{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:10:36Z","timestamp":1790856636435,"version":"4.1.0"},"reference-count":55,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,9,28]],"date-time":"2025-09-28T00:00:00Z","timestamp":1759017600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000181","name":"Air Force Office of Scientific Research","doi-asserted-by":"publisher","award":["FA9550-14-1-0153"],"award-info":[{"award-number":["FA9550-14-1-0153"]}],"id":[{"id":"10.13039\/100000181","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institute of Health","award":["R01AI177563"],"award-info":[{"award-number":["R01AI177563"]}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background\/Objectives: Covalent conjugation of an antibiotic vancomycin (VCM) moiety and a photosensitizing mesochlorin (mChlPd) unit into one molecular entity may present the potential to produce the combinatorial effect of both antibacterial photodynamic therapeutic (aPDT) and antibiotic activities. Our recent study indicated that a short linkage of &lt;4 (C\u2212C\/or C\u2212N) bond distances between these two moieties resulted in significant steric hindrance due to the bulky VCM, which greatly reduces the accessibility of the agent to the cell surface of methicillin-resistant Staphylococcus aureus (MRSA). The observed aPDT efficacy was found to be minimal. Here, we report that the revision of this linkage, via an EG10 unit using identical synthetic procedures, was able to resolve the issue. Methods: Accordingly, the corresponding combinatorial aPDT\u2212antibiotic compound, consisting of two covalently bonded quaternary ammonium pentacationic arms on the mesochlorin chromophore core, designated as VCMe-mChlPd-N10+ (LC40e+), was prepared for applications in antibacterial photodynamic inactivation (aPDI) activity. It was selected to investigate its enhanced binding and targeting ability to the surface of Gram-positive MRSA cells. Subsequent antibacterial photodynamic therapeutic (aPDT) activity to inactivate MRSA was investigated to substantiate the corresponding cell-surface binding effect on the efficacy of aPDT. Results: We found that the covalent combination of 10 positive charges and an MRSA-targeting vancomycin (VCM) moiety in a conjugated structure, functioning as an antibiotic\u2013decacationic photosensitizing agent (Abx-dcPS), was capable of largely improving the MRSA cell-targeting efficiency. Importantly, variation in the chain length of the oligo(ethylene glycol) linker of VCMe-mChlPd-N10+, which was sufficiently long enough to properly separate the photoactive mesochlorin ring moiety from the VCM moiety within the molecular structure, resulted in significantly enhanced aPDT activity. The new conjugate provided nearly complete eradication (&gt;6.5-log10 colony-forming units (CFU) reduction) of MRSA cells in vitro. The aPDT efficacy followed the order Abx-dcPS (combinatorial decacationic) &gt; dcPS (decacationic) &gt;&gt; nPS (nonionic). This order was also verified by the relative physical binding trend of these PSs using either nPS-, dcPS-, or Abx-dcPS-pretreated and pre-fixed MRSA cells in investigations of fluorescent confocal microscopy, UV\u2013vis fluorescence spectroscopy, and transmission electron microscopy (TEM). Conclusions: Furthermore, the molecular conjugate of Abx-dcPS may provide covalent co-delivery of two drug components concurrently, which might also serve as an effective antibiotic agent after aPDT and potentially prevent the reoccurrence of MRSA-induced infection.<\/jats:p>","DOI":"10.3390\/antibiotics14100978","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T16:43:54Z","timestamp":1759250634000},"page":"978","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Selective Targeting and Enhanced Photodynamic Inactivation of Methicillin-Resistant Staphylococcus aureus (MRSA) by a Decacationic Vancomycin\u2013Mesochlorin Conjugate"],"prefix":"10.3390","volume":"14","author":[{"given":"He","family":"Yin","sequence":"first","affiliation":[{"name":"Department of Chemistry, University of Massachusetts Lowell, Lowell, MA 01854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojing","family":"Liu","sequence":"additional","affiliation":[{"name":"Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA"},{"name":"Institute of Photomedicine, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai 200443, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Massachusetts Lowell, Lowell, MA 01854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8960-8896","authenticated-orcid":false,"given":"Tianhong","family":"Dai","sequence":"additional","affiliation":[{"name":"Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0097-5118","authenticated-orcid":false,"given":"Long Y.","family":"Chiang","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Massachusetts Lowell, Lowell, MA 01854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1128\/JCM.02352-08","article-title":"Presence and molecular epidemiology of virulence factors in methicillin-resistant Staphylococcus aureus strains colonizing and infecting soldiers","volume":"47","author":"Ellis","year":"2009","journal-title":"J. Clin. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1099\/jmm.0.043513-0","article-title":"Current concepts on the virulence mechanisms of meticillin-resistant Staphylococcus aureus","volume":"61","author":"Watkins","year":"2012","journal-title":"J. Med. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Lacey, K.A., Geoghegan, J.A., and McLoughlin, R.M. (2016). The Role of Staphylococcus aureus Virulence Factors in Skin Infection and Their Potential as Vaccine Antigens. Pathogens, 5.","DOI":"10.3390\/pathogens5010022"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1073\/pnas.1814265116","article-title":"Sequential evolution of virulence and resistance during clonal spread of community-acquired methicillin-resistant Staphylococcus aureus","volume":"116","author":"Copin","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_5","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_6","doi-asserted-by":"crossref","unstructured":"Harkins, C.P., Pichon, B., Doumith, M., Parkhill, J., Westh, H., Tomasz, A., de Lencastre, H., Bentley, S.D., Kearns, A.M., and Holden, M.T.G. (2017). Methicillin-resistant Staphylococcus aureus emerged long before the introduction of methicillin into clinical practice. Genome Biol., 18.","DOI":"10.1186\/s13059-017-1252-9"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"117","DOI":"10.3934\/microbiol.2019.2.117","article-title":"Methicillin-resistant Staphylococcus aureus (MRSA) and anti-MRSA activities of extracts of some medicinal plants: A brief review","volume":"5","author":"Okwu","year":"2019","journal-title":"AIMS Microbiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1016\/j.coph.2008.08.001","article-title":"New agents in development for the treatment of bacterial infections","volume":"8","author":"Abbanat","year":"2008","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1517\/13543780903505092","article-title":"Newer antibacterial drugs for a new century","volume":"19","author":"Devasahayam","year":"2010","journal-title":"Expert. Opin. Investig. Drugs"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3","DOI":"10.4103\/2229-516X.112229","article-title":"Recent advances in antibacterial drugs","volume":"3","author":"Rai","year":"2013","journal-title":"Int. J. Appl. Basic. Med. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1039\/b311900a","article-title":"Photodynamic therapy: A new antimicrobial approach to infectious disease?","volume":"3","author":"Hamblin","year":"2004","journal-title":"Photochem. Photobiol. Sci."},{"key":"ref_12","first-page":"158","article-title":"Antimicrobial Photodynamic Therapy: A New Therapeutic Option to Combat Infections","volume":"03","author":"Rosa","year":"2014","journal-title":"J. Med. Microb. Diagn."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"5108","DOI":"10.1039\/D3BM00730H","article-title":"Development of organic photosensitizers for antimicrobial photodynamic therapy","volume":"11","author":"Zhou","year":"2023","journal-title":"Biomater. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.mib.2016.06.008","article-title":"Antimicrobial photodynamic inactivation: A bright new technique to kill resistant microbes","volume":"33","author":"Hamblin","year":"2016","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"91","DOI":"10.3390\/md8010091","article-title":"Antimicrobial photodynamic therapy: Study of bacterial recovery viability and potential development of resistance after treatment","volume":"8","author":"Tavares","year":"2010","journal-title":"Mar. Drugs"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1039\/b200977c","article-title":"Photoinactivation of bacterial strains involved in periodontal diseases sensitized by porphycene-polylysine conjugates","volume":"1","author":"Lauro","year":"2002","journal-title":"Photochem. Photobiol. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mib.2014.06.008","article-title":"Reactive oxygen species and the bacterial response to lethal stress","volume":"21","author":"Zhao","year":"2014","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"10064","DOI":"10.1073\/pnas.1901730116","article-title":"Post-stress bacterial cell death mediated by reactive oxygen species","volume":"116","author":"Hong","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1042\/BJ20150942","article-title":"New photosensitizers for photodynamic therapy","volume":"473","author":"Abrahamse","year":"2016","journal-title":"Biochem. J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"81591","DOI":"10.18632\/oncotarget.20189","article-title":"Porphyrin photosensitizers in photodynamic therapy and its applications","volume":"8","author":"Kou","year":"2017","journal-title":"Oncotarget"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1039\/C7CS00594F","article-title":"Supramolecular photosensitizers rejuvenate photodynamic therapy","volume":"47","author":"Li","year":"2018","journal-title":"Chem. Soc. Rev."},{"key":"ref_22","first-page":"25","article-title":"Photodynamic therapy in cancer treatment\u2014An update review","volume":"5","author":"Terra","year":"2019","journal-title":"J. Cancer Metastasis Treat."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1900132","DOI":"10.1002\/adhm.201900132","article-title":"Photosensitizers for Photodynamic Therapy","volume":"8","author":"Lan","year":"2019","journal-title":"Adv. Heal. Mater."