{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T15:37:13Z","timestamp":1782401833272,"version":"3.54.5"},"reference-count":47,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,6,19]],"date-time":"2020-06-19T00:00:00Z","timestamp":1592524800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["2018\/29\/N\/ST8\/01043"],"award-info":[{"award-number":["2018\/29\/N\/ST8\/01043"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["2018\/31\/B\/ST8\/03170"],"award-info":[{"award-number":["2018\/31\/B\/ST8\/03170"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004569","name":"Ministerstwo Nauki i Szkolnictwa Wy\u017cszego","doi-asserted-by":"publisher","award":["002\/RID\/2018\/19"],"award-info":[{"award-number":["002\/RID\/2018\/19"]}],"id":[{"id":"10.13039\/501100004569","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Increasing multidrug resistance has led to renewed interest in phage-based therapy. A combination of the bacteriophages and antibiotics presents a promising approach enhancing the phage therapy effectiveness. First, phage candidates for therapy should be deeply characterized. Here we characterize the bacteriophage vB_AbaP_AGC01 that poses antibacterial activity against clinical Acinetobacter baumannii strains. Moreover, besides genomic and phenotypic analysis our study aims to analyze phage\u2013antibiotic combination effectiveness with the use of ex vivo and in vivo models. The phage AGC01 efficiently adsorbs to A. baumannii cells and possesses a bacteriolytic lifecycle resulting in high production of progeny phages (317 \u00b1 20 PFU \u00d7 cell\u22121). The broad host range (50.27%, 93 out of 185 strains) against A. baumannii isolates and the inability of AGC01 to infect other bacterial species show its high specificity. Genomic analysis revealed a high similarity of the AGC01 genome sequence with that of the Friunavirus genus from a subfamily of Autographivirinae. The AGC01 is able to significantly reduce the A. baumannii cell count in a human heat-inactivated plasma blood model (HIP-B), both alone and in combination with antibiotics (gentamicin (GEN), ciprofloxacin (CIP), and meropenem (MER)). The synergistic action was observed when a combination of phage treatment with CIP or MER was used. The antimicrobial activity of AGC01 and phage-antibiotic combinations was confirmed using an in vivo larva model. This study shows the greatest increase in survival of G. mellonella larvae when the combination of phage (MOI = 1) and MER was used, which increased larval survival from 35% to 77%. Hence, AGC01 represents a novel candidate for phage therapy. Additionally, our study suggests that phages and antibiotics can act synergistically for greater antimicrobial effect when used as combination therapy.<\/jats:p>","DOI":"10.3390\/ijms21124390","type":"journal-article","created":{"date-parts":[[2020,6,19]],"date-time":"2020-06-19T12:19:55Z","timestamp":1592569195000},"page":"4390","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":82,"title":["Antibiotics Act with vB_AbaP_AGC01 Phage against Acinetobacter baumannii in Human Heat-Inactivated Plasma Blood and Galleria mellonella Models"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0593-0069","authenticated-orcid":false,"given":"Bart\u0142omiej","family":"Grygorcewicz","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Pomeranian Medical University in Szczecin, Powsta\u0144c\u00f3w Wielkopolskich 72, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7721-1223","authenticated-orcid":false,"given":"Marta","family":"Roszak","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Pomeranian Medical University in Szczecin, Powsta\u0144c\u00f3w Wielkopolskich 72, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7232-4440","authenticated-orcid":false,"given":"Piotr","family":"Golec","sequence":"additional","affiliation":[{"name":"Department of Molecular Virology, Institute of Microbiology, Faculty of Biology, University of Warsaw, Miecznikowa 1, 02-096 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daria","family":"\u015aleboda-Taront","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Pomeranian Medical University in Szczecin, Powsta\u0144c\u00f3w Wielkopolskich 72, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3985-2572","authenticated-orcid":false,"given":"Natalia","family":"\u0141ubowska","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Faculty of Medicine, Medical University of Gdansk; Marii Sk\u0142odowskiej-Curie 3a, 80-210 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martyna","family":"G\u00f3rska","sequence":"additional","affiliation":[{"name":"Department of General Pathology, Pomeranian Medical University in Szczecin, Powsta\u0144c\u00f3w Wielkopolskich 72, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Jursa-Kulesza","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Pomeranian