{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T15:39:25Z","timestamp":1792510765319,"version":"4.5.0"},"reference-count":66,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI118257"],"award-info":[{"award-number":["R01AI118257"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI158530"],"award-info":[{"award-number":["R01AI158530"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U19AI135964"],"award-info":[{"award-number":["U19AI135964"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2026,10,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      The prevalence of non-susceptibility to ceftolozane-tazobactam (C\/T) among\n                      <jats:italic toggle=\"yes\">Pseudomonas aeruginosa<\/jats:italic>\n                      remains low, but novel mechanisms of C\/T resistance are of concern. Herein, we describe a novel\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      genotype associated with high-level C\/T resistance (&gt;256\/4 \u00b5g\/mL) in a single patient. Whole-genome sequencing of the isolate was compared to that of a susceptible isolate cultured from the same patient 2 months earlier. Analysis of the sequences revealed two different\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      high-risk clones: sequence type (ST)111 followed by ST235. The C\/T-resistant ST235 isolate contained five copies of a genetic element composed of an L2 \u03b2-lactamase gene (\n                      <jats:italic toggle=\"yes\">bla<\/jats:italic>\n                      <jats:sub>L2<\/jats:sub>\n                      ) and a truncated\n                      <jats:italic toggle=\"yes\">ampR<\/jats:italic>\n                      <jats:sub>L2<\/jats:sub>\n                      transcriptional regulator gene, which are commonly found together in\n                      <jats:italic toggle=\"yes\">Stenotrophomonas maltophilia<\/jats:italic>\n                      strains and have not been reported to mediate resistance to C\/T. Comparative genomic analysis with other\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      isolates failed to identify alternative explanations for the observed C\/T resistance. We found that exogenous expression of\n                      <jats:italic toggle=\"yes\">bla<\/jats:italic>\n                      <jats:sub>L2<\/jats:sub>\n                      increased C\/T minimum inhibitory concentrations (MICs) in genetically distinct\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      strains. A screen of our archived isolates identified two\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      clinical isolates, PS2045 and PS2046, with one and two copies, respectively, of the genetic element containing\n                      <jats:italic toggle=\"yes\">bla<\/jats:italic>\n                      <jats:sub>L2<\/jats:sub>\n                      and truncated\n                      <jats:italic toggle=\"yes\">ampR<\/jats:italic>\n                      <jats:sub>L2<\/jats:sub>\n                      . Interestingly, disruption of the gene\n                      <jats:italic toggle=\"yes\">bla<\/jats:italic>\n                      <jats:sub>L2<\/jats:sub>\n                      but not the truncated\n                      <jats:italic toggle=\"yes\">ampR<\/jats:italic>\n                      <jats:sub>L2<\/jats:sub>\n                      in PS2045 led to a decrease in C\/T MIC. Thus, we report a novel mechanism of C\/T resistance in\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      partially mediated by an L2 \u03b2-lactamase independently of its canonical regulator, AmpR\n                      <jats:sub>L2<\/jats:sub>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.00356-26","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T15:01:25Z","timestamp":1788534085000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["L2 \u03b2-lactamase contributes to ceftolozane-tazobactam resistance in\n                    <i>Pseudomonas aeruginosa<\/i>"],"prefix":"10.1128","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3713-6441","authenticated-orcid":false,"given":"Preeti","family":"Garai","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/000e0be47","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology-Immunology, Northwestern University, Feinberg School of Medicine","place":["Chicago, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0791-6340","authenticated-orcid":true,"given":"Sophia H.","family":"Nozick","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/000e0be47","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology-Immunology, Northwestern University, Feinberg School of Medicine","place":["Chicago, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline C.","family":"Jozefczyk","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00t30ch44","id-type":"ROR","asserted-by":"publisher"}],"name":"Midwestern University College of Pharmacy, Downers Grove Campus","place":["Downers Grove, USA"]},{"id":[{"id":"https:\/\/ror.org\/04fzwnh64","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pharmacy, Northwestern Medicine","place":["Chicago, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4576-287X","authenticated-orcid":true,"given":"Hannah","family":"Nam","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00f54p054","id-type":"ROR","asserted-by":"publisher"}],"name":"Stanford University School of Medicine","place":["Stanford, USA"]},{"id":[{"id":"https:\/\/ror.org\/04gyf1771","id-type":"ROR","asserted-by":"publisher"}],"name":"Infectious Diseases, University of California Irvine","place":["Orange, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5184-1385","authenticated-orcid":true,"given":"J. Nicholas","family":"O\u2019Donnell","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/014hfaw95","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pharmacy Practice, Albany College of Pharmacy and Health Sciences","place":["Albany, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7131-3691","authenticated-orcid":true,"given":"Egon A.","family":"Ozer","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/000e0be47","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Infectious Diseases, Department of Medicine, Northwestern University, Feinberg School of Medicine","place":["Chicago, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4596-7939","authenticated-orcid":true,"given":"Alan R.","family":"Hauser","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/000e0be47","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology-Immunology, Northwestern University, Feinberg School of Medicine","place":["Chicago, USA"]},{"id":[{"id":"https:\/\/ror.org\/000e0be47","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Infectious Diseases, Department of Medicine, Northwestern University, Feinberg