{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:36:29Z","timestamp":1790958989022,"version":"4.1.0"},"reference-count":51,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,2,11]],"date-time":"2022-02-11T00:00:00Z","timestamp":1644537600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004271","name":"Sapienza University of Rome","doi-asserted-by":"publisher","award":["RM11916B6A28725C"],"award-info":[{"award-number":["RM11916B6A28725C"]}],"id":[{"id":"10.13039\/501100004271","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004271","name":"Sapienza University of Rome","doi-asserted-by":"publisher","award":["RM11916B6A8B5F8D"],"award-info":[{"award-number":["RM11916B6A8B5F8D"]}],"id":[{"id":"10.13039\/501100004271","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Pasteur-Italia Fondazione Cenci Bolognetti","award":["Anna Tramontano Grant 2018"],"award-info":[{"award-number":["Anna Tramontano Grant 2018"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Multidrug-resistant microbial infections and the scarce availability of new antibiotics capable of eradicating them are posing a serious problem to global health security. Among the microorganisms that easily acquire resistance to antibiotics and that are the etiological cause of severe infections, there is Acinetobacter baumannii. Carbapenems are the principal agents used to treat A. baumannii infections. However, when strains develop resistance to this class of antibiotics, colistin is considered one of the last-resort drugs. However, the appearance of resistance to colistin also makes treatment of the Acinetobacter infections very difficult. Antimicrobial peptides (AMP) from the innate immunity hold promise as new alternative antibiotics due to their multiple biological properties. In this study, we characterized the activity and the membrane-perturbing mechanism of bactericidal action of a derivative of a frog-skin AMP, namely Esc(1-21), when used alone or in combination with colistin against multidrug-resistant A. baumannii clinical isolates. We found that the mixture of the two compounds had a synergistic effect in inhibiting the growth and killing of all of the tested strains. When combined at dosages below the minimal inhibitory concentration, the two drugs were also able to slow down the microbial growth and to potentiate the membrane-perturbing effect. To the best of our knowledge, this is the first report showing a synergistic effect between AMPs, i.e., Esc(1-21), and colistin against colistin-resistant A. baumannii clinical isolates, highlighting the potential clinical application of such combinational therapy.<\/jats:p>","DOI":"10.3390\/antibiotics11020234","type":"journal-article","created":{"date-parts":[[2022,2,13]],"date-time":"2022-02-13T20:32:30Z","timestamp":1644784350000},"page":"234","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["The Antimicrobial Peptide Esc(1-21) Synergizes with Colistin in Inhibiting the Growth and in Killing Multidrug Resistant Acinetobacter baumannii Strains"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7933-8407","authenticated-orcid":false,"given":"Federica","family":"Sacco","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine, University of Rome \u201cLa Sapienza\u201d, 00161 Rome, Italy"},{"name":"Clinical Microbiology Laboratory, Sapienza University Hospital Policlinico Umberto I of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"Bitossi","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, University of Rome \u201cLa Sapienza\u201d, 00161 Rome, Italy"},{"name":"Clinical Microbiology Laboratory, Sapienza University Hospital Policlinico Umberto I of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1295-1084","authenticated-orcid":false,"given":"Bruno","family":"Casciaro","sequence":"additional","affiliation":[{"name":"Department of Biochemical Sciences, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Rosa","family":"Loffredo","sequence":"additional","affiliation":[{"name":"Department of Biochemical Sciences, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guendalina","family":"Fabiano","sequence":"additional","affiliation":[{"name":"Department of Biochemical Sciences, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Torrini","sequence":"additional","affiliation":[{"name":"Department of Biochemical Sciences, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia","family":"Raponi","sequence":"additional","affiliation":[{"name":"Clinical Microbiology Laboratory, Sapienza University Hospital Policlinico Umberto I of Rome, 00161 Rome, Italy"},{"name":"Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9665-0811","authenticated-orcid":false,"given":"Giammarco","family":"Raponi","sequence":"additional","affiliation":[{"name":"Clinical Microbiology Laboratory, Sapienza University