{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T03:22:13Z","timestamp":1790565733638,"version":"4.1.0"},"reference-count":46,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,5,20]],"date-time":"2020-05-20T00:00:00Z","timestamp":1589932800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"BioNano Health-Guard Research Center  Ministry of Science, ICT &amp; Future Planning (MSIP) of Korea as a Global Frontier Project","award":["H-GUARD_2014M3A6B2060509"],"award-info":[{"award-number":["H-GUARD_2014M3A6B2060509"]}]},{"DOI":"10.13039\/501100003668","name":"Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry and Fisheries","doi-asserted-by":"publisher","award":["IPET"],"award-info":[{"award-number":["IPET"]}],"id":[{"id":"10.13039\/501100003668","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Agriculture, Food and Rural Affairs(MAFRA)","award":["918003-4"],"award-info":[{"award-number":["918003-4"]}]},{"name":"National Institute of Health, Korea","award":["2019ER540300R514931"],"award-info":[{"award-number":["2019ER540300R514931"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>This study investigates GT-1 (also known as LCB10-0200), a novel-siderophore cephalosporin, inhibited multidrug-resistant (MDR) Gram-negative pathogen, via a Trojan horse strategy exploiting iron-uptake systems. We investigated GT-1 activity and the role of siderophore uptake systems, and the combination of GT-1 and a non-\u03b2-lactam \u03b2-lactamase inhibitor (BLI) of diazabicyclooctane, GT-055, (also referred to as LCB18-055) against molecularly characterised resistant Escherichia coli, Klebsiella pneumoniae and Acinetobacter spp. isolates. GT-1 and GT-1\/GT-055 were tested in vitro against comparators among three different characterised panel strain sets. Bacterial resistome and siderophore uptake systems were characterised to elucidate the genetic basis for GT-1 minimum inhibitory concentrations (MICs). GT-1 exhibited in vitro activity (\u22642 \u03bcg\/mL MICs) against many MDR isolates, including extended-spectrum \u03b2-lactamase (ESBL)- and carbapenemase-producing E. coli and K. pneumoniae and oxacillinase (OXA)-producing Acinetobacter spp. GT-1 also inhibited strains with mutated siderophore transporters and porins. Although BLI GT-055 exhibited intrinsic activity (MIC 2\u20138 \u03bcg\/mL) against most E. coli and K. pneumoniae isolates, GT-055 enhanced the activity of GT-1 against many GT-1\u2013resistant strains. Compared with CAZ-AVI, GT-1\/GT-055 exhibited lower MICs against E. coli and K. pneumoniae isolates. GT-1 demonstrated potent in vitro activity against clinical panel strains of E. coli, K. pneumoniae and Acinetobacter spp. GT-055 enhanced the in vitro activity of GT-1 against many GT-1\u2013resistant strains.<\/jats:p>","DOI":"10.3390\/antibiotics9050267","type":"journal-article","created":{"date-parts":[[2020,5,20]],"date-time":"2020-05-20T10:37:38Z","timestamp":1589971058000},"page":"267","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["In Vitro Activity of a Novel Siderophore-Cephalosporin, GT-1 and Serine-Type \u03b2-Lactamase Inhibitor, GT-055, against Escherichia coli, Klebsiella pneumoniae and Acinetobacter spp. Panel Strains"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6123-5426","authenticated-orcid":false,"given":"Le Phuong","family":"Nguyen","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Research Institute of Bacterial Resistance, College of Medicine, Yonsei University, Seoul 03722, Korea"},{"name":"Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8348-8990","authenticated-orcid":false,"given":"Naina Adren","family":"Pinto","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Research Institute of Bacterial Resistance, College of Medicine, Yonsei University, Seoul 03722, Korea"},{"name":"Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7393-745X","authenticated-orcid":false,"given":"Thao Nguyen","family":"Vu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Research Institute of Bacterial Resistance, College of Medicine, Yonsei University, Seoul 03722, Korea"},{"name":"Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0179-9999","authenticated-orcid":false,"given":"Hyunsook","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Research Institute of Bacterial Resistance, College of Medicine, Yonsei University, Seoul 03722, Korea"},{"name":"Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5787-9605","authenticated-orcid":false,"given":"Young Lag","family":"Cho","sequence":"additional","affiliation":[{"name":"Legochem Biosciences, Daejeon 