{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T21:22:04Z","timestamp":1781731324911,"version":"3.54.5"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2022,6,17]],"date-time":"2022-06-17T00:00:00Z","timestamp":1655424000000},"content-version":"vor","delay-in-days":45,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002301","name":"Estonian Research Council","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002301","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Swedish Research council"},{"DOI":"10.13039\/501100001348","name":"Agency for Science, Technology and Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001348","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,5,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Listeriosis is a food-borne disease caused by the Gram-positive Bacillota (Firmicute) bacterium Listeria monocytogenes. Clinical L. monocytogenes isolates are often resistant to clinically used lincosamide clindamycin, thus excluding clindamycin as a viable treatment option.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>We have established newly developed lincosamide iboxamycin as a potential novel antilisterial agent.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We determined MICs of the lincosamides lincomycin, clindamycin and iboxamycin for L. monocytogenes, Enterococcus faecalis and Bacillus subtilis strains expressing synergetic antibiotic resistance determinants: ABCF ATPases that directly displace antibiotics from the ribosome and Cfr, a 23S rRNA methyltransferase that compromises antibiotic binding. For L. monocytogenes strains, either expressing VgaL\/Lmo0919 or lacking the resistance factor, we performed time-kill kinetics and post-antibiotic effect assays.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We show that the synthetic lincosamide iboxamycin is highly active against L. monocytogenes and can overcome the intrinsic lincosamide resistance mediated by VgaL\/Lmo0919 ABCF ATPase. While iboxamycin is not bactericidal against L. monocytogenes, it displays a pronounced post-antibiotic effect, which is a valuable pharmacokinetic feature. We demonstrate that VmlR ABCF of B. subtilis grants significant (33-fold increase in MIC) protection from iboxamycin, while LsaA ABCF of E. faecalis grants an 8-fold protective effect. Furthermore, the VmlR-mediated iboxamycin resistance is cooperative with that mediated by the Cfr, resulting in up to a 512-fold increase in MIC.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>While iboxamycin is a promising new antilisterial agent, our findings suggest that emergence and spread of ABCF ARE variants capable of defeating next-generation lincosamides in the clinic is possible and should be closely monitored.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jacamr\/dlac061","type":"journal-article","created":{"date-parts":[[2022,6,17]],"date-time":"2022-06-17T08:11:10Z","timestamp":1655453470000},"source":"Crossref","is-referenced-by-count":10,"title":["Synthetic oxepanoprolinamide iboxamycin is active against <i>Listeria monocytogenes<\/i> despite the intrinsic resistance mediated by VgaL\/Lmo0919 ABCF ATPase"],"prefix":"10.1093","volume":"4","author":[{"given":"Tetiana","family":"Brodiazhenko","sequence":"first","affiliation":[{"name":"University of Tartu, Institute of Technology , 50411 Tartu , Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn Jane","family":"Turnbull","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology, Rigshospitalet , 2200 Copenhagen , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelvin J Y","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Chemical Biology, Harvard University , Cambridge, MA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiraku","family":"Takada","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Lund , 221 84 Lund , Sweden"},{"name":"Faculty of Life Sciences, Kyoto Sangyo University , Kamigamo, Motoyama, Kita-ku, Kyoto 603-8555 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben I C","family":"Tresco","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Chemical Biology, Harvard University , Cambridge, MA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanel","family":"Tenson","sequence":"additional","affiliation":[{"name":"University of Tartu, Institute of Technology , 50411 Tartu , Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew G","family":"Myers","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Chemical Biology, Harvard University , Cambridge, MA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2389-5057","authenticated-orcid":false,"given":"Vasili","family":"Hauryliuk","sequence":"additional","affiliation":[{"name":"University of Tartu, Institute of Technology , 50411 Tartu , Estonia"},{"name":"Department of Experimental Medicine, University of Lund , 221 84 Lund , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,6,17]]},"reference":[{"key":"2022072608215752500_dlac061-B1","doi-asserted-by":"crossref","first-page":"a027037","DOI":"10.1101\/cshperspect.a027037","article-title":"Lincosamides, streptogramins, phenicols, and pleuromutilins: mode of action and mechanisms of resistance","volume":"6","author":"Schwarz","year":"2016","journal-title":"Cold Spring Harb Perspect Med"},{"key":"2022072608215752500_dlac061-B2","doi-asserted-by":"crossref","first-page":"10284","DOI":"10.1093\/nar\/gkx658","article-title":"Structural insights of lincosamides targeting the ribosome of Staphylococcus aureus","volume":"45","author":"Matzov","year":"2017","journal-title":"Nucleic Acids Res"},{"key":"2022072608215752500_dlac061-B3","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.cell.2005.02.005","article-title":"Structures of MLSBK antibiotics bound to mutated large ribosomal subunits provide a structural explanation for resistance","volume":"121","author":"Tu","year":"2005","journal-title":"Cell"},{"key":"2022072608215752500_dlac061-B4","doi-asserted-by":"crossref","first-page":"17152","DOI":"10.1073\/pnas.1007988107","article-title":"Structures of the Escherichia coli ribosome with antibiotics bound near the peptidyl transferase center explain spectra of drug action","volume":"107","author":"Dunkle","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2022072608215752500_dlac061-B5","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1038\/35101544","article-title":"Structural basis for the interaction of antibiotics with the peptidyl transferase centre in eubacteria","volume":"413","author":"Schlunzen","year":"2001","journal-title":"Nature"},{"key":"2022072608215752500_dlac061-B6","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.bcp.2016.12.001","article-title":"Lincosamides: Chemical structure, biosynthesis, mechanism of action, resistance, and applications","volume":"133","author":"Sp\u00ed\u017eek","year":"2017","journal-title":"Biochem Pharmacol"},{"key":"2022072608215752500_dlac061-B7","first-page":"1056","article-title":"Lincomycin: a new antibiotic active against staphylococci and other Gram-positive cocci: clinical and laboratory studies","volume":"91","author":"Macleod","year":"1964","journal-title":"Can Med Assoc J"},{"key":"2022072608215752500_dlac061-B8","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1021\/jm00298a007","article-title":"XI. Synthesis and structure of clindamycin. A potent antibacterial agent","volume":"13","author":"Birkenmeyer","year":"1970","journal-title":"J Med Chem"},{"issue":"Suppl A","key":"2022072608215752500_dlac061-B9","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1093\/jac\/7.suppl_A.11","article-title":"Past and current use of clindamycin and lincomycin","volume":"7","author":"Phillips","year":"1981","journal-title":"J Antimicrob Chemother"},{"key":"2022072608215752500_dlac061-B10","first-page":"22","article-title":"Current indications for the use of clindamycin: a critical review","volume":"9","author":"Smieja","year":"1998","journal-title":"Can J Infect Dis"},{"key":"2022072608215752500_dlac061-B11","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1128\/AAC.21.6.902","article-title":"In vitro activity of U-57930E, a new clindamycin analog, against aerobic Gram-positive bacteria","volume":"21","author":"Ahonkhai","year":"1982","journal-title":"Antimicrob Agents Chemother"},{"key":"2022072608215752500_dlac061-B12","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1021\/jm00368a020","article-title":"Synthesis and antimicrobial activity of clindamycin analogues: pirlimycin, a potent antibacterial agent","volume":"27","author":"Birkenmeyer","year":"1984","journal-title":"J Med Chem"},{"key":"2022072608215752500_dlac061-B13","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1038\/s41429-020-00375-1","article-title":"Characterization of compound A, a novel lincomycin derivative active against methicillin-resistant Staphylococcus aureus","volume":"74","author":"Hirai","year":"2021","journal-title":"J Antibiot (Tokyo)"},{"key":"2022072608215752500_dlac061-B14","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1038\/s41586-021-04045-6","article-title":"A synthetic