Hospital Policlinico Umberto I of Rome, 00161 Rome, Italy"},{"name":"Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5991-5868","authenticated-orcid":false,"given":"Maria Luisa","family":"Mangoni","sequence":"additional","affiliation":[{"name":"Department of Biochemical Sciences, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"441","DOI":"10.3389\/fimmu.2017.00441","article-title":"The Immune Response against Acinetobacter baumannii, an Emerging Pathogen in Nosocomial Infections","volume":"8","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1086\/508360","article-title":"Colonization or infection with multidrug-resistant Acinetobacter baumannii may be an independent risk factor for increased mortality","volume":"43","author":"Hershow","year":"2006","journal-title":"Clin. Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"787","DOI":"10.12998\/wjcc.v2.i12.787","article-title":"Antimicrobial resistance in Acinetobacter baumannii: From bench to bedside","volume":"2","author":"Lin","year":"2014","journal-title":"World J. Clin. Cases"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1093\/cid\/civ048","article-title":"Colistin-resistant Acinetobacter baumannii: Beyond carbapenem resistance","volume":"60","author":"Qureshi","year":"2015","journal-title":"Clin. Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1016\/j.cmi.2019.03.014","article-title":"Carbapenem-resistant Acinetobacter baumannii: In pursuit of an effective treatment","volume":"25","author":"Piperaki","year":"2019","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.jgar.2017.09.011","article-title":"Polymyxin susceptibility testing, interpretative breakpoints and resistance mechanisms: An update","volume":"12","author":"Bakthavatchalam","year":"2018","journal-title":"J. Glob. Antimicrob. Resist."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.ijantimicag.2012.09.008","article-title":"Global evolution of multidrug-resistant Acinetobacter baumannii clonal lineages","volume":"41","author":"Zarrilli","year":"2013","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1185\/03007995.2015.1018989","article-title":"Colistin, mechanisms and prevalence of resistance","volume":"31","author":"Bialvaei","year":"2015","journal-title":"Curr. Med. Res. Opin."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/s40121-020-00286-6","article-title":"Cefiderocol: A Novel Agent for the Management of Multidrug-Resistant Gram-Negative Organisms","volume":"9","author":"Wu","year":"2020","journal-title":"Infect. Dis. Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"103887","DOI":"10.1016\/j.micpath.2019.103887","article-title":"Global prevalence of colistin resistance in clinical isolates of Acinetobacter baumannii: A systematic review and meta-analysis","volume":"139","author":"Pormohammad","year":"2020","journal-title":"Microb. Pathog."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1080\/14787210.2020.1705155","article-title":"Antibiotic combination therapy against resistant bacterial infections: Synergy, rejuvenation and resistance reduction","volume":"18","author":"Coates","year":"2020","journal-title":"Expert Rev. Anti. Infect. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1093\/clinids\/4.2.282","article-title":"Antibiotic synergism and antimicrobial combinations in clinical infections","volume":"4","author":"Eliopoulos","year":"1982","journal-title":"Rev. Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1128\/CMR.1.2.139","article-title":"Antibiotic combinations: Should they be tested?","volume":"1","author":"Eliopoulos","year":"1988","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/s41579-018-0141-x","article-title":"Drug combinations: A strategy to extend the life of antibiotics in the 21st century","volume":"17","author":"Tyers","year":"2019","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1097\/MCC.0000000000000235","article-title":"New antibiotics and antimicrobial combination therapy for the treatment of gram-negative bacterial infections","volume":"21","author":"Bassetti","year":"2015","journal-title":"Curr. Opin. Crit. Care"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1128\/CMR.05041-11","article-title":"Combination therapy for treatment of infections with gram-negative bacteria","volume":"25","author":"Tamma","year":"2012","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1093\/infdis\/146.5.691","article-title":"Selection of aminoglycoside-resistant variants of Pseudomonas aeruginosa in an in vivo model","volume":"146","author":"Gerber","year":"1982","journal-title":"J. Infect. Dis."},{"key":"ref_18","first-page":"53","article-title":"Efficacy of single-agent therapy with azlocillin, ticarcillin, and amikacin and beta-lactam\/amikacin combinations for treatment of Pseudomonas aeruginosa bacteremia in granulocytopenic rats","volume":"80","author":"Johnson","year":"1986","journal-title":"Am. J. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1093\/jac\/17.suppl_A.11","article-title":"Emergence of resistance after therapy with antibiotics used alone or combined in a murine model","volume":"17","author":"Pechere","year":"1986","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1007\/s10989-020-10110-x","article-title":"Antimicrobial Peptides as Potential Therapeutic Agents: A Review","volume":"27","author":"Datta","year":"2020","journal-title":"Int. J. Pept. Res. Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4","DOI":"10.2174\/18755305MTAwENDE80","article-title":"Mini Review on Antimicrobial Peptides, Sources, Mechanism and Recent Applications","volume":"27","author":"Boparai","year":"2020","journal-title":"Protein Pept. Lett."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.2174\/0929867326666190722095408","article-title":"The Potential of Frog Skin Peptides for Anti-Infective Therapies: The Case of Esculentin-1a(1-21)NH2","volume":"27","author":"Casciaro","year":"2020","journal-title":"Curr. Med. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2740","DOI":"10.3389\/fmicb.2019.02740","article-title":"Synergy Pattern of Short Cationic Antimicrobial Peptides Against Multidrug-Resistant Pseudomonas aeruginosa","volume":"10","author":"Ruden","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"fov022","DOI":"10.1093\/femsyr\/fov022","article-title":"Synergistic fungicidal activity of the lipopeptide bacillomycin D with amphotericin B against pathogenic Candida species","volume":"15","author":"Tabbene","year":"2015","journal-title":"FEMS Yeast Res."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Casciaro, B., Loffredo, M.R., Cappiello, F., Verrusio, W., Corleto, V.D., and Mangoni, M.L. (2020). Frog Skin-Derived Peptides Against Corynebacterium jeikeium: Correlation between Antibacterial and Cytotoxic Activities. Antibiotics, 9.","DOI":"10.3390\/antibiotics9080448"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1007\/s00018-014-1694-0","article-title":"Esculentin-1a(1-21)NH2: A frog skin-derived peptide for microbial keratitis","volume":"72","author":"Kolar","year":"2015","journal-title":"Cell Mol. Life Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1586\/eri.12.78","article-title":"Colistin: An update on the antibiotic of the 21st century","volume":"10","author":"Biswas","year":"2012","journal-title":"Expert Rev. Anti-Infect. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4971","DOI":"10.1128\/AAC.00834-10","article-title":"Colistin resistance in Acinetobacter baumannii is mediated by complete loss of lipopolysaccharide production","volume":"54","author":"Moffatt","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/1120009X.2020.1794393","article-title":"A systematic review of implications, mechanisms, and stability of in vivo emergent resistance to colistin and tigecycline in Acinetobacter baumannii","volume":"33","author":"Karakonstantis","year":"2021","journal-title":"J. Chemother."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2400","DOI":"10.4314\/ahs.v19i3.13","article-title":"Colistin resistance in Acinetobacter baumannii isolated from critically ill patients: Clinical characteristics, antimicrobial susceptibility and outcome","volume":"19","author":"Elham","year":"2019","journal-title":"Afr. Health Sci."},{"key":"ref_31","first-page":"77","article-title":"Fast and reliable diagnosis of XDR Acinetobacter baumannii meningitis by matrix-assisted laser desorption\/ionization time-of-flight mass spectrometry","volume":"41","author":"Brunetti","year":"2018","journal-title":"New Microbiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.3389\/fmicb.2019.01703","article-title":"Combinatory Therapy Antimicrobial Peptide-Antibiotic to Minimize the Ongoing Rise of Resistance","volume":"10","author":"Machini","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1007\/s12602-018-9465-0","article-title":"Antimicrobial Peptides: The Achilles\u2019 Heel of Antibiotic Resistance?","volume":"11","author":"Lewies","year":"2019","journal-title":"Probiotics Antimicrob. Proteins"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"73","DOI":"10.3389\/fnins.2017.00073","article-title":"Membrane Active Antimicrobial Peptides: Translating Mechanistic Insights to Design","volume":"11","author":"Li","year":"2017","journal-title":"Front. Neurosci."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Jangra, M., Raka, V., and Nandanwar, H. (2020). In Vitro Evaluation of Antimicrobial Peptide Tridecaptin M in Combination with Other Antibiotics against Multidrug Resistant Acinetobacter baumannii. Molecules, 25.","DOI":"10.3390\/molecules25143255"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"104700","DOI":"10.1016\/j.micpath.2020.104700","article-title":"Synergistic effect of two antimicrobial peptides, Nisin and P10 with conventional antibiotics against extensively drug-resistant Acinetobacter baumannii and colistin-resistant Pseudomonas aeruginosa isolates","volume":"150","author":"Jahangiri","year":"2021","journal-title":"Microb. Pathog."