34302, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5909-5807","authenticated-orcid":false,"given":"Jung-Hyun","family":"Byun","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Gyeongsang National University College of Medicine, Gyeongsang National University Hospital, Jinju 52727, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6576-7574","authenticated-orcid":false,"given":"Roshan","family":"D\u2019Souza","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Research Institute of Bacterial Resistance, College of Medicine, Yonsei University, Seoul 03722, Korea"},{"name":"J. Craig Venter Institute, Rockville, MD 20850, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1225-8477","authenticated-orcid":false,"given":"Dongeun","family":"Yong","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Research Institute of Bacterial Resistance, College of Medicine, Yonsei University, Seoul 03722, Korea"},{"name":"Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/S1473-3099(17)30753-3","article-title":"Discovery, research, and development of new antibiotics: The WHO priority list of antibiotic-resistant bacteria and tuberculosis","volume":"18","author":"Tacconelli","year":"2018","journal-title":"Lancet Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Nguyen, L.P., Pinto, N.A., Vu, T.N., Mai, H., Pham, A.H., Lee, H., Cho, Y.L., Byun, J.-H., D\u2019Souza, R., and Yong, D. (2019). Resistome profiles, plasmid typing, and whole-genome phylogenetic tree analyses of blaNDM-9 and mcr-1 co-harboring Escherichia coli ST617 from a patient without a history of farm exposure in Korea. Pathogens, 8.","DOI":"10.3390\/pathogens8040212"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e00317-17","DOI":"10.1128\/AAC.00317-17","article-title":"Emergence of the plasmid-mediated mcr-1 gene in clinical KPC-2-producing Klebsiella pneumoniae sequence type 392 in Brazil","volume":"61","author":"Aires","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1038\/nrmicro2333","article-title":"How antibiotics kill bacteria: From targets to networks","volume":"8","author":"Kohanski","year":"2010","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"16044","DOI":"10.1038\/nmicrobiol.2016.44","article-title":"Antibiotics as a selective driver for conjugation dynamics","volume":"1","author":"Lopatkin","year":"2016","journal-title":"Nat. Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1128\/AAC.01388-10","article-title":"Efflux-mediated antibiotic resistance in Acinetobacter spp.","volume":"55","author":"Coyne","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1016\/j.ijantimicag.2017.06.001","article-title":"Antimicrobial activities of LCB10-0200, a novel siderophore cephalosporin, against the clinical isolates of Pseudomonas aeruginosa and other pathogens","volume":"50","author":"Oh","year":"2017","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1039\/C8MD00342D","article-title":"\u03b2-lactam\/\u03b2-lactamase inhibitor combinations: An update","volume":"9","author":"Tehrani","year":"2018","journal-title":"MedChemComm"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e01443-17","DOI":"10.1128\/AAC.01443-17","article-title":"Vaborbactam: Spectrum of beta-lactamase inhibition and impact of resistance mechanisms on activity in Enterobacteriaceae","volume":"61","author":"Lomovskaya","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"5704","DOI":"10.1128\/AAC.03057-14","article-title":"Avibactam and class C \u03b2-lactamases: Mechanism of inhibition, conservation of the binding pocket, and implications for resistance","volume":"58","author":"Lahiri","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_11","unstructured":"Lee, J., Shin, S., Biek, D., and Cho, Y. (2019). Penicillin binding protein (PBP) activity of beta-lactamase inhibitor GT-055. Posters of the Twenty Ninth European Congress of Clinical Microbiology & Infectious Diseases, Amsterdam, Netherlands, European Society of Clinical Microbiology. Poster 1187."