{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T05:28:28Z","timestamp":1793942908832,"version":"4.8.0"},"reference-count":72,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2013,5,1]],"date-time":"2013-05-01T00:00:00Z","timestamp":1367366400000},"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":[[2013,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The\n            <jats:italic>amgRS<\/jats:italic>\n            operon encodes a presumed membrane stress-responsive two-component system linked to intrinsic aminoglycoside resistance in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Pseudomonas aeruginosa<\/jats:named-content>\n            . Genome sequencing of a lab isolate showing modest pan-aminoglycoside resistance, strain K2979, revealed a number of mutations, including a substitution in\n            <jats:italic>amgS<\/jats:italic>\n            that produced an R182C change in the AmgS sensor kinase product of this gene. Introduction of this mutation into an otherwise wild-type strain recapitulated the resistance phenotype, while correcting the mutation in the resistant mutant abrogated the resistant phenotype, confirming that the\n            <jats:italic>amgS<\/jats:italic>\n            mutation is responsible for the aminoglycoside resistance of strain K2979. The\n            <jats:italic>amgS<\/jats:italic>\n            <jats:sub>R182<\/jats:sub>\n            mutation promoted an AmgR-dependent, 2- to 3-fold increase in expression of the AmgRS target genes\n            <jats:italic>htpX<\/jats:italic>\n            and PA5528, mirroring the impact of aminoglycoside exposure of wild-type cells on\n            <jats:italic>htpX<\/jats:italic>\n            and PA5528 expression. This suggests that\n            <jats:italic>amgS<\/jats:italic>\n            <jats:sub>R182<\/jats:sub>\n            is a gain-of-function mutation that activates AmgS and the AmgRS two-component system in promoting modest resistance to aminoglycosides. Screening of several pan-aminoglycoside-resistant clinical isolates of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">P. aeruginosa<\/jats:named-content>\n            revealed three that showed elevated\n            <jats:italic>htpX<\/jats:italic>\n            and PA5528 expression and harbored single amino acid-altering mutations in\n            <jats:italic>amgS<\/jats:italic>\n            (V121G or D106N) and no mutations in\n            <jats:italic>amgR<\/jats:italic>\n            . Introduction of the\n            <jats:italic>amgS<\/jats:italic>\n            <jats:sub>V121G<\/jats:sub>\n            mutation into wild-type\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">P. aeruginosa<\/jats:named-content>\n            generated a resistance phenotype reminiscent of the\n            <jats:italic>amgS<\/jats:italic>\n            <jats:sub>R182<\/jats:sub>\n            mutant and produced a 2- to 3-fold increase in\n            <jats:italic>htpX<\/jats:italic>\n            and PA5528 expression, confirming that it, too, is a gain-of-function aminoglycoside resistance-promoting mutation. These results highlight the contribution of\n            <jats:italic>amgS<\/jats:italic>\n            mutations and activation of the AmgRS two-component system to acquired aminoglycoside resistance in lab and clinical isolates of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">P. aeruginosa<\/jats:named-content>\n            .\n          <\/jats:p>","DOI":"10.1128\/aac.00170-13","type":"journal-article","created":{"date-parts":[[2013,3,5]],"date-time":"2013-03-05T11:26:17Z","timestamp":1362482777000},"page":"2243-2251","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":53,"title":["Mutational Activation of the AmgRS Two-Component System in Aminoglycoside-Resistant Pseudomonas aeruginosa"],"prefix":"10.1128","volume":"57","author":[{"given":"Calvin Ho-Fung","family":"Lau","sequence":"first","affiliation":[{"name":"Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastien","family":"Fraud","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Jones","sequence":"additional","affiliation":[{"name":"The J. Craig Venter Institute, Rockville, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott N.","family":"Peterson","sequence":"additional","affiliation":[{"name":"The J. Craig Venter Institute, Rockville, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Poole","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1086\/591861"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00469-10"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.15.2.194-222.2002"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2009.08.004"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2005.01217.x"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2011.00065"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.2.479-487.2005"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/mr.51.3.341-350.1987"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.83.16.6164"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1219192"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.06.049"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.09.038"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11373-007-9194-y"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-005-0279-0"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2012.05.001"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)14959-8"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2010.08.003"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2004.00991.x"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2008.02097.x"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.47.10.3202-3207.2003"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.43.12.2975"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2012.00408"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01024-08"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00704-06"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00315-10"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01446-12"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0903619106"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.35.7.1309"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.37.4.715"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/mr.51.4.439-457.1987"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.05133-11"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01495-10"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1186\/1472-6750-9-61"},{"key":"e_1_3_2_35_2","volume-title":"Molecular cloning: a laboratory manual","author":"Sambrook J","year":"2001","unstructured":"SambrookJ RussellDW. 2001. 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