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Consistent with this, a \u0394<jats:italic>amgR<\/jats:italic> strain showed increased aminoglycoside\u2010promoted membrane damage, damage that was largely absent in Amg<jats:styled-content style=\"fixed-case\">RS<\/jats:styled-content>\u2010activated <jats:italic>amgS\u2010<\/jats:italic>mutant strains. Intriguingly, one such mutation, V121G, while providing for enhanced resistance to aminoglycosides, rendered <jats:italic>P. aeruginosa<\/jats:italic> susceptible to several ribosome\u2010targeting nonaminoglycoside antimicrobials that are inducers and presumed substrates of the Mex<jats:styled-content style=\"fixed-case\">XY<\/jats:styled-content>\u2010OprM multidrug efflux system. Surprisingly, the <jats:italic>amg<\/jats:italic><jats:styled-content style=\"fixed-case\"><jats:italic>S<\/jats:italic><jats:sub>V<\/jats:sub><\/jats:styled-content><jats:sub>121G<\/jats:sub> mutation increased <jats:italic>mex<jats:styled-content style=\"fixed-case\">XY<\/jats:styled-content><\/jats:italic> expression threefold, suggesting that export of these nonaminoglycosides was compromised in the <jats:italic>amg<\/jats:italic><jats:styled-content style=\"fixed-case\"><jats:italic>S<\/jats:italic><jats:sub>V<\/jats:sub><\/jats:styled-content><jats:sub>121G<\/jats:sub> mutant. Nonetheless, a link was established between Amg<jats:styled-content style=\"fixed-case\">RS<\/jats:styled-content> activation and <jats:italic>mex<jats:styled-content style=\"fixed-case\">XY<\/jats:styled-content><\/jats:italic> expression and this was confirmed in studies showing that aminoglycoside\u2010promoted <jats:italic>mex<jats:styled-content style=\"fixed-case\">XY<\/jats:styled-content><\/jats:italic> expression is dependent on Amg<jats:styled-content style=\"fixed-case\">RS<\/jats:styled-content>. While nonaminoglycosides also induced <jats:italic>mex<jats:styled-content style=\"fixed-case\">XY<\/jats:styled-content><\/jats:italic> expression, this was not Amg<jats:styled-content style=\"fixed-case\">RS<\/jats:styled-content>\u2010dependent, consistent with these agents not generating mistranslated polypeptides and not activating Amg<jats:styled-content style=\"fixed-case\">RS<\/jats:styled-content>. The aminoglycoside inducibility of <jats:italic>mex<jats:styled-content style=\"fixed-case\">XY<\/jats:styled-content><\/jats:italic> was abrogated in a mutant lacking the Amg<jats:styled-content style=\"fixed-case\">RS<\/jats:styled-content> target genes <jats:italic>htpX<\/jats:italic> and PA5528, encoding a presumed cytoplasmic membrane\u2010associated protease and a membrane protein of unknown function, respectively. Thus, aminoglycoside induction of <jats:italic>mex<jats:styled-content style=\"fixed-case\">XY<\/jats:styled-content><\/jats:italic> is a response to membrane damage and activation of the Amg<jats:styled-content style=\"fixed-case\">RS<\/jats:styled-content> two\u2010component system.<\/jats:p>","DOI":"10.1002\/mbo3.226","type":"journal-article","created":{"date-parts":[[2014,12,1]],"date-time":"2014-12-01T08:12:44Z","timestamp":1417421564000},"page":"121-135","source":"Crossref","is-referenced-by-count":56,"title":["AmgRS\u2010mediated envelope stress\u2010inducible expression of the <i>mexXY<\/i> multidrug efflux operon of <i>Pseudomonas aeruginosa<\/i>"],"prefix":"10.1002","volume":"4","author":[{"given":"Calvin Ho\u2010Fung","family":"Lau","sequence":"first","affiliation":[{"name":"Department of Biomedical and Molecular Sciences Botterell Hall Queen's University Kingston Ontario K7L 3N6 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Krahn","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Molecular Sciences Botterell Hall Queen's University Kingston Ontario K7L 3N6 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christie","family":"Gilmour","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Molecular Sciences Botterell Hall Queen's University Kingston Ontario K7L 3N6 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin","family":"Mullen","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Molecular Sciences Botterell Hall Queen's University Kingston Ontario K7L 3N6 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Poole","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Molecular Sciences Botterell Hall Queen's University Kingston Ontario K7L 3N6 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,12]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.6.2246-2259.2005"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.43.11.2624"},{"key":"e_1_2_7_4_1","volume-title":"Short protocols in molecular biology","author":"Ausubel F. 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