Cloning of tlrD, a fourth resistance gene, from the tylosin producer, Streptomyces fradiae. Gene 97:137–142 [CrossRef]
     [Google Scholar]
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Dispensable ribosomal resistance to spiramycin conferred by srmA in the spiramycin producer Streptomyces ambofaciensThe EMBL/GenBank accession number for the nucleotide sequence described in this paper is AJ223970.
Microbiology 145, 2355 (1999); https://doi.org/10.1099/00221287-145-9-2355
/content/journal/micro/10.1099/00221287-145-9-2355
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