{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T09:21:50Z","timestamp":1787649710543,"version":"build-2736575974"},"reference-count":19,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"vor","delay-in-days":21,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005869","name":"University of Fribourg","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005869","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000741","name":"NARA","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000741","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002329","name":"Federal Office of Public Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002329","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The class C \u03b2-lactamase, PAC-1, was originally described as acquired in Pseudomonas aeruginosa clinical isolates from south Asia, the corresponding gene being chromosomally located and embedded within a Tn1721-like transposon. Despite its association with high-level resistance to cephalosporins and \u03b2-lactam\/\u03b2-lactamase inhibitor combinations, data on its full hydrolytic profile and kinetic parameters have not yet been comprehensively characterized.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To characterize the susceptibility profile and hydrolytic kinetics of PAC-1, with a particular focus on cefiderocol hydrolysis, and the activity of novel \u03b2-lactam\/\u03b2-lactamase inhibitor combinations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The blaPAC-1 allele was cloned into vector pUCP24 and expressed in Escherichia coli TOP10 and Pseudomonas aeruginosa PAO1, respectively. MICs were determined by broth microdilution and interpreted according to EUCAST guidelines. PAC-1 was purified, and steady-state kinetic measurements of selected \u03b2-lactams were determined. IC50 values were determined for the \u03b2-lactamase inhibitors avibactam, taniborbactam, xeruborbactam and zidebactam. WGS was performed to characterize the genetic environment of the blaPAC-1 gene.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>PAC-1 conferred broad resistance to penicillins, broad-spectrum cephalosporins and cefiderocol, while carbapenems remained unaffected. Kinetic analyses confirmed high catalytic efficiency against cefotaxime and aztreonam, but no hydrolysis of imipenem. Avibactam, relebactam and vaborbactam failed to inhibit PAC-1 (IC50\u200a&amp;gt;\u200a1000\u2005\u00b5M), whereas xeruborbactam and zidebactam showed potent inhibitory activities (IC50\u200a=\u200a1.0 and 0.6\u2005\u00b5M, respectively). A chromosomally located Tn1721-like transposon was identified carrying the blaPAC-1 gene in P. aeruginosa ST4936.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>PAC-1 is not inhibited by avibactam and hydrolyses a broad range of \u03b2-lactams including the novel cephalosporin cefiderocol. The combination cefiderocol\/zidebactam was the most active against PAC-1. Transposon-mediated dissemination across distinct lineages warrants continued epidemiological surveillance of PAC-type \u03b2-lactamases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkag291","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T11:41:57Z","timestamp":1786448517000},"source":"Crossref","is-referenced-by-count":0,"title":["Phenotypic and biochemical characterization of the class C \u03b2-lactamase, PAC-1"],"prefix":"10.1093","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7374-0788","authenticated-orcid":false,"given":"Ot\u00e1vio Hallal Ferreira","family":"Raro","sequence":"first","affiliation":[{"name":"Medical and Molecular Microbiology Unit\u2014Department of Oncology, Microbiology, Immunology (OMI), Faculty of Science and Medicine, University of Fribourg , Chemin du Mus\u00e9e 18, Fribourg CH-1700 ,","place":["Switzerland"]},{"name":"Swiss National Reference Center for Emerging Antibiotic Resistance (NARA), Faculty of Science and Medicine, University of Fribourg , Fribourg ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Mancini","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology, University of Zurich , Zurich ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7335-9001","authenticated-orcid":false,"given":"Jacqueline","family":"Findlay","sequence":"additional","affiliation":[{"name":"Medical and Molecular Microbiology Unit\u2014Department of Oncology, Microbiology, Immunology (OMI), Faculty of Science and