{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:57:00Z","timestamp":1790776620458,"version":"4.1.0"},"reference-count":36,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2012,5,1]],"date-time":"2012-05-01T00:00:00Z","timestamp":1335830400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2012,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Arm\/Rmt methyltransferases have emerged recently in pathogenic bacteria as enzymes that confer high-level resistance to 4,6-disubstituted aminoglycosides through methylation of the G1405 residue in the 16S rRNA (like ArmA and RmtA to -E). In prokaryotes, nucleotide methylations are the most common type of rRNA modification, and they are introduced posttranscriptionally by a variety of site-specific housekeeping enzymes to optimize ribosomal function. Here we show that while the aminoglycoside resistance methyltransferase RmtC methylates G1405, it impedes methylation of the housekeeping methyltransferase RsmF at position C1407, a nucleotide that, like G1405, forms part of the aminoglycoside binding pocket of the 16S rRNA. To understand the origin and consequences of this phenomenon, we constructed a series of in-frame knockout and knock-in mutants of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Escherichia coli<\/jats:named-content>\n            , corresponding to the genotypes\n            <jats:italic>rsmF<\/jats:italic>\n            <jats:sup>+<\/jats:sup>\n            , \u0394\n            <jats:italic>rsmF<\/jats:italic>\n            ,\n            <jats:italic>rsmF<\/jats:italic>\n            <jats:sup>+<\/jats:sup>\n            <jats:italic>rmtC<\/jats:italic>\n            <jats:sup>+<\/jats:sup>\n            , and \u0394\n            <jats:italic>rsmF rmtC<\/jats:italic>\n            <jats:sup>+<\/jats:sup>\n            . When analyzed for the antimicrobial resistance pattern, the \u0394\n            <jats:italic>rsmF<\/jats:italic>\n            bacteria had a decreased susceptibility to aminoglycosides, including 4,6- and 4,5-deoxystreptamine aminoglycosides, showing that the housekeeping methylation at C1407 is involved in intrinsic aminoglycoside susceptibility in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">E. coli<\/jats:named-content>\n            . Competition experiments between the isogenic\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">E. coli<\/jats:named-content>\n            strains showed that, contrary to expectation, acquisition of\n            <jats:italic>rmtC<\/jats:italic>\n            does not entail a fitness cost for the bacterium. Finally, matrix-assisted laser desorption ionization (MALDI) mass spectrometry allowed us to determine that RmtC methylates the G1405 residue not only in presence but also in the absence of aminoglycoside antibiotics. Thus, the coupling between housekeeping and acquired methyltransferases subverts the methylation architecture of the 16S rRNA but elicits Arm\/Rmt methyltransferases to be selected and retained, posing an important threat to the usefulness of aminoglycosides worldwide.\n          <\/jats:p>","DOI":"10.1128\/aac.06066-11","type":"journal-article","created":{"date-parts":[[2012,2,14]],"date-time":"2012-02-14T04:11:22Z","timestamp":1329192682000},"page":"2335-2341","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":42,"title":["Fitness Cost and Interference of Arm\/Rmt Aminoglycoside Resistance with the RsmF Housekeeping Methyltransferases"],"prefix":"10.1128","volume":"56","author":[{"given":"Belen","family":"Gutierrez","sequence":"first","affiliation":[{"name":"Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad Complutense de Madrid, Madrid, Spain"},{"name":"Centro de Vigilancia Sanitaria Veterinaria, Universidad Complutense de Madrid, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose A.","family":"Escudero","sequence":"additional","affiliation":[{"name":"Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad Complutense de Madrid, Madrid, Spain"},{"name":"Centro de Vigilancia Sanitaria Veterinaria, Universidad Complutense de Madrid, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvaro","family":"San Millan","sequence":"additional","affiliation":[{"name":"Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad Complutense de Madrid, Madrid, Spain"},{"name":"Centro de Vigilancia Sanitaria Veterinaria, Universidad Complutense de Madrid, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Hidalgo","sequence":"additional","affiliation":[{"name":"Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad Complutense de Madrid, Madrid, Spain"},{"name":"Centro de Vigilancia Sanitaria Veterinaria, Universidad Complutense de Madrid, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Carrilero","sequence":"additional","affiliation":[{"name":"Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad Complutense de Madrid, Madrid, Spain"},{"name":"Centro de Vigilancia Sanitaria Veterinaria, Universidad Complutense de Madrid, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina M.","family":"Ovejero","sequence":"additional","affiliation":[{"name":"Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad Complutense de Madrid, Madrid, Spain"},{"name":"Centro de Vigilancia Sanitaria Veterinaria, Universidad Complutense de Madrid, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"Santos-Lopez","sequence":"additional","affiliation":[{"name":"Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad Complutense de Madrid, Madrid, Spain"},{"name":"Centro de Vigilancia Sanitaria Veterinaria, Universidad Complutense de Madrid, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Thomas-Lopez","sequence":"additional","affiliation":[{"name":"Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad Complutense de Madrid, Madrid, Spain"},{"name":"Centro de Vigilancia Sanitaria Veterinaria, Universidad Complutense de Madrid, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Gonzalez-Zorn","sequence":"additional","affiliation":[{"name":"Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad Complutense de Madrid, Madrid, Spain"},{"name":"Centro de Vigilancia Sanitaria Veterinaria, Universidad Complutense de Madrid, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1016\/j.jmb.2006.04.007","article-title":"YebU is a m5C methyltransferase specific for 16S rRNA nucleotide 1407","volume":"359","author":"Andersen NM","year":"2006","unstructured":"AndersenNM DouthwaiteS. 2006. 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