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Microbiology 145 (1999), 2355-2364
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Microbiology (1999), 145, 2355-2364.
© 1999 Society for General Microbiology

Molecular Genetics of Streptomycetes

Dispensable ribosomal resistance to spiramycin conferred by srmA in the spiramycin producer Streptomyces ambofaciens

Jean-Luc Pernodet1, Anne Gourmelen1, Marie-Hélène Blondelet-Rouault1 and Eric Cundliffe2

Institut de Génétique et Microbiologie, UMR CNRS 8621, Bât. 400, Université Paris-Sud XI, F-91405 Orsay Cedex, France1
Department of Biochemistry, University of Leicester, Leicester LE1 7RH, UK2

Author for correspondence: Jean-Luc Pernodet. Tel: +33 1 69 15 46 41. Fax: +33 1 69 15 72 96. e-mail: pernodet{at}igmors.u-psud.fr

Streptomyces ambofaciens 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 S. ambofaciens and studies with one of them, srmA, which hybridized with ermE (the erythromycin-resistance gene from Saccharopolyspora erythraea), are detailed here. The nucleotide sequence of srmA 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 (Escherichia coli numbering scheme) in the large rRNA, thereby conferring an MLS (macrolide–lincosamide–streptogramin type B) type I resistance phenotype. A mutant of S. ambofaciens in which srmA was inactivated was viable and still produced spiramycin, indicating that srmA is dispensable, at least in the presence of the other resistance determinants.

Keywords: macrolide antibiotics, MLS resistance, rRNA methylation, spiramycin, Streptomyces ambofaciens

Abbreviations: MLS, macrolide–lincosamide–streptogramin type B; SAM, S-adenosylmethionine

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




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