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Fraud and K. Poole, Antimicrob. Agents Chemother. 55:1068\u20131074, 2011). Genome sequencing of one of these mutants, K2966, revealed the presence of a mutation within the predicted promoter region of the\n            <jats:italic>rplU-rpmA<\/jats:italic>\n            operon encoding ribosomal proteins L21 and L27, consistent with an observed 2-fold decrease in expression of this operon in the mutant relative to 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            PAO1. Moreover, correction of the mutation restored\n            <jats:italic>rplU-rpmA<\/jats:italic>\n            expression and, significantly, reversed the elevated\n            <jats:italic>mexXY<\/jats:italic>\n            expression and pan-aminoglycoside resistance of the mutant. Reduced\n            <jats:italic>rplU-rpmA<\/jats:italic>\n            expression was also observed in a second\n            <jats:italic>mexXY<\/jats:italic>\n            -expressing pan-aminoglycoside-resistant mutant, K2968, which, however, lacked a mutation in the\n            <jats:italic>rplU-rpmA<\/jats:italic>\n            promoter region. Restoration of\n            <jats:italic>rplU-rpmA<\/jats:italic>\n            expression in the K2968 mutant following chromosomal integration of the\n            <jats:italic>rplU-rpmA<\/jats:italic>\n            operon derived from 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            failed, however, to reverse the elevated\n            <jats:italic>mexXY<\/jats:italic>\n            expression and pan-aminoglycoside resistance of this mutant, although it did so for K2966, suggesting that the mutation impacting\n            <jats:italic>rplU-rpmA<\/jats:italic>\n            expression in K2968 also impacts other\n            <jats:italic>mexXY<\/jats:italic>\n            -related genes. Increased\n            <jats:italic>mexXY<\/jats:italic>\n            expression owing to reduced\n            <jats:italic>rplU-rpmA<\/jats:italic>\n            expression in K2966 and K2968 was dependent on PA5471, whose expression was also elevated in these mutants. Thus, mutational disruption of ribosome function, by limiting expression of ribosomal constituents, promotes recruitment of\n            <jats:italic>mexXY<\/jats:italic>\n            and does so via PA5471, reminiscent of\n            <jats:italic>mexXY<\/jats:italic>\n            induction by ribosome-disrupting antimicrobial agents. Interestingly, reduced\n            <jats:italic>rplU-rpmA<\/jats:italic>\n            expression was also observed in a\n            <jats:italic>mexXY<\/jats:italic>\n            -expressing pan-aminoglycoside-resistant clinical isolate, suggesting that ribosome-perturbing mutations have clinical relevance in the recruitment of the MexXY-OprM aminoglycoside resistance determinant.\n          <\/jats:p>","DOI":"10.1128\/aac.00846-12","type":"journal-article","created":{"date-parts":[[2012,7,24]],"date-time":"2012-07-24T04:37:37Z","timestamp":1343104657000},"page":"5171-5179","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":40,"title":["Reduced Expression of the\n            <i>rplU-rpmA<\/i>\n            Ribosomal Protein Operon in\n            <i>mexXY<\/i>\n            -Expressing Pan-Aminoglycoside-Resistant Mutants of Pseudomonas aeruginosa"],"prefix":"10.1128","volume":"56","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":"10.1128\/AAC.43.11.2624"},{"key":"e_1_3_2_3_2","doi-asserted-by":"crossref","first-page":"1714","DOI":"10.1021\/bi972280+","article-title":"Ribosomal proteins neighboring 23S rRNA nucleotides 803\u2013811 within the 50S subunit","volume":"37","author":"Alexander RW","year":"1998","unstructured":"AlexanderRW CoopermanBS. 1998. 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