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3382","DOI":"10.1128\/IAI.00540-13","article-title":"Functional features of TonB energy transduction systems of Acinetobacter baumannii","volume":"81","author":"Zimbler","year":"2013","journal-title":"Infect. Immun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1016\/j.tim.2018.02.006","article-title":"Towards understanding MCR-like colistin resistance","volume":"26","author":"Sun","year":"2018","journal-title":"Trends Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/S0168-6445(03)00055-X","article-title":"Bacterial iron homeostasis","volume":"27","author":"Andrews","year":"2003","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"344","DOI":"10.3389\/fcimb.2018.00344","article-title":"Editorial: Role of iron in bacterial pathogenesis","volume":"8","author":"Zughaier","year":"2018","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1007\/s10534-009-9219-2","article-title":"Siderophores as drug delivery agents: Application of the \u201cTrojan Horse\u201d strategy","volume":"22","author":"Heinisch","year":"2009","journal-title":"Biometals"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Eijkelkamp, B.A., Hassan, K.A., Paulsen, I.T., and Brown, M.H. (2011). Investigation of the human pathogen Acinetobacter baumannii under iron limiting conditions. BMC Genom., 12.","DOI":"10.1186\/1471-2164-12-126"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3472","DOI":"10.1016\/j.jmb.2019.04.002","article-title":"\u03b2-lactamases and \u03b2-lactamase inhibitors in the 21st century","volume":"431","author":"Tooke","year":"2019","journal-title":"J. Mol. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1093\/jac\/dkz026","article-title":"Ceftazidime\/avibactam resistance associated with L169P mutation in the omega loop of KPC-2","volume":"74","author":"Hemarajata","year":"2019","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2466","DOI":"10.1093\/jac\/dkz201","article-title":"Identification of L169P mutation in the omega loop of KPC-3 after a short course of ceftazidime\/avibactam","volume":"74","author":"Venditti","year":"2019","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e2896","DOI":"10.7717\/peerj.2896","article-title":"Panel strain of Klebsiella pneumoniae for beta-lactam antibiotic evaluation: Their phenotypic and genotypic characterization","volume":"5","author":"Dsouza","year":"2017","journal-title":"PeerJ"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"559","DOI":"10.3389\/fmicb.2019.00559","article-title":"Phenotypic and genotypic characterization of Acinetobacter spp. panel strains: A cornerstone to facilitate antimicrobial development","volume":"10","author":"Pinto","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1111\/j.1469-0691.2011.03570.x","article-title":"Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: An international expert proposal for interim standard definitions for acquired resistance","volume":"18","author":"Magiorakos","year":"2012","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_24","unstructured":"CLSI (2015). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically M7-A10, Clinical and Laboratory Standards Institute."},{"key":"ref_25","unstructured":"CLSI (2018). Performance Standards for Antimicrobial Susceptibility Testing Twenty-eighth Informational Supplement M100-S28, Clinical and Laboratory Standards Institute."},{"key":"ref_26","unstructured":"Oh, S., Kwak, J., Lee, J., Han, H., Biek, D., Oh, K., and Cho, Y. (2018). Serum and iron effects on the in vitro activity of siderophore cephalosporin GT-1. Posters of American Society for Microbiology (ASM) Microbe 2018, American Society for Microbiology."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1089\/cmb.2012.0021","article-title":"SPAdes: A new genome assembly algorithm and its applications to single-cell sequencing","volume":"19","author":"Bankevich","year":"2012","journal-title":"J. Comput. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Aziz, R.K., Bartels, D., Best, A.A., DeJongh, M., Disz, T., Edwards, R.A., Formsma, K., Gerdes, S., Glass, E.M., and Kubal, M. (2008). The RAST Server: Rapid annotations using subsystems technology. BMC Genom., 9.","DOI":"10.1186\/1471-2164-9-75"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2640","DOI":"10.1093\/jac\/dks261","article-title":"Identification of acquired antimicrobial resistance genes","volume":"67","author":"Zankari","year":"2012","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3895","DOI":"10.1128\/AAC.02412-14","article-title":"In silico detection and typing of plasmids using PlasmidFinder and plasmid multilocus sequence typing","volume":"58","author":"Carattoli","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1002\/0471250953.bi1107s32","article-title":"Aligning short sequencing reads with Bowtie","volume":"32","author":"Langmead","year":"2010","journal-title":"Curr. Protoc. Bioinform."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.tim.2005.06.005","article-title":"TonB-dependent trans-envelope signalling: The exception or the rule?","volume":"13","author":"Koebnik","year":"2005","journal-title":"Trends Microbiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/S0014-5793(02)03185-X","article-title":"Iron transport and signaling in Escherichia coli","volume":"529","author":"Braun","year":"2002","journal-title":"FEBS Lett."