School of Medicine","place":["Chicago, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0018-5434","authenticated-orcid":true,"given":"Nathaniel J.","family":"Rhodes","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04fzwnh64","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pharmacy, Northwestern Medicine","place":["Chicago, USA"]},{"id":[{"id":"https:\/\/ror.org\/00t30ch44","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pharmacy Practice, Midwestern University College of Pharmacy Downers Grove Campus","place":["Downers Grove, USA"]},{"id":[{"id":"https:\/\/ror.org\/00t30ch44","id-type":"ROR","asserted-by":"publisher"}],"name":"Pharmacometrics Center of Excellence, Midwestern University College of Pharmacy, Downers Grove Campus","place":["Downers Grove, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/phar.1609"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-013-0168-2"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1080\/14787210.2018.1447381"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cix182"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(19)30403-7"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2018.11.001"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00834-09"},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2021.09.064"},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00465-17"},{"key":"e_1_3_6_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciab295"},{"key":"e_1_3_6_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2009.03.021"},{"key":"e_1_3_6_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciw243"},{"key":"e_1_3_6_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2025.09.015"},{"key":"e_1_3_6_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02462-13"},{"key":"e_1_3_6_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01117-20"},{"key":"e_1_3_6_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofab311"},{"key":"e_1_3_6_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00825-15"},{"key":"e_1_3_6_19_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.1007162"},{"key":"e_1_3_6_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkx424"},{"key":"e_1_3_6_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01117-17"},{"key":"e_1_3_6_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00089-21"},{"key":"e_1_3_6_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01183-17"},{"key":"e_1_3_6_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(24)00648-0"},{"key":"e_1_3_6_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2007.521"},{"key":"e_1_3_6_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1183-784"},{"key":"e_1_3_6_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.05087-22"},{"key":"e_1_3_6_28_2","doi-asserted-by":"publisher","DOI":"10.21105\/joss.01762"},{"key":"e_1_3_6_29_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2009.07027.x"},{"key":"e_1_3_6_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0378-1119(98)00130-9"},{"key":"e_1_3_6_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.7.1460"},{"key":"e_1_3_6_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01718-18"},{"key":"e_1_3_6_33_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkz149"},{"key":"e_1_3_6_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0092-8674(00)81928-5"},{"key":"e_1_3_6_35_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1994.0138"},{"key":"e_1_3_6_36_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1348-0421.1992.tb02109.x"},{"key":"e_1_3_6_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.40.5.1254"},{"key":"e_1_3_6_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01485-07"},{"key":"e_1_3_6_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00341-08"},{"key":"e_1_3_6_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2014.01.032"},{"key":"e_1_3_6_41_2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofy158"},{"key":"e_1_3_6_42_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02688-16"},{"key":"e_1_3_6_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.resmic.2008.11.001"},{"key":"e_1_3_6_44_2","doi-asserted-by":"publisher","DOI":"10.1099\/00207713-43-3-606"},{"key":"e_1_3_6_45_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0007740"},{"key":"e_1_3_6_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)61137-5"},{"key":"e_1_3_6_47_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01660-10"},{"key":"e_1_3_6_48_2","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.13831"},{"key":"e_1_3_6_49_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.33.8.1268"},{"key":"e_1_3_6_50_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/40.5.717"},{"key":"e_1_3_6_51_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/37.2.394"},{"key":"e_1_3_6_52_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01110-19"},{"key":"e_1_3_6_53_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkaa291"},{"key":"e_1_3_6_54_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01637-19"},{"key":"e_1_3_6_55_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-018-3361-0"},{"key":"e_1_3_6_56_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21031026"},{"key":"e_1_3_6_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2021.106278"},{"key":"e_1_3_6_58_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01809-18"},{"key":"e_1_3_6_59_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00084-21"},{"key":"e_1_3_6_60_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02067-21"},{"key":"e_1_3_6_61_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaa1306"},{"key":"e_1_3_6_62_2","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics11020130"},{"key":"e_1_3_6_63_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12866-025-03935-3"},{"key":"e_1_3_6_64_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01970-17"},{"key":"e_1_3_6_65_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0266742"},{"key":"e_1_3_6_66_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01252-13"},{"key":"e_1_3_6_67_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02461-20"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.00356-26","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.00356-26","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T14:49:40Z","timestamp":1792507780000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.00356-26"}},"subtitle":[],"editor":[{"given":"Alita A.","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,10,7]]},"references-count":66,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10,7]]}},"alternative-id":["10.1128\/aac.00356-26"],"URL":"https:\/\/doi.org\/10.1128\/aac.00356-26","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,7]]},"assertion":[{"value":"2026-03-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00356-26"}}