Medicine, University of Fribourg , Chemin du Mus\u00e9e 18, Fribourg CH-1700 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena M B","family":"Seth-Smith","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology, University of Zurich , Zurich ,","place":["Switzerland"]},{"name":"SIB Swiss Institute of Bioinformatics , Zurich ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Ali Syed","sequence":"additional","affiliation":[{"name":"Department of Microbiology, The University of Haripur , Haripur ,","place":["Pakistan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3564-8603","authenticated-orcid":false,"given":"Adrian","family":"Egli","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology, University of Zurich , Zurich ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1343-1622","authenticated-orcid":false,"given":"Patrice","family":"Nordmann","sequence":"additional","affiliation":[{"name":"Medical and Molecular Microbiology Unit\u2014Department of Oncology, Microbiology, Immunology (OMI), Faculty of Science and Medicine, University of Fribourg , Chemin du Mus\u00e9e 18, Fribourg CH-1700 ,","place":["Switzerland"]},{"name":"Swiss National Reference Center for Emerging Antibiotic Resistance (NARA), Faculty of Science and Medicine, University of Fribourg , Fribourg ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5160-5286","authenticated-orcid":false,"given":"Laurent","family":"Poirel","sequence":"additional","affiliation":[{"name":"Medical and Molecular Microbiology Unit\u2014Department of Oncology, Microbiology, Immunology (OMI), Faculty of Science and Medicine, University of Fribourg , Chemin du Mus\u00e9e 18, Fribourg CH-1700 ,","place":["Switzerland"]},{"name":"Swiss National Reference Center for Emerging Antibiotic Resistance (NARA), Faculty of Science and Medicine, University of Fribourg , Fribourg ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,8,25]]},"reference":[{"key":"2026082504494312100_dkag291-B1","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1128\/AAC.03954-14","article-title":"The resistome of Pseudomonas aeruginosa in relationship to phenotypic susceptibility","volume":"59","author":"Kos","year":"2015","journal-title":"Antimicrob Agents Chemother"},{"key":"2026082504494312100_dkag291-B2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00694-17","article-title":"Pseudomonas aeruginosa clinical isolates in Nepal coproducing metallo-\u03b2-lactamases and 16S rRNA methyltransferases","volume":"61","author":"Tada","year":"2017","journal-title":"Antimicrob Agents Chemother"},{"key":"2026082504494312100_dkag291-B3","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01375-19","article-title":"Acquisition of class C \u03b2-lactamase PAC-1 by ST664 strains of Pseudomonas aeruginosa","volume":"63","author":"Bour","year":"2019","journal-title":"Antimicrob Agents Chemother"},{"key":"2026082504494312100_dkag291-B4","doi-asserted-by":"publisher","first-page":"1706","DOI":"10.1080\/22221751.2021.1968318","article-title":"Genomic characterization of carbapenem-non-susceptible Pseudomonas aeruginosa in Singapore","volume":"10","author":"Teo","year":"2021","journal-title":"Emerg Microbes Infect"},{"key":"2026082504494312100_dkag291-B5","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.01391-23","article-title":"First report of environmental blaPAC-1-carrying Aeromonas enteropelogenes","volume":"11","author":"Zhong","year":"2023","journal-title":"Microbiol Spectr"},{"key":"2026082504494312100_dkag291-B6","doi-asserted-by":"publisher","DOI":"10.1093\/jacamr\/dlaf129","article-title":"Cefepime-zidebactam therapy for extensively drug-resistant Pseudomonas aeruginosa and Klebsiella pneumoniae infection as a bridge to liver transplantation","volume":"7","author":"Tsai","year":"2025","journal-title":"JAC Antimicrob Resist"},{"key":"2026082504494312100_dkag291-B7","doi-asserted-by":"publisher","first-page":"2799","DOI":"10.1093\/jac\/dkaf301","article-title":"Performance of disc diffusion and gradient strip test on different Mueller-Hinton agar media plates and ComASP\u00ae and Bruker UMIC\u00ae cefiderocol microdilution panels for cefiderocol susceptibility testing in carbapenem-resistant Pseudomonas aeruginosa","volume":"80","author":"Mancini","year":"2025","journal-title":"J Antimicrob Chemother"},{"key":"2026082504494312100_dkag291-B8","doi-asserted-by":"publisher","first-page":"576","DOI":"10.3390\/vetsci12060576","article-title":"Companion