antibiotic class overcoming bacterial multidrug resistance","volume":"599","author":"Mitcheltree","year":"2021","journal-title":"Nature"},{"key":"2022072608215752500_dlac061-B15","doi-asserted-by":"crossref","first-page":"2500","DOI":"10.1128\/AAC.00131-06","article-title":"The Cfr rRNA methyltransferase confers resistance to phenicols, lincosamides, oxazolidinones, pleuromutilins, and streptogramin A antibiotics","volume":"50","author":"Long","year":"2006","journal-title":"Antimicrob Agents Chemother"},{"key":"2022072608215752500_dlac061-B16","doi-asserted-by":"crossref","first-page":"2530","DOI":"10.1128\/AAC.44.9.2530-2533.2000","article-title":"Identification of a plasmid-borne chloramphenicol-florfenicol resistance gene in Staphylococcus sciuri","volume":"44","author":"Schwarz","year":"2000","journal-title":"Antimicrob Agents Chemother"},{"key":"2022072608215752500_dlac061-B17","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/0378-1119(85)90208-2","article-title":"N-Methyl transferase of Streptomyces erythraeus that confers resistance to the macrolide-lincosamide-streptogramin B antibiotics: amino acid sequence and its homology to cognate R-factor enzymes from pathogenic bacilli and cocci","volume":"38","author":"Uchiyama","year":"1985","journal-title":"Gene"},{"key":"2022072608215752500_dlac061-B18","doi-asserted-by":"crossref","first-page":"193","DOI":"10.2174\/1568005043340777","article-title":"Macrolide resistance based on the Erm-mediated rRNA methylation","volume":"4","author":"Maravic","year":"2004","journal-title":"Curr Drug Targets Infect Disord"},{"key":"2022072608215752500_dlac061-B19","doi-asserted-by":"crossref","first-page":"1845","DOI":"10.1128\/AAC.46.6.1845-1850.2002","article-title":"An Enterococcus faecalis ABC homologue (Lsa) is required for the resistance of this species to clindamycin and quinupristin-dalfopristin","volume":"46","author":"Singh","year":"2002","journal-title":"Antimicrob Agents Chemother"},{"key":"2022072608215752500_dlac061-B20","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1038\/s41579-020-0386-z","article-title":"Target protection as a key antibiotic resistance mechanism","volume":"18","author":"Wilson","year":"2020","journal-title":"Nat Rev Microbiol"},{"key":"2022072608215752500_dlac061-B21","doi-asserted-by":"crossref","first-page":"3568","DOI":"10.1016\/j.jmb.2018.12.013","article-title":"ABCF ATPases involved in protein synthesis, ribosome assembly and antibiotic resistance: structural and functional diversification across the tree of life","volume":"431","author":"Murina","year":"2019","journal-title":"J Mol Biol"},{"key":"2022072608215752500_dlac061-B22","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1002\/pro.3589","article-title":"Ribosome protection by ABC-F proteins-molecular mechanism and potential drug design","volume":"28","author":"Ero","year":"2019","journal-title":"Protein Sci"},{"key":"2022072608215752500_dlac061-B23","doi-asserted-by":"crossref","first-page":"3577","DOI":"10.1038\/s41467-021-23753-1","article-title":"Structural basis of ABCF-mediated resistance to pleuromutilin, lincosamide, and streptogramin A antibiotics in Gram-positive pathogens","volume":"12","author":"Crowe-McAuliffe","year":"2021","journal-title":"Nat Commun"},{"key":"2022072608215752500_dlac061-B24","doi-asserted-by":"crossref","first-page":"3753","DOI":"10.1093\/nar\/gky050","article-title":"Antibiotic resistance ABCF proteins reset the peptidyl transferase centre of the ribosome to counter translational arrest","volume":"46","author":"Murina","year":"2018","journal-title":"Nucleic Acids Res"},{"key":"2022072608215752500_dlac061-B25","doi-asserted-by":"crossref","first-page":"e01975","DOI":"10.1128\/mBio.01975-15","article-title":"ABC-F proteins mediate antibiotic resistance through ribosomal protection","volume":"7","author":"Sharkey","year":"2016","journal-title":"mBio"},{"key":"2022072608215752500_dlac061-B26","doi-asserted-by":"crossref","first-page":"5157","DOI":"10.1073\/pnas.1803313115","article-title":"Ribosome protection by antibiotic resistance ATP-binding cassette protein","volume":"115","author":"Su","year":"2018","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2022072608215752500_dlac061-B27","doi-asserted-by":"crossref","first-page":"8978","DOI":"10.1073\/pnas.1808535115","article-title":"Structural basis for antibiotic resistance mediated by the Bacillus subtilis ABCF ATPase