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We investigated the fitness costs associated with the expression of six methyltransferases isolated from clinical strains (ArmA, RmtA, RmtB, RmtC, RmtD, and NpmA), and two methyltransferases from natural antibiotic producers (Sgm and KamB) in\n                      <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n                      . Growth competition assays revealed that methyltransferases found in natural producers imposed significantly lower fitness costs than those isolated from clinical strains, allowing resistant populations to persist at stable levels. Translational fidelity assays demonstrated that most methyltransferases induce error-prone phenotypes by allowing increased readthrough of nonsense codons and frameshift mutations, while KamB uniquely increased translational accuracy. Deletion of the housekeeping methyltransferase RsmF further altered these effects, highlighting the complex interplay between endogenous and exogenous methylation processes. Stress response experiments showed varying results: most methyltransferases increased susceptibility to hyperosmotic stress, while several (RmtB, RmtA, ArmA, and KamB) increased tolerance to acidic stress. These findings reveal that 16S rRNA methyltransferases play complex roles in bacterial physiology beyond antibiotic resistance, with important implications for the persistence of resistance and potential therapeutic strategies targeting specific vulnerabilities in resistant bacteria.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.00742-25","type":"journal-article","created":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T11:56:59Z","timestamp":1753963019000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["Biological cost of aminoglycoside resistance Arm\/Kam 16S rRNA methyltransferases from natural antibiotic producers and clinical pathogens"],"prefix":"10.1128","volume":"69","author":[{"given":"Darija","family":"Vidu\u010di\u0107","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00mv6sv71","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Molecular Biology, Faculty of Pharmacy and Biochemistry, University of Zagreb","place":["Zagreb, Croatia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9240-5982","authenticated-orcid":true,"given":"Sonja","family":"Obrani\u0107","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00mv6sv71","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Molecular Biology, Faculty of Pharmacy and Biochemistry, University of Zagreb","place":["Zagreb, Croatia"]},{"name":"University Centre Vara\u017edin, University North","place":["Vara\u017edin, Croatia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7647-3339","authenticated-orcid":true,"given":"Mihaela","family":"Matovina","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00mv6sv71","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Molecular Biology, Faculty of Pharmacy and Biochemistry, University of Zagreb","place":["Zagreb, Croatia"]},{"id":[{"id":"https:\/\/ror.org\/02mw21745","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Organic Chemistry and Biochemistry, Ru\u0111er Bo\u0161kovi\u0107 Institute","place":["Zagreb, Croatia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2290-6917","authenticated-orcid":true,"given":"Fedora","family":"Babi\u0107","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00mv6sv71","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Molecular Biology, Faculty of Pharmacy and Biochemistry, University of Zagreb","place":["Zagreb, Croatia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0253-4028","authenticated-orcid":true,"given":"Gordana","family":"Maravi\u0107-Vlahovi\u010dek","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00mv6sv71","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Molecular Biology, Faculty of Pharmacy and Biochemistry, University of Zagreb","place":["Zagreb, Croatia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-04265-w"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1503141112"},{"key":"e_1_3_2_4_2","unstructured":"World Health Organization (WHO). 2019. 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