animals as reservoirs of multidrug resistance\u2014a rare case of an XDR, NDM-1-producing Pseudomonas aeruginosa strain of feline origin in Greece","volume":"12","author":"Lysitsas","year":"2025","journal-title":"Vet Sci"},{"key":"2026082504494312100_dkag291-B9","author":"Saavedra"},{"key":"2026082504494312100_dkag291-B10","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.01805-25","article-title":"Emergence and dissemination of blaKPC-31 and blaPAC-2 among different species of Enterobacterales in Colombia: a new challenge for the microbiological laboratories","volume":"13","author":"Castro","year":"2025","journal-title":"Microbiol Spectr"},{"key":"2026082504494312100_dkag291-B11","doi-asserted-by":"publisher","DOI":"10.1128\/cmr.00150-21","article-title":"Class C \u03b2-lactamases: molecular characteristics","volume":"35","author":"Philippon","year":"2022","journal-title":"Clin Microbiol Rev"},{"key":"2026082504494312100_dkag291-B12","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/0378-1119(94)90237-2","article-title":"Construction of improved Escherichia-Pseudomonas shuttle vectors derived from pUC18\/19 and sequence of the region required for their replication in Pseudomonas aeruginosa","volume":"148","author":"West","year":"1994","journal-title":"Gene"},{"key":"2026082504494312100_dkag291-B13","author":"EUCAST"},{"key":"2026082504494312100_dkag291-B14","doi-asserted-by":"publisher","first-page":"e45","DOI":"10.1093\/nar\/gkm047","article-title":"A versatile ligation-independent cloning method suitable for high-throughput expression screening applications","volume":"35","author":"Berrow","year":"2007","journal-title":"Nucleic Acids Res"},{"key":"2026082504494312100_dkag291-B15","doi-asserted-by":"publisher","first-page":"E3745","DOI":"10.1073\/pnas.1601368113","article-title":"Cross-class metallo-\u03b2-lactamase inhibition by bisthiazolidines reveals multiple binding modes","volume":"113","author":"Hinchliffe","year":"2016","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026082504494312100_dkag291-B16","doi-asserted-by":"publisher","first-page":"10634","DOI":"10.1021\/bi0342822","article-title":"Crystal structure of extended-spectrum \u03b2-lactamase Toho-1: insights into the molecular mechanism for catalytic reaction and substrate specificity expansion","volume":"42","author":"Ibuka","year":"2003","journal-title":"Biochemistry"},{"key":"2026082504494312100_dkag291-B17","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00775-24","article-title":"Relative inhibitory activities of newly developed diazabicyclooctanes, boronic acid derivatives, and penicillin-based sulfone \u03b2-lactamase inhibitors against broad-spectrum AmpC \u03b2-lactamases","volume":"68","author":"Le Terrier","year":"2024","journal-title":"Antimicrob Agents Chemother"},{"key":"2026082504494312100_dkag291-B18","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1005595","article-title":"Unicycler: resolving bacterial genome assemblies from short and long sequencing reads","volume":"13","author":"Wick","year":"2017","journal-title":"PLoS Comput Biol"},{"key":"2026082504494312100_dkag291-B19","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02529-16","article-title":"WCK 5107 (Zidebactam) and WCK 5153 are novel inhibitors of PBP2 showing potent \u201c\u03b2-lactam enhancer\u201d activity against Pseudomonas aeruginosa, including multidrug-resistant metallo-\u03b2-lactamase-producing high-risk clones","volume":"61","author":"Moya","year":"2017","journal-title":"Antimicrob Agents Chemother"}],"container-title":["Journal of Antimicrobial Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/81\/9\/dkag291\/70775591\/dkag291.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/81\/9\/dkag291\/70775591\/dkag291.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T08:49:47Z","timestamp":1787647787000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jac\/article\/doi\/10.1093\/jac\/dkag291\/8769928"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,4]]},"references-count":19,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,8,4]]}},"URL":"https:\/\/doi.org\/10.1093\/jac\/dkag291","relation":{},"ISSN":["0305-7453","1460-2091"],"issn-type":[{"value":"0305-7453","type":"print"},{"value":"1460-2091","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,9]]},"published":{"date-parts":[[2026,8,4]]},"article-number":"dkag291"}}