VmlR","volume":"115","author":"Crowe-McAuliffe","year":"2018","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2022072608215752500_dlac061-B28","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1038\/nrmicro.2017.126","article-title":"Listeria monocytogenes: towards a complete picture of its physiology and pathogenesis","volume":"16","author":"Radoshevich","year":"2018","journal-title":"Nat Rev Microbiol"},{"key":"2022072608215752500_dlac061-B29","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1056\/NEJM198301273080407","article-title":"Epidemic listeriosis\u2013evidence for transmission by food","volume":"308","author":"Schlech","year":"1983","journal-title":"N Engl J Med"},{"key":"2022072608215752500_dlac061-B30","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1056\/NEJM199603213341206","article-title":"Intracellular pathogenesis of listeriosis","volume":"334","author":"Southwick","year":"1996","journal-title":"N Engl J Med"},{"key":"2022072608215752500_dlac061-B31","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1016\/S1473-3099(14)70870-9","article-title":"The global burden of listeriosis: a systematic review and meta-analysis","volume":"14","author":"de Noordhout","year":"2014","journal-title":"Lancet Infect Dis"},{"key":"2022072608215752500_dlac061-B32","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1097\/00005792-199809000-00002","article-title":"Central nervous system infection with Listeria monocytogenes. 33 years\u2019 experience at a general hospital and review of 776 episodes from the literature","volume":"77","author":"Mylonakis","year":"1998","journal-title":"Medicine (Baltimore)"},{"key":"2022072608215752500_dlac061-B33","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1345\/aph.19315","article-title":"Treatment of listeriosis","volume":"34","author":"Temple","year":"2000","journal-title":"Ann Pharmacother"},{"key":"2022072608215752500_dlac061-B34","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1089\/fpd.2019.2723","article-title":"Antimicrobial susceptibility and multilocus sequence typing of Listeria monocytogenes isolated over 11 years from food, humans, and the environment in Italy","volume":"17","author":"Caruso","year":"2020","journal-title":"Foodborne Pathog Dis"},{"key":"2022072608215752500_dlac061-B35","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.3390\/antibiotics10101206","article-title":"Antimicrobial resistance of Listeria monocytogenes strains isolated from humans, animals, and food products in Russia in 1950-1980, 2000-2005, and 2018-2021","volume":"10","author":"Andriyanov","year":"2021","journal-title":"Antibiotics (Basel)"},{"key":"2022072608215752500_dlac061-B36","doi-asserted-by":"crossref","first-page":"108912","DOI":"10.1016\/j.ijfoodmicro.2020.108912","article-title":"Distribution, virulence, genotypic characteristics and antibiotic resistance of Listeria monocytogenes isolated over one-year monitoring from two pig slaughterhouses and processing plants and their fresh hams","volume":"336","author":"Rugna","year":"2021","journal-title":"Int J Food Microbiol"},{"key":"2022072608215752500_dlac061-B37","doi-asserted-by":"crossref","first-page":"54","DOI":"10.4315\/JFP-21-172","article-title":"Diversity and antibiotic resistance profiles of Listeria monocytogenes serogroups in different food products from the Transylvania Region of Central Romania","volume":"85","author":"Tirziu","year":"2022","journal-title":"J Food Prot"},{"key":"2022072608215752500_dlac061-B38","doi-asserted-by":"crossref","first-page":"aad9822","DOI":"10.1126\/science.aad9822","article-title":"Term-seq reveals abundant ribo-regulation of antibiotics resistance in bacteria","volume":"352","author":"Dar","year":"2016","journal-title":"Science"},{"key":"2022072608215752500_dlac061-B39","doi-asserted-by":"crossref","first-page":"5946","DOI":"10.1128\/JB.187.17.5946-5954.2005","article-title":"Transcriptional termination control of a novel ABC transporter gene involved in antibiotic resistance in Bacillus subtilis","volume":"187","author":"Ohki","year":"2005","journal-title":"J Bacteriol"},{"key":"2022072608215752500_dlac061-B40","doi-asserted-by":"crossref","first-page":"11019","DOI":"10.1021\/jacs.1c03529","article-title":"Practical Gram-scale synthesis of iboxamycin, a potent antibiotic candidate","volume":"143","author":"Mason","year":"2021","journal-title":"J Am Chem Soc"},{"key":"2022072608215752500_dlac061-B41","doi-asserted-by":"crossref","first-page":"e0145655","DOI":"10.1371\/journal.pone.0145655","article-title":"Biochemical and computational analysis of the substrate specificities of Cfr and RlmN