Medical University in Szczecin, Powsta\u0144c\u00f3w Wielkopolskich 72, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5770-926X","authenticated-orcid":false,"given":"Rafa\u0142","family":"Rakoczy","sequence":"additional","affiliation":[{"name":"Institute of Chemical Engineering and Environmental Protection Process, Faculty of Chemical Engineering, West Pomeranian University of Technology, al. Piast\u00f3w 42, 71-065 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2990-0323","authenticated-orcid":false,"given":"Bartosz","family":"Wojciuk","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Immunology, Pomeranian Medical University in Szczecin, Powsta\u0144c\u00f3w Wielkopolskich 72, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3138-1013","authenticated-orcid":false,"given":"Barbara","family":"Do\u0142\u0119gowska","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Pomeranian Medical University in Szczecin, Powsta\u0144c\u00f3w Wielkopolskich 72, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"55","DOI":"10.3389\/fcimb.2017.00055","article-title":"Biology of Acinetobacter baumannii: Pathogenesis, Antibiotic Resistance Mechanisms, and Prospective Treatment Options","volume":"7","author":"Lee","year":"2017","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1089\/mdr.2018.0182","article-title":"Relationship Between Different Resistance Mechanisms and Virulence in Acinetobacter baumannii","volume":"25","author":"Espinal","year":"2019","journal-title":"Microb. Drug Resist."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1128\/AAC.01597-13","article-title":"Biological cost of different mechanisms of colistin resistance and their impact on virulence in Acinetobacter baumannii","volume":"58","author":"Beceiro","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_4","unstructured":"World Health Organization (2017). Global Priority List of Antibiotic-Resistant Bacteria to Guide Research, Discovery, and Development of New Antibiotics, World Health Organization."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1111\/2049-632X.12125","article-title":"Acinetobacter baumannii: Evolution of a global pathogen","volume":"71","author":"Antunes","year":"2014","journal-title":"Pathog. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1016\/j.ijantimicag.2015.03.001","article-title":"Emerging broad-spectrum resistance in Pseudomonas aeruginosa and Acinetobacter baumannii: Mechanisms and epidemiology","volume":"45","author":"Potron","year":"2015","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/j.resmic.2018.05.002","article-title":"Bacteriophage research\u2014What we have learnt and what still needs to be addressed","volume":"169","author":"Kropinski","year":"2018","journal-title":"Res. Microbiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"31","DOI":"10.4161\/bact.1.1.14942","article-title":"Phages in nature","volume":"1","author":"Clokie","year":"2011","journal-title":"Bacteriophage"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2874","DOI":"10.1128\/AAC.49.7.2874-2878.2005","article-title":"Human volunteers receiving Escherichia coli phage T4 orally: A safety test of phage therapy","volume":"49","author":"Bruttin","year":"2005","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Turner, D., Ackermann, H.W., Kropinski, A.M., Lavigne, R., Sutton, J.M., and Reynolds, D.M. (2018). Comparative analysis of 37 Acinetobacter bacteriophages. Viruses, 10.","DOI":"10.3390\/v10010005"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"14140","DOI":"10.1038\/s41598-018-32344-y","article-title":"Enhanced antibacterial effect of the novel T4-like bacteriophage KARL-1 in combination with antibiotics against multi-drug resistant Acinetobacter baumannii","volume":"8","author":"Jansen","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"5113","DOI":"10.1128\/AEM.00306-08","article-title":"Simple method for plating Escherichia coli bacteriophages forming very small plaques or no plaques under standard conditions","volume":"74","author":"Golec","year":"2008","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1128\/AEM.02850-14","article-title":"Burkholderia cepacia complex phage-antibiotic synergy (PAS): Antibiotics stimulate lytic phage activity","volume":"81","author":"Kamal","year":"2015","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Turner, D., Wand, M.E., Briers, Y., Lavigne, R., Sutton, J.M., and Reynolds, D.M. (2017). Characterisation and genome sequence of the lytic Acinetobacter baumannii bacteriophage vB_AbaS_Loki. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0172303"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Farrugia, D.N., Elbourne, L.D.H., Hassan, K.A., Eijkelkamp, B.A., Tetu, S.G., Brown, M.H., Shah, B.S., Peleg, A.Y., Mabbutt, B.C., and Paulsen, I.T. (2013). The Complete Genome and Phenome of a Community-Acquired Acinetobacter baumannii. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0058628"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e01064-17","DOI":"10.1128\/JVI.01064-17","article-title":"Genomic and Biochemical Characterization of Acinetobacter Podophage Petty Reveals a Novel Lysis Mechanism and Tail-Associated Depolymerase Activity","volume":"92","author":"Lessor","year":"2018","journal-title":"J. Virol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"\u0141ubowska, N., Grygorcewicz, B., Kosznik-Kwa\u015bnicka, K., Zauszkiewicz-Pawlak, A., W\u0119grzyn, A., Do\u0142\u0119gowska, B., and Piechowicz, L. (2019). Characterization of the Three New Kayviruses and Their Lytic Activity Against Multidrug-Resistant Staphylococcus aureus. Microorganisms, 7.","DOI":"10.3390\/microorganisms7100471"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Melo, L.D.R., Brand\u00e3o, A., Akturk, E., Santos, S.B., and Azeredo, J. (2018). Characterization of a new Staphylococcus aureus Kayvirus harboring a lysin active against biofilms. Viruses, 10.","DOI":"10.3390\/v10040182"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Szymczak, M., Grygorcewicz, B., Karczewska-Golec, J., Decewicz, P., Pankowski, J.A., Orsz\u00e1gh-Szturo, H., B\u0105cal, P., Do\u0142\u0119gowska, B., and Golec, P. (2020). Characterization of a Unique Bordetella bronchiseptica vB_BbrP_BB8 Bacteriophage and Its Application as an Antibacterial Agent. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041403"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Yang, H., Liang, L., Lin, S., and Jia, S. (2010). Isolation and characterization of a virulent bacteriophage AB1 of Acinetobacter baumannii. BMC Microbiol., 10.","DOI":"10.1186\/1471-2180-10-131"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Lai, M.J., Chang, K.C., Huang, S.W., Luo, C.H., Chiou, P.Y., Wu, C.C., and Lin, N.T. (2016). The tail associated protein of Acinetobacter baumannii phage qab6 is the host specificity determinant possessing exopolysaccharide depolymerase activity. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0153361"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e6173","DOI":"10.7717\/peerj.6173","article-title":"Identification and characterization of capsule depolymerase Dpo48 from Acinetobacter baumannii phage IME200","volume":"7","author":"Liu","year":"2019","journal-title":"PeerJ"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Domingo-Calap, P., Beamud, B., Mora-Quilis, L., Gonz\u00e1lez-Candelas, F., and Sanju\u00e1n, R. (2020). Isolation and Characterization of Two Klebsiella pneumoniae Phages Encoding Divergent Depolymerases. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21093160"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5060","DOI":"10.1111\/1462-2920.13970","article-title":"Ability of phages to infect Acinetobacter calcoaceticus-Acinetobacter baumannii complex species through acquisition of different pectate lyase depolymerase domains","volume":"19","author":"Oliveira","year":"2017","journal-title":"Environ. Microbiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1007\/s11274-009-9991-8","article-title":"Amoxicillin and specific bacteriophage can be used together for eradication of biofilm of Klebsiella pneumoniae B5055","volume":"25","author":"Bedi","year":"2009","journal-title":"World J. Microbiol. Biotechnol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1007\/s12223-011-0039-8","article-title":"The influence of external factors on bacteriophages\u2014Review","volume":"56","year":"2011","journal-title":"Folia Microbiol. (Praha)"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.apsoil.2017.06.020","article-title":"Bacteriophage-mediated reduction of Salmonella Enteritidis in swine slurry","volume":"119","author":"Grygorcewicz","year":"2017","journal-title":"Appl. Soil Ecol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2326","DOI":"10.1038\/s41598-018-20698-2","article-title":"Metals Enhance the Killing of Bacteria by Bacteriophage in Human Blood","volume":"8","author":"Ma","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Blasco, L., Ambroa, A., Lopez, M., Fernandez-Garcia, L., Bleriot, I., Trastoy, R., Ramos-Vivas, J., Coenye, T., Fernandez-Cuenca, F., and Vila, J. (2019). Combined use of the Ab105-2\u03d5\u2206CI lytic mutant phage and different antibiotics in clinical isolates of multi-resistant Acinetobacter baumannii. Microorganisms, 7.","DOI":"10.20944\/preprints201910.0025.v1"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Pletzer, D., Mansour, S.C., and Hancock, R.E.W. (2018). Synergy between conventional antibiotics and anti-biofilm peptides in a murine, sub-cutaneous abscess model caused by recalcitrant ESKAPE pathogens. PLoS Pathog., 