{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:51:14Z","timestamp":1791298274685,"version":"4.1.0"},"reference-count":41,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2010,9,1]],"date-time":"2010-09-01T00:00:00Z","timestamp":1283299200000},"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":[[2010,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    AmpC hyperproduction is the most frequent mechanism of resistance to penicillins and cephalosporins in\n                    <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                    and is driven by\n                    <jats:italic>ampD<\/jats:italic>\n                    mutations or the recently described inactivation of\n                    <jats:italic>dacB<\/jats:italic>\n                    , which encodes the nonessential penicillin-binding protein (PBP) PBP 4. Recent work showed that\n                    <jats:italic>nagZ<\/jats:italic>\n                    inactivation attenuates \u03b2-lactam resistance in\n                    <jats:italic>ampD<\/jats:italic>\n                    mutants. Here we explored whether the same could be true for the\n                    <jats:italic>dacB<\/jats:italic>\n                    mutants with\n                    <jats:italic>dacB<\/jats:italic>\n                    mutations alone or in combination with\n                    <jats:italic>ampD<\/jats:italic>\n                    mutations. The inactivation of\n                    <jats:italic>nagZ<\/jats:italic>\n                    restored the wild-type \u03b2-lactam MICs and\n                    <jats:italic>ampC<\/jats:italic>\n                    expression of PAO1\n                    <jats:italic>dacB<\/jats:italic>\n                    and\n                    <jats:italic>ampD<\/jats:italic>\n                    mutants and dramatically reduced the MICs (for example, the MIC for ceftazidime dropped from 96 to 4 \u03bcg\/ml) and the level of\n                    <jats:italic>ampC<\/jats:italic>\n                    expression (from ca. 1,000-fold to ca. 50-fold higher than that for PAO1) in the\n                    <jats:italic>dacB<\/jats:italic>\n                    -\n                    <jats:italic>ampD<\/jats:italic>\n                    double mutant. On the other hand,\n                    <jats:italic>nagZ<\/jats:italic>\n                    inactivation had little effect on the inducibility of AmpC. The NagZ inhibitor\n                    <jats:italic>O<\/jats:italic>\n                    -(2-acetamido-2-deoxy-\n                    <jats:sc>d<\/jats:sc>\n                    -glucopyranosylidene)amino-\n                    <jats:italic>N<\/jats:italic>\n                    -phenylcarbamate attenuated the \u03b2-lactam resistance of the AmpC-hyperproducing strains, showing a greater effect on the\n                    <jats:italic>dacB<\/jats:italic>\n                    mutant (reducing the ceftazidime MICs from 24 to 6 \u03bcg\/ml) than the\n                    <jats:italic>ampD<\/jats:italic>\n                    mutant (reducing the MICs from 8 to 4 \u03bcg\/ml). Additionally,\n                    <jats:italic>nagZ<\/jats:italic>\n                    inactivation in the\n                    <jats:italic>dacB<\/jats:italic>\n                    mutant blocked the overexpression of\n                    <jats:italic>creD<\/jats:italic>\n                    (\n                    <jats:italic>blrD<\/jats:italic>\n                    ), which is a marker of the activation of the CreBC (BlrAB) regulator involved in the resistance phenotype. Finally, through population analysis, we show that the inactivation of\n                    <jats:italic>nagZ<\/jats:italic>\n                    dramatically reduces the capacity of\n                    <jats:italic>P. aeruginosa<\/jats:italic>\n                    to develop ceftazidime resistance, since spontaneous mutants were not obtained at concentrations \u22658 \u03bcg\/ml (the susceptibility breakpoint) for the\n                    <jats:italic>nagZ<\/jats:italic>\n                    mutant but were obtained with wild-type PAO1. Therefore, NagZ is envisaged to be a candidate target for preventing and reverting \u03b2-lactam resistance in\n                    <jats:italic>P. aeruginosa<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1128\/aac.00385-10","type":"journal-article","created":{"date-parts":[[2010,6,21]],"date-time":"2010-06-21T22:41:31Z","timestamp":1277160091000},"page":"3557-3563","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":71,"title":["NagZ Inactivation Prevents and Reverts \u03b2-Lactam Resistance, Driven by AmpD and PBP 4 Mutations, in\n                    <i>Pseudomonas aeruginosa<\/i>"],"prefix":"10.1128","volume":"54","author":[{"given":"Laura","family":"Zamorano","sequence":"first","affiliation":[{"name":"Servicio de Microbiologi\u0301a and Unidad de Investigacio\u0301n, Instituto Universitario de Investigacio\u0301n en Ciencias de la Salud (IUNICS), Palma de Mallorca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas M.","family":"Reeve","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lehua","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Simon Fraser University, Burnaby, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Juan","sequence":"additional","affiliation":[{"name":"Servicio de Microbiologi\u0301a and Unidad de Investigacio\u0301n, Instituto Universitario de Investigacio\u0301n en Ciencias de la Salud (IUNICS), Palma de Mallorca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bartolome\u0301","family":"Moya\u0301","sequence":"additional","affiliation":[{"name":"Servicio de Microbiologi\u0301a and Unidad de Investigacio\u0301n, Instituto Universitario de Investigacio\u0301n en Ciencias de la Salud (IUNICS), Palma de Mallorca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Cabot","sequence":"additional","affiliation":[{"name":"Servicio de Microbiologi\u0301a and Unidad de Investigacio\u0301n, Instituto Universitario de Investigacio\u0301n en Ciencias de la Salud (IUNICS), Palma de Mallorca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Vocadlo","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Simon Fraser University, Burnaby, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian L.","family":"Mark","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Oliver","sequence":"additional","affiliation":[{"name":"Servicio de Microbiologi\u0301a and Unidad de Investigacio\u0301n, Instituto Universitario de Investigacio\u0301n en Ciencias de la Salud (IUNICS), Palma de Mallorca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","first-page":"2006","volume":"179","year":"1996","unstructured":"Alksne, L. 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