methyltransferases","volume":"10","author":"Ntokou","year":"2015","journal-title":"PLoS One"},{"key":"2022072608215752500_dlac061-B42","volume-title":"Performance Standards for Antimicrobial Susceptibility Testing\u2014Twenty-Sixth Edition: M100","author":"CLSI","year":"2016"},{"key":"2022072608215752500_dlac061-B43","doi-asserted-by":"crossref","first-page":"13673","DOI":"10.1073\/pnas.1717168115","article-title":"Kinetics of drug-ribosome interactions defines the cidality of macrolide antibiotics","volume":"114","author":"Svetlov","year":"2017","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2022072608215752500_dlac061-B44","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1126\/science.1063447","article-title":"Comparative genomics of Listeria species","volume":"294","author":"Glaser","year":"2001","journal-title":"Science"},{"key":"2022072608215752500_dlac061-B45","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1128\/jb.96.2.352-357.1968","article-title":"Listeria monocytogenes L forms. I. Induction maintenance, and biological characteristics","volume":"96","author":"Edman","year":"1968","journal-title":"J Bacteriol"},{"key":"2022072608215752500_dlac061-B46","doi-asserted-by":"crossref","first-page":"e00969-14","DOI":"10.1128\/mBio.00969-14","article-title":"Comparison of widely used Listeria monocytogenes strains EGD, 10403S, and EGD-e highlights genomic variations underlying differences in pathogenicity","volume":"5","author":"B\u00e9cavin","year":"2014","journal-title":"mBio"},{"key":"2022072608215752500_dlac061-B47","doi-asserted-by":"crossref","first-page":"4881","DOI":"10.1128\/JB.184.17.4881-4890.2002","article-title":"Genome-wide analysis of the stationary-phase sigma factor (sigma-H) regulon of Bacillus subtilis","volume":"184","author":"Britton","year":"2002","journal-title":"J Bacteriol"},{"key":"2022072608215752500_dlac061-B48","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1038\/nchembio.1796","article-title":"Translating slow-binding inhibition kinetics into cellular and in vivo effects","volume":"11","author":"Walkup","year":"2015","journal-title":"Nat Chem Biol"},{"key":"2022072608215752500_dlac061-B49","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1093\/clinids\/3.1.28","article-title":"Postantibiotic suppression of bacterial growth","volume":"3","author":"Bundtzen","year":"1981","journal-title":"Rev Infect Dis"},{"key":"2022072608215752500_dlac061-B50","doi-asserted-by":"crossref","first-page":"2128","DOI":"10.1093\/nar\/gkac058","article-title":"Sal-type ABC-F proteins: intrinsic and common mediators of pleuromutilin resistance by target protection in staphylococci","volume":"50","author":"Mohamad","year":"2022","journal-title":"Nucleic Acids Res"},{"key":"2022072608215752500_dlac061-B51","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1021\/acsinfecdis.7b00251","article-title":"Antibiotic resistance ABC-F proteins: bringing target protection into the limelight","volume":"4","author":"Sharkey","year":"2018","journal-title":"ACS Infect Dis"},{"key":"2022072608215752500_dlac061-B52","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/0002-9343(90)90099-Y","article-title":"Once-daily dosing regimen for aminoglycoside plus \u03b2-lactam combination therapy of serious bacterial infections: comparative trial with netilmicin plus ceftriaxone","volume":"89","author":"ter Braak","year":"1990","journal-title":"Am J Med"},{"key":"2022072608215752500_dlac061-B53","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1128\/AAC.35.3.399","article-title":"Once-daily aminoglycoside therapy","volume":"35","author":"Gilbert","year":"1991","journal-title":"Antimicrob Agents Chemother"}],"container-title":["JAC-Antimicrobial Resistance"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jacamr\/article-pdf\/4\/3\/dlac061\/45065046\/dlac061.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jacamr\/article-pdf\/4\/3\/dlac061\/45065046\/dlac061.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,26]],"date-time":"2022-07-26T08:23:00Z","timestamp":1658823780000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jacamr\/article\/doi\/10.1093\/jacamr\/dlac061\/6609611"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,3]]},"references-count":53,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2022,5,3]]}},"URL":"https:\/\/doi.org\/10.1093\/jacamr\/dlac061","relation":{},"ISSN":["2632-1823"],"issn-type":[{"value":"2632-1823","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,6,1]]},"published":{"date-parts":[[2022,5,3]]},"article-number":"dlac061"}}