{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T20:02:39Z","timestamp":1792526559201,"version":"4.5.0"},"reference-count":51,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2009,6,1]],"date-time":"2009-06-01T00:00:00Z","timestamp":1243814400000},"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":[[2009,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The overproduction of chromosomal AmpC \u03b2-lactamase poses a serious challenge to the successful treatment of\n            <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n            infections with \u03b2-lactam antibiotics. The induction of\n            <jats:italic>ampC<\/jats:italic>\n            expression by \u03b2-lactams is mediated by the disruption of peptidoglycan (PG) recycling and the accumulation of cytosolic 1,6-anhydro-\n            <jats:italic>N<\/jats:italic>\n            -acetylmuramyl peptides, catabolites of PG recycling that are generated by an\n            <jats:italic>N<\/jats:italic>\n            -acetyl-\u03b2-\n            <jats:sc>d<\/jats:sc>\n            -glucosaminidase encoded by\n            <jats:italic>nagZ<\/jats:italic>\n            (PA3005). In the absence of \u03b2-lactams,\n            <jats:italic>ampC<\/jats:italic>\n            expression is repressed by three AmpD amidases encoded by\n            <jats:italic>ampD<\/jats:italic>\n            ,\n            <jats:italic>ampDh2<\/jats:italic>\n            , and\n            <jats:italic>ampDh3<\/jats:italic>\n            , which act to degrade these 1,6-anhydro-\n            <jats:italic>N<\/jats:italic>\n            -acetylmuramyl peptide inducer molecules. The inactivation of\n            <jats:italic>ampD<\/jats:italic>\n            genes results in the stepwise upregulation of\n            <jats:italic>ampC<\/jats:italic>\n            expression and clinical resistance to antipseudomonal \u03b2-lactams due to the accumulation of the\n            <jats:italic>ampC<\/jats:italic>\n            inducer anhydromuropeptides. To examine the role of NagZ on AmpC-mediated \u03b2-lactam resistance in\n            <jats:italic>P. aeruginosa<\/jats:italic>\n            , we inactivated\n            <jats:italic>nagZ<\/jats:italic>\n            in\n            <jats:italic>P. aeruginosa<\/jats:italic>\n            PAO1 and in an isogenic triple\n            <jats:italic>ampD<\/jats:italic>\n            null mutant. We show that the inactivation of\n            <jats:italic>nagZ<\/jats:italic>\n            represses both the intrinsic \u03b2-lactam resistance (up to 4-fold) and the high antipseudomonal \u03b2-lactam resistance (up to 16-fold) that is associated with the loss of AmpD activity. We also demonstrate that AmpC-mediated resistance to antipseudomonal \u03b2-lactams can be attenuated in PAO1 and in a series of\n            <jats:italic>ampD<\/jats:italic>\n            null mutants using a selective small-molecule inhibitor of NagZ. Our results suggest that the blockage of NagZ activity could provide a strategy to enhance the efficacies of \u03b2-lactams against\n            <jats:italic>P. aeruginosa<\/jats:italic>\n            and other gram-negative organisms that encode inducible chromosomal\n            <jats:italic>ampC<\/jats:italic>\n            and to counteract the hyperinduction of\n            <jats:italic>ampC<\/jats:italic>\n            that occurs from the selection of\n            <jats:italic>ampD<\/jats:italic>\n            null mutations during \u03b2-lactam therapy.\n          <\/jats:p>","DOI":"10.1128\/aac.01617-08","type":"journal-article","created":{"date-parts":[[2009,3,10]],"date-time":"2009-03-10T01:23:34Z","timestamp":1236648214000},"page":"2274-2282","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":71,"title":["Inactivation of the Glycoside Hydrolase NagZ Attenuates Antipseudomonal \u03b2-Lactam Resistance in\n            <i>Pseudomonas aeruginosa<\/i>"],"prefix":"10.1128","volume":"53","author":[{"given":"Azizah","family":"Asgarali","sequence":"first","affiliation":[{"name":"Department of Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada R3T 2N2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith A.","family":"Stubbs","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Simon Fraser University, 8888 University Drive, Burnaby, British Columbia, Canada V5A 1S6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Oliver","sequence":"additional","affiliation":[{"name":"Servicio de Microbiologi\u0301a, Hospital Son Dureta, Palma de Mallorca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Vocadlo","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Simon Fraser University, 8888 University Drive, Burnaby, British Columbia, Canada V5A 1S6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian L.","family":"Mark","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada R3T 2N2"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.46.11.3406-3411.2002"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1991.tb01920.x"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.182.17.4836-4840.2000"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.184.23.6434-6436.2002"},{"key":"e_1_3_2_6_2","unstructured":"Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically 2003"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.40.9.2173"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.10.2113"},{"key":"e_1_3_2_9_2","doi-asserted-by":"crossref","first-page":"6560","DOI":"10.1073\/pnas.0711491105","volume":"105","year":"2008","unstructured":"Ficko-Blean, E., K. 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