{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T03:46:25Z","timestamp":1775533585834,"version":"3.50.1"},"reference-count":41,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2024,5,2]],"date-time":"2024-05-02T00:00:00Z","timestamp":1714608000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,5,2]],"date-time":"2024-05-02T00:00:00Z","timestamp":1714608000000},"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":[[2024,5,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              We subjected seven\n              <jats:italic>P<\/jats:italic>\n              .\n              <jats:italic>aeruginosa<\/jats:italic>\n              isolates to a 10-day serial passaging against five antipseudomonal agents to evaluate resistance levels post-exposure and putative resistance mechanisms in terminal mutants were analyzed by whole-genome sequencing analysis. Meropenem (mean, 38-fold increase), cefepime (14.4-fold), and piperacillin-tazobactam (52.9-fold) terminal mutants displayed high minimum inhibitory concentration (MIC) values compared to those obtained after exposure to ceftolozane-tazobactam (11.4-fold) and ceftazidime-avibactam (5.7-fold). Fewer isolates developed elevated MIC values for other \u03b2-lactams and agents belonging to other classes when exposed to meropenem in comparison to other agents. Alterations in\n              <jats:italic>nalC<\/jats:italic>\n              and\n              <jats:italic>nalD,<\/jats:italic>\n              involved in the upregulation of the efflux pump system MexAB-OprM, were common and observed more frequently in isolates exposed to ceftazidime-avibactam and meropenem. These alterations, along with ones in\n              <jats:italic>mexR<\/jats:italic>\n              and\n              <jats:italic>amrR,<\/jats:italic>\n              provided resistance to most \u03b2-lactams and levofloxacin but not imipenem. The second most common gene altered was\n              <jats:italic>mpl,<\/jats:italic>\n              which is involved in the recycling of the cell wall peptidoglycan. These alterations were mainly noted in isolates exposed to ceftolozane-tazobactam and piperacillin-tazobactam but also in one cefepime-exposed isolate. Alterations in other genes known to be involved in \u03b2-lactam resistance (\n              <jats:italic>ftsI<\/jats:italic>\n              ,\n              <jats:italic>oprD<\/jats:italic>\n              ,\n              <jats:italic>phoP, pepA,<\/jats:italic>\n              and\n              <jats:italic>cplA<\/jats:italic>\n              ) and multiple genes involved in lipopolysaccharide biosynthesis were also present. The data generated here suggest that there is a difference in the mechanisms selected for high-level resistance between newer \u03b2-lactam\/\u03b2-lactamase inhibitor combinations and older agents. Nevertheless, the isolates exposed to all agents displayed elevated MIC values for other \u03b2-lactams (except imipenem) and quinolones tested mainly due to alterations in the MexAB-OprM regulators that extrude these agents.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.01363-23","type":"journal-article","created":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T12:45:39Z","timestamp":1711370739000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":10,"title":["<i>In vitro<\/i>\n            development of resistance against antipseudomonal agents: comparison of novel \u03b2-lactam\/\u03b2-lactamase inhibitor combinations and other \u03b2-lactam agents"],"prefix":"10.1128","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0126-1782","authenticated-orcid":true,"given":"Mariana","family":"Castanheira","sequence":"first","affiliation":[{"name":"JMI Laboratories, North Liberty, Iowa, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0457-1543","authenticated-orcid":false,"given":"John H.","family":"Kimbrough","sequence":"additional","affiliation":[{"name":"JMI Laboratories, North Liberty, Iowa, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jill","family":"Lindley","sequence":"additional","affiliation":[{"name":"JMI Laboratories, North Liberty, Iowa, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy B.","family":"Doyle","sequence":"additional","affiliation":[{"name":"JMI Laboratories, North Liberty, Iowa, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica M.","family":"Ewald","sequence":"additional","affiliation":[{"name":"JMI Laboratories, North Liberty, Iowa, USA"},{"name":"The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7022-6644","authenticated-orcid":true,"given":"Helio S.","family":"Sader","sequence":"additional","affiliation":[{"name":"JMI Laboratories, North Liberty, Iowa, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00040-09"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2011.03570.x"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofy343"},{"key":"e_1_3_2_5_2","unstructured":"Prevention CDC. 2019. Pseudomonas aeruginosa in healthcare settings. Available from: https:\/\/www.cdc.gov\/hai\/organisms\/pseudomonas.html"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics9090632"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1177\/1060028020974003"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00115-20"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00894-20"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02067-21"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkaa291"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02085-18"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.04238-14"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.03681-14"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02461-20"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkz243"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00089-21"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkaa396"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02112-19"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01117-17"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1996.1351503.x"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.201000212"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0017624"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msaa233"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.200800618"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00355-19"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.44.12.3322-3327.2000"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgar.2022.07.021"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01117-20"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.03057-14"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.50.5.1780-1787.2006"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01379-18"},{"key":"e_1_3_2_33_2","volume-title":"M07","author":"CLSI","year":"2018","unstructured":"CLSI. 2018. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. In M07, 11th ed. Clinical and Laboratory Standards Institute, Wayne, PA.","edition":"11"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1005595"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1089\/cmb.2012.0021"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.2289704"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.107524.110"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr509"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2004-5-2-r12"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu153"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.4161\/fly.19695"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01363-23","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01363-23","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,2]],"date-time":"2024-05-02T13:01:27Z","timestamp":1714654887000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.01363-23"}},"subtitle":[],"editor":[{"given":"Alessandra","family":"Carattoli","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2024,5,2]]},"references-count":41,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,5,2]]}},"alternative-id":["10.1128\/aac.01363-23"],"URL":"https:\/\/doi.org\/10.1128\/aac.01363-23","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,2]]},"assertion":[{"value":"2023-10-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01363-23"}}