{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T01:07:35Z","timestamp":1791248855488,"version":"4.1.0"},"reference-count":47,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2011,5,1]],"date-time":"2011-05-01T00:00:00Z","timestamp":1304208000000},"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":[[2011,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The adaptive resistance of\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            to aminoglycosides is known to occur during chronic lung infections in cystic fibrosis patients in response to nonlethal concentrations of aminoglycosides. Not only is it difficult to achieve high levels of drug throughout the dehydrated mucus in the lung, but also steep oxygen gradients exist across the mucus layer, further reducing the bactericidal activity of aminoglycosides. In this study, microarray analysis was utilized to examine the gene responses 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            to lethal, inhibitory, and subinhibitory concentrations of tobramycin under aerobic and anaerobic conditions. While prolonged exposure to subinhibitory concentrations of tobramycin caused increased levels of expression predominantly of the efflux pump genes\n            <jats:italic>mexXY<\/jats:italic>\n            , the greatest increases in gene expression levels in response to lethal concentrations of tobramycin involved a number of heat shock genes and the PA0779 gene (renamed here\n            <jats:italic>asrA<\/jats:italic>\n            ), encoding an alternate Lon protease. Microarray analysis of an\n            <jats:italic>asrA<\/jats:italic>\n            ::\n            <jats:italic>luxCDABE<\/jats:italic>\n            transposon mutant revealed that the induction of heat shock genes in response to tobramycin in this mutant was significantly decreased compared to that in the parent strain. The level of expression of\n            <jats:italic>asrA<\/jats:italic>\n            was induced from an arabinose-inducible promoter to 35-fold greater than wild-type expression levels in the absence of tobramycin, and this overexpression alone caused an increased expression of the heat shock genes, as determined by quantitative PCR (qPCR). This overexpression of\n            <jats:italic>asrA<\/jats:italic>\n            conferred short-term protection against lethal levels (4 \u03bcg\/ml) of tobramycin but did not affect the tobramycin MIC. The RpoH heat shock sigma factor was found to be involved in the regulation of\n            <jats:italic>asrA<\/jats:italic>\n            in response to both heat shock and tobramycin at the posttranscriptional level. The results of this work suggest that the tobramycin concentration has a significant impact on the gene expression 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            , with lethal concentrations resulting in immediate adaptations conferring short-term protection, such as the induction of the heat shock response, and with subinhibitory concentrations leading to more sustainable long-term protection mechanisms, such as increased efflux.\n          <\/jats:p>","DOI":"10.1128\/aac.00935-10","type":"journal-article","created":{"date-parts":[[2011,3,1]],"date-time":"2011-03-01T23:32:24Z","timestamp":1299022344000},"page":"1874-1882","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":77,"title":["Involvement of an ATP-Dependent Protease, PA0779\/AsrA, in Inducing Heat Shock in Response to Tobramycin in Pseudomonas aeruginosa"],"prefix":"10.1128","volume":"55","author":[{"given":"Kristen N.","family":"Kindrachuk","sequence":"first","affiliation":[{"name":"Centre for Microbial Diseases and Immunity Research, University of British Columbia, 2259 Lower Mall, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc\u00eda","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Centre for Microbial Diseases and Immunity Research, University of British Columbia, 2259 Lower Mall, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manjeet","family":"Bains","sequence":"additional","affiliation":[{"name":"Centre for Microbial Diseases and Immunity Research, University of British Columbia, 2259 Lower Mall, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert E. 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