Plasmid-mediated high-level resistance to aminoglycosides in Enterobacteriaceae due to 16S rRNA methylation.
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 beta-lactams was due to the bla(TEM1) and bla(CTX-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 m(7)G 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.
Galimand
Marc
M
Unité des Agents Antibactériens, Institut Pasteur, 75724 Paris Cedex 15, France. galimand@pasteur.fr
Courvalin
Patrice
P
Lambert
Thierry
T
D000595:Amino Acid Sequence; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics; D004269:DNA, Bacterial / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial; D004755:Enterobacteriaceae / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics*; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000235:genetics; D008745:Methylation; D008780:Methyltransferases / Q000235:genetics* / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010957:Plasmids / Q000235:genetics*; D012336:RNA, Ribosomal, 16S / Q000235:genetics*
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D012336:RNA, Ribosomal, 16S; C446079:16S rRNA - m7G methyltransferase; D008780:Methyltransferases