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2151","DOI":"10.1038\/s41598-021-81140-8","article-title":"In vitro activity of antimicrobial peptide CDP-B11 alone and in combination with colistin against colistin-resistant and multidrug-resistant Escherichia coli","volume":"11","author":"Witherell","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.2174\/0929866525666181101104649","article-title":"Esculentin-1a Derived Antipseudomonal Peptides: Limited Induction of Resistance and Synergy with Aztreonam","volume":"25","author":"Casciaro","year":"2018","journal-title":"Protein Pept. Lett."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1111\/j.1469-0691.2011.03581.x","article-title":"In vitro activity of several antimicrobial peptides against colistin-susceptible and colistin-resistant Acinetobacter baumannii","volume":"18","author":"Pachon","year":"2012","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1128\/IAI.01362-12","article-title":"Lipopolysaccharide-deficient Acinetobacter baumannii shows altered signaling through host Toll-like receptors and increased susceptibility to the host antimicrobial peptide LL-37","volume":"81","author":"Moffatt","year":"2013","journal-title":"Infect. Immun."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.ijantimicag.2011.12.005","article-title":"Efficacy of six frog skin-derived antimicrobial peptides against colistin-resistant strains of the Acinetobacter baumannii group","volume":"39","author":"Conlon","year":"2012","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"309","DOI":"10.3389\/fchem.2018.00309","article-title":"Synergy Between Proline-Rich Antimicrobial Peptides and Small Molecule Antibiotics Against Selected Gram-Negative Pathogens in vitro and in vivo","volume":"6","author":"Otvos","year":"2018","journal-title":"Front. Chem."},{"key":"ref_43","unstructured":"(2017, February 01). MALDI BIOTYPER. Available online: https:\/\/www.bruker.com\/products\/mass-spectrometry-and-separations\/maldi-biotypersystems.html."},{"key":"ref_44","unstructured":"(2017, September 01). BioEdit Software. Available online: http:\/\/www.mbio.ncsu.edu\/BioEdit\/bioedit.html."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.ijantimicag.2006.01.004","article-title":"Multiplex PCR for genes encoding prevalent OXA carbapenemases in Acinetobacter spp","volume":"27","author":"Woodford","year":"2006","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.ijantimicag.2009.10.014","article-title":"Inclusion of OXA-143 primers in a multiplex polymerase chain reaction (PCR) for genes encoding prevalent OXA carbapenemases in Acinetobacter spp","volume":"35","author":"Higgins","year":"2010","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1111\/j.1469-0691.2007.01759.x","article-title":"Use of sequence-based typing and multiplex PCR to identify clonal lineages of outbreak strains of Acinetobacter baumannii","volume":"13","author":"Turton","year":"2007","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.drup.2012.06.001","article-title":"Insights into the global molecular epidemiology of carbapenem non-susceptible clones of Acinetobacter baumannii","volume":"15","author":"Karah","year":"2012","journal-title":"Drug Resist. Updates"},{"key":"ref_49","unstructured":"(2017, June 01). European Committee on Antimicrobial Susceptibility Testing. Available online: http:\/\/www.eucast.org\/clinical_breakpoints."},{"key":"ref_50","unstructured":"Clinical and Laboratory Standards Institute (2015). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically, Clinical and Laboratory Standards Institute. [10th ed.]. Approved Standard."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1093\/jac\/dki477","article-title":"In vitro antibacterial activities of tigecycline in combination with other antimicrobial agents determined by chequerboard and time-kill kinetic analysis","volume":"57","author":"Petersen","year":"2006","journal-title":"J. Antimicrob. Chemother."}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/11\/2\/234\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:17:23Z","timestamp":1760134643000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/11\/2\/234"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,11]]},"references-count":51,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["antibiotics11020234"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics11020234","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,11]]}}}