Plasmid-Mediated 16S rRNA Methylase in Serratia marcescens Conferring High-Level Resistance to Aminoglycosides

Yohei Doi, Keiko Yokoyama, Kunikazu Yamane, Jun Ichi Wachino, Naohiro Shibata, Tetsuya Yagi, Keigo Shibayama, Haru Kato, Yoshichika Arakawa

Research output: Contribution to journalArticle

148 Citations (Scopus)

Abstract

Serratia marcescens S-95, which displayed an unusually high degree of resistance to aminoglycosides, including kanamycins and gentamicins, was isolated in 2002 from a patient in Japan. The resistance was mediated by a large plasmid which was nonconjugative but transferable to an Escherichia coli recipient by transformation. The gene responsible for the aminoglycoside resistance was cloned and sequenced. The deduced amino acid sequence of the resistance gene shared 82% identity with RmtA, which was recently identified as 16S rRNA methylase conferring high-level aminoglycoside resistance in Pseudomonas aeruginosa. Histidine-tagged recombinant protein showed methylation activity against E. coli 16S rRNA. The novel aminoglycoside resistance gene was therefore designated rmtB. The genetic environment of rmtB was further investigated. The sequence immediately upstream of rmtB contained the right end of transposon Tn3, including blaTEM, while an open reading frame possibly encoding a transposase was identified downstream of the gene. This is the first report describing 16S rRNA methylase production in S. marcescens. The aminoglycoside resistance mechanism mediated by production of 16S rRNA methylase and subsequent ribosomal protection used to be confined to aminoglycoside-producing actinomycetes. However, it is now identified among pathogenic bacteria, including Enterobacteriaceae and P. aeruginosa in Japan. This is a cause for concern since other treatment options are often limited in patients requiring highly potent aminoglycosides such as amikacin and tobramycin.

Original languageEnglish
Pages (from-to)491-496
Number of pages6
JournalAntimicrobial Agents and Chemotherapy
Volume48
Issue number2
DOIs
Publication statusPublished - 01-02-2004
Externally publishedYes

Fingerprint

Serratia marcescens
Aminoglycosides
Plasmids
Pseudomonas aeruginosa
Genes
Japan
Escherichia coli
Transposases
Tobramycin
Kanamycin
Amikacin
Actinobacteria
Enterobacteriaceae
rRNA (adenosine-O-2'-)methyltransferase
Gentamicins
Recombinant Proteins
Histidine
Methylation
Open Reading Frames
Amino Acid Sequence

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Doi, Yohei ; Yokoyama, Keiko ; Yamane, Kunikazu ; Wachino, Jun Ichi ; Shibata, Naohiro ; Yagi, Tetsuya ; Shibayama, Keigo ; Kato, Haru ; Arakawa, Yoshichika. / Plasmid-Mediated 16S rRNA Methylase in Serratia marcescens Conferring High-Level Resistance to Aminoglycosides. In: Antimicrobial Agents and Chemotherapy. 2004 ; Vol. 48, No. 2. pp. 491-496.
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Doi, Y, Yokoyama, K, Yamane, K, Wachino, JI, Shibata, N, Yagi, T, Shibayama, K, Kato, H & Arakawa, Y 2004, 'Plasmid-Mediated 16S rRNA Methylase in Serratia marcescens Conferring High-Level Resistance to Aminoglycosides', Antimicrobial Agents and Chemotherapy, vol. 48, no. 2, pp. 491-496. https://doi.org/10.1128/AAC.48.2.491-496.2004

Plasmid-Mediated 16S rRNA Methylase in Serratia marcescens Conferring High-Level Resistance to Aminoglycosides. / Doi, Yohei; Yokoyama, Keiko; Yamane, Kunikazu; Wachino, Jun Ichi; Shibata, Naohiro; Yagi, Tetsuya; Shibayama, Keigo; Kato, Haru; Arakawa, Yoshichika.

In: Antimicrobial Agents and Chemotherapy, Vol. 48, No. 2, 01.02.2004, p. 491-496.

Research output: Contribution to journalArticle

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T1 - Plasmid-Mediated 16S rRNA Methylase in Serratia marcescens Conferring High-Level Resistance to Aminoglycosides

AU - Doi, Yohei

AU - Yokoyama, Keiko

AU - Yamane, Kunikazu

AU - Wachino, Jun Ichi

AU - Shibata, Naohiro

AU - Yagi, Tetsuya

AU - Shibayama, Keigo

AU - Kato, Haru

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