14.","DOI":"10.1371\/journal.ppat.1007084"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1093\/jac\/dkr198","article-title":"Wax moth larva (Galleria mellonella): An in vivo model for assessing the efficacy of antistaphylococcal agents","volume":"66","author":"Desbois","year":"2011","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.1128\/AAC.01166-08","article-title":"Experimental bacteriophage therapy increases survival of Galleria mellonella larvae infected with clinically relevant strains of the Burkholderia cepacia complex","volume":"53","author":"Seed","year":"2009","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2253","DOI":"10.1007\/s00705-014-2055-x","article-title":"Efficiency of bacteriophage therapy against Cronobacter sakazakii in Galleria mellonella (greater wax moth) larvae","volume":"159","author":"Abbasifar","year":"2014","journal-title":"Arch. Virol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.ijantimicag.2015.04.005","article-title":"Assessing phage therapy against Pseudomonas aeruginosa using a Galleria mellonella infection model","volume":"46","author":"Beeton","year":"2015","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Jeon, J., Park, J.H., and Yong, D. (2019). Efficacy of bacteriophage treatment against carbapenem-resistant Acinetobacter baumannii in Galleria mellonella larvae and a mouse model of acute pneumonia. BMC Microbiol., 19.","DOI":"10.1186\/s12866-019-1443-5"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1080\/21505594.2015.1135289","article-title":"Galleria mellonella infection models for the study of bacterial diseases and for antimicrobial drug testing","volume":"5594","author":"Tsai","year":"2016","journal-title":"Virulence"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.mib.2019.03.005","article-title":"Stronger together? Perspectives on phage-antibiotic synergy in clinical applications of phage therapy","volume":"51","author":"Segall","year":"2019","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/978-1-60327-164-6_2","article-title":"Bacteriophage enrichment from water and soil","volume":"501","author":"Twest","year":"2009","journal-title":"Methods Mol. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Adriaenssens, E.M., and Rodney Brister, J. (2017). How to name and classify your phage: An informal guide. Viruses, 9.","DOI":"10.1101\/111526"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Mazzocco, A., Waddell, T.E., Lingohr, E., and Johnson, R.P. (2009). Enumeration of Bacteriophages by the Direct Plating Plaque Assay. Bacteriophages, Humana Press.","DOI":"10.1007\/978-1-60327-164-6_8"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Mirzaei, M.K., and Nilsson, A.S. (2015). Isolation of phages for phage therapy: A comparison of spot tests and efficiency of plating analyses for determination of host range and efficacy. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0127606"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/978-1-60327-164-6_15","article-title":"Measurement of the rate of attachment of bacteriophage to cells","volume":"501","author":"Kropinski","year":"2009","journal-title":"Methods Mol. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e12747","DOI":"10.1111\/jfs.12747","article-title":"In-milk inactivation of Escherichia coli O157: H7 by the environmental lytic bacteriophage ECPS-6","volume":"40","author":"Grygorcewicz","year":"2019","journal-title":"J. Food Saf."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1093\/molbev\/msy096","article-title":"MEGA X: Molecular Evolutionary Genetics Analysis across Computing Platforms","volume":"35","author":"Kumar","year":"2018","journal-title":"Mol. Boil. Evol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1093\/bioinformatics\/btg456","article-title":"PHIRE, a deterministic approach to reveal regulatory elements in bacteriophage genomes","volume":"20","author":"Lavigne","year":"2004","journal-title":"Bioinformatics"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1101\/gr.849004","article-title":"WebLogo: A sequence logo generator","volume":"14","author":"Crooks","year":"2004","journal-title":"Genome Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2620","DOI":"10.1093\/bioinformatics\/btq484","article-title":"Circoletto: Visualizing sequence similarity with Circos","volume":"26","author":"Darzentas","year":"2010","journal-title":"Bioinformatics"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/12\/4390\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:41:04Z","timestamp":1760175664000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/12\/4390"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,19]]},"references-count":47,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2020,6]]}},"alternative-id":["ijms21124390"],"URL":"https:\/\/doi.org\/10.3390\/ijms21124390","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,19]]}}}