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Antimicrobial Agents and Chemotherapy, August 2003, p. 2565-2571, Vol. 47, No. 8
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.8.2565-2571.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Plasmid-Mediated High-Level Resistance to Aminoglycosides in Enterobacteriaceae Due to 16S rRNA Methylation

Marc Galimand,1* Patrice Courvalin,1 and Thierry Lambert1,2

Unité des Agents Antibactériens, Institut Pasteur, 75724 Paris Cedex 15,1 Centre d'Etudes Pharmaceutiques, ChÂtenay-Malabry, France2

Received 5 February 2003/ Returned for modification 20 April 2003/ Accepted 17 May 2003

A self-transferable plasmid of ca. 80 kb, pIP1204, conferred multiple-antibiotic resistance to Klebsiella pneumoniae BM4536, which was isolated from a urinary tract infection. Resistance to ß-lactams was due to the blaTEM1 and blaCTX-M genes, resistance to trimethroprim was due to the dhfrXII gene, resistance to sulfonamides was due to the sul1 gene, resistance to streptomycin-spectinomycin was due to the ant3"9 gene, and resistance to nearly all remaining aminoglycosides was due to the aac3-II gene and a new gene designated armA (aminoglycoside resistance methylase). The cloning of armA into a plasmid in Escherichia coli conferred to the new host high-level resistance to 4,6-disubstituted deoxystreptamines and fortimicin. The deduced sequence of ArmA displayed from 37 to 47% similarity to those of 16S rRNA m7G methyltransferases from various actinomycetes, which confer resistance to aminoglycoside-producing strains. However, the low guanine-plus-cytosine content of armA (30%) does not favor an actinomycete origin for the gene. It therefore appears that posttranscriptional modification of 16S rRNA can confer high-level broad-range resistance to aminoglycosides in gram-negative human pathogens.

* Corresponding author. Mailing address: Unité des Agents Antibactériens, Institut Pasteur, 25, rue du Docteur Roux, 75724 Paris Cedex 15, France. Phone: (33) (1) 45 68 83 18. Fax: (33) (1) 45 68 83 19. E-mail: galimand{at}pasteur.fr.

Antimicrobial Agents and Chemotherapy, August 2003, p. 2565-2571, Vol. 47, No. 8
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.8.2565-2571.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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