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1099\/13500872-141-7-1647","article-title":"Escherichia coli periplasmic protein FepB binds ferrienterobactin","volume":"141","author":"Stephens","year":"1995","journal-title":"Microbiology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1128\/jb.166.3.930-936.1986","article-title":"Escherichia coli K-12 envelope proteins specifically required for ferrienterobactin uptake","volume":"166","author":"Pierce","year":"1986","journal-title":"J. Bacteriol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1111\/j.1365-2958.1991.tb00788.x","article-title":"Nucleotide sequence and genetic organization of the ferric enterobactin transport system: Homology to other periplasmic binding protein-dependent systems in Escherichia coli","volume":"5","author":"Shea","year":"1991","journal-title":"Mol. Microbiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2871","DOI":"10.1046\/j.1432-1327.2000.01296.x","article-title":"Proteomic analysis of the Escherichia coli outer membrane","volume":"267","author":"Molloy","year":"2000","journal-title":"Eur. J. Biochem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1128\/IAI.01222-10","article-title":"Redundancy and specificity of Escherichia coli iron acquisition systems during urinary tract infection","volume":"79","author":"Garcia","year":"2011","journal-title":"Infect. Immun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3657","DOI":"10.1099\/mic.0.27371-0","article-title":"The siderophore-mediated iron acquisition systems of Acinetobacter baumannii ATCC 19606 and Vibrio anguillarum 775 are structurally and functionally related","volume":"150","author":"Dorsey","year":"2004","journal-title":"Microbiology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2587","DOI":"10.1099\/mic.0.27141-0","article-title":"Identification and transcriptional organization of a gene cluster involved in biosynthesis and transport of acinetobactin, a siderophore produced by Acinetobacter baumannii ATCC 19606T","volume":"150","author":"Mihara","year":"2004","journal-title":"Microbiology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1128\/IAI.02925-14","article-title":"Role of the carboxy terminus of SecA in iron acquisition, protein translocation, and virulence of the bacterial pathogen Acinetobacter baumannii","volume":"83","author":"Fiester","year":"2015","journal-title":"Infect. Immun."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"7670","DOI":"10.1128\/jb.174.23.7670-7679.1992","article-title":"Characterization of a high-affinity iron transport system in Acinetobacter baumannii","volume":"174","author":"Echenique","year":"1992","journal-title":"J. Bacteriol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e02531-16","DOI":"10.1128\/AAC.02531-16","article-title":"Structure and function of the PiuA and PirA siderophore-drug receptors from Pseudomonas aeruginosa and Acinetobacter baumannii","volume":"61","author":"Luscher","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3677","DOI":"10.1073\/pnas.0737682100","article-title":"Salmochelins, siderophores of Salmonella enterica and uropathogenic Escherichia coli strains, are recognized by the outer membrane receptor IroN","volume":"100","author":"Hantke","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1099\/mic.0.2007\/011981-0","article-title":"The ferric yersiniabactin uptake receptor FyuA is required for efficient biofilm formation by urinary tract infectious Escherichia coli in human urine","volume":"154","author":"Hancock","year":"2008","journal-title":"Microbiology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1896","DOI":"10.1002\/cbic.201500147","article-title":"Discovery and characterization of new hydroxamate siderophores, baumannoferrin A and B, produced by Acinetobacter baumannii","volume":"16","author":"Penwell","year":"2015","journal-title":"ChemBioChem"}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/9\/5\/267\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:30:51Z","timestamp":1760175051000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/9\/5\/267"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,20]]},"references-count":46,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2020,5]]}},"alternative-id":["antibiotics9050267"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics9050267","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,20]]}}}