{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T22:45:24Z","timestamp":1793313924004,"version":"4.5.0"},"reference-count":47,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2015,7,1]],"date-time":"2015-07-01T00:00:00Z","timestamp":1435708800000},"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":[[2015,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            This study aimed to characterize the role 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            low-molecular-mass penicillin-binding proteins (LMM PBPs), namely, PBP4 (DacB), PBP5 (DacC), and PBP7 (PbpG), in peptidoglycan composition, \u03b2-lactam resistance, and\n            <jats:italic>ampC<\/jats:italic>\n            regulation. For this purpose, we constructed all single and multiple mutants of\n            <jats:italic>dacB<\/jats:italic>\n            ,\n            <jats:italic>dacC<\/jats:italic>\n            ,\n            <jats:italic>pbpG<\/jats:italic>\n            , and\n            <jats:italic>ampC<\/jats:italic>\n            from the 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 strain. Peptidoglycan composition was determined by high-performance liquid chromatography (HPLC),\n            <jats:italic>ampC<\/jats:italic>\n            expression by reverse transcription-PCR (RT-PCR), PBP patterns by a Bocillin FL-binding test, and antimicrobial susceptibility by MIC testing for a panel of \u03b2-lactams. Microscopy and growth rate analyses revealed no apparent major morphological changes for any of the mutants compared to the wild-type PAO1 strain. Of the single mutants, only\n            <jats:italic>dacC<\/jats:italic>\n            mutation led to significantly increased pentapeptide levels, showing that PBP5 is the major\n            <jats:sc>dd<\/jats:sc>\n            -carboxypeptidase in\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            . Moreover, our results indicate that PBP4 and PBP7 play a significant role as\n            <jats:sc>dd<\/jats:sc>\n            -carboxypeptidase only if PBP5 is absent, and their\n            <jats:sc>dd<\/jats:sc>\n            -endopeptidase activity is also inferred. As expected, the inactivation of PBP4 led to a significant increase in\n            <jats:italic>ampC<\/jats:italic>\n            expression (around 50-fold), but, remarkably, the sequential inactivation of the three LMM PBPs produced a much greater increase (1,000-fold), which correlated with peptidoglycan pentapeptide levels. Finally, the \u03b2-lactam susceptibility profiles of the LMM PBP mutants correlated well with the\n            <jats:italic>ampC<\/jats:italic>\n            expression data. However, the inactivation of\n            <jats:italic>ampC<\/jats:italic>\n            in these mutants also evidenced a role of LMM PBPs, especially PBP5, in intrinsic \u03b2-lactam resistance. In summary, in addition to assessing the effect 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            LMM PBPs on peptidoglycan structure for the first time, we obtained results that represent a step forward in understanding the impact of these PBPs on \u03b2-lactam resistance, apparently driven by the interplay between their roles in AmpC induction, \u03b2-lactam trapping, and\n            <jats:sc>dd<\/jats:sc>\n            -carboxypeptidase\/\u03b2-lactamase activity.\n          <\/jats:p>","DOI":"10.1128\/aac.05150-14","type":"journal-article","created":{"date-parts":[[2015,4,21]],"date-time":"2015-04-21T02:31:49Z","timestamp":1429583509000},"page":"3925-3934","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":82,"title":["Role of Pseudomonas aeruginosa Low-Molecular-Mass Penicillin-Binding Proteins in AmpC Expression, \u03b2-Lactam Resistance, and Peptidoglycan Structure"],"prefix":"10.1128","volume":"59","author":[{"given":"Alaa","family":"Ropy","sequence":"first","affiliation":[{"name":"Centro de Biolog\u00eda Molecular Severo Ochoa, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Cabot","sequence":"additional","affiliation":[{"name":"Servicio de Microbiolog\u00eda and Unidad de Investigaci\u00f3n, Hospital Universitario Son Espases, Instituto de Investigaci\u00f3n Sanitaria de Palma (IdISPa), Palma de Mallorca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"S\u00e1nchez-Diener","sequence":"additional","affiliation":[{"name":"Servicio de Microbiolog\u00eda and Unidad de Investigaci\u00f3n, Hospital Universitario Son Espases, Instituto de Investigaci\u00f3n Sanitaria de Palma (IdISPa), Palma de Mallorca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristian","family":"Aguilera","sequence":"additional","affiliation":[{"name":"Centro de Biolog\u00eda Molecular Severo Ochoa, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bartolome","family":"Moya","sequence":"additional","affiliation":[{"name":"Servicio de Microbiolog\u00eda and Unidad de Investigaci\u00f3n, Hospital Universitario Son Espases, Instituto de Investigaci\u00f3n Sanitaria de Palma (IdISPa), Palma de Mallorca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan A.","family":"Ayala","sequence":"additional","affiliation":[{"name":"Centro de Biolog\u00eda Molecular Severo Ochoa, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Oliver","sequence":"additional","affiliation":[{"name":"Servicio de Microbiolog\u00eda and Unidad de Investigaci\u00f3n, Hospital Universitario Son Espases, Instituto de 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