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Gallardo-Villagr\u00e1n, M., Leger, D.Y., Liagre, B., and Therrien, B. (2019). Photosensitizers Used in the Photodynamic Therapy of Rheumatoid Arthritis. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20133339"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/j.nano.2013.11.014","article-title":"Photodynamic therapy with decacationic (60)fullerene monoadducts: Effect of a light absorbing electron-donor antenna and micellar formulation","volume":"10","author":"Yin","year":"2014","journal-title":"Nanomedicine"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1016\/j.nano.2012.09.005","article-title":"Photoinduced electron-transfer mechanisms for radical-enhanced photodynamic therapy mediated by water-soluble decacationic C70 and C84O2 Fullerene Derivatives","volume":"9","author":"Sperandio","year":"2013","journal-title":"Nanomed. Nanotech. Biol. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.freeradbiomed.2014.10.514","article-title":"Antimicrobial photodynamic inactivation with decacationic functionalized fullerenes: Oxygen-independent photokilling in presence of azide and new mechanistic insights","volume":"79","author":"Yin","year":"2015","journal-title":"Free Radic. Biol. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.ejmech.2013.01.052","article-title":"Synthesis of decacationic (60)fullerene decaiodides giving photoinduced production of superoxide radicals and effective PDT-mediation on antimicrobial photoinactivation","volume":"63","author":"Wang","year":"2013","journal-title":"Eur. J. Med. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1039\/c8pp00452h","article-title":"Sodium nitrite potentiates antimicrobial photodynamic inactivation: Possible involvement of peroxynitrate","volume":"18","author":"Huang","year":"2019","journal-title":"Photochem. Photobiol. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1111\/mmi.12061","article-title":"Escherichia coli DNA polymerase III is responsible for the high level of spontaneous mutations in mutT strains","volume":"86","author":"Yamada","year":"2012","journal-title":"Mol. Microbiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"14170","DOI":"10.1002\/chem.201102195","article-title":"Molecular interactions between glycopeptide vancomycin and bacterial cell wall peptide analogues","volume":"17","author":"Xing","year":"2011","journal-title":"Chemistry"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1021\/acsomega.7b01483","article-title":"Insights into Key Interactions between Vancomycin and Bacterial Cell Wall Structures","volume":"3","author":"Wang","year":"2018","journal-title":"ACS Omega"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1111\/j.1751-1097.1991.tb08468.x","article-title":"Chlorin and porphyrin derivatives as potential photosensitizers in photodynamic therapy","volume":"53","author":"Pandey","year":"1991","journal-title":"Photochem. Photobiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"293","DOI":"10.5978\/islsm.27_18-RA-01","article-title":"Photosensitizers in antibacterial photodynamic therapy: An overview","volume":"27","author":"Ghorbani","year":"2018","journal-title":"Laser Ther."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1128\/AAC.39.3.781","article-title":"Dimerization and membrane anchors in extracellular targeting of vancomycin group antibiotics","volume":"39","author":"Beauregard","year":"1995","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4581","DOI":"10.1021\/ja00090a006","article-title":"Glycopeptide antibiotic activity and the possible role of dimerization: A model for biological signaling","volume":"116","author":"Mackay","year":"1994","journal-title":"J. Am. Chem. Soc."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1039\/c7pp00389g","article-title":"Progressive cationic functionalization of chlorin derivatives for antimicrobial photodynamic inactivation and related vancomycin conjugates","volume":"17","author":"Huang","year":"2018","journal-title":"Photochem. Photobiol. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4274","DOI":"10.1021\/jm3000664","article-title":"Synthesis and photodynamic effect of new highly photostable decacationically armed (60)- and (70)fullerene decaiodide monoadducts to target pathogenic bacteria and cancer cells","volume":"55","author":"Wang","year":"2012","journal-title":"J. Med. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1111\/j.1751-1097.1978.tb07643.x","article-title":"Solvent Effect on Photosensitized Oxidation of Iodide Ion by Anthracene Sulphonates","volume":"27","author":"Gupta","year":"1978","journal-title":"Photochem. Photobiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1021\/ja047018k","article-title":"A design of fluorescent probes for superoxide based on a nonredox mechanism","volume":"127","author":"Maeda","year":"2005","journal-title":"J. Am. Chem. Soc."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1586\/14787210.2013.811861","article-title":"Photodynamic inactivation of biofilm: Taking a lightly colored approach to stubborn infection","volume":"11","author":"Avci","year":"2013","journal-title":"Expert. Rev. Anti Infect. Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.apsb.2017.09.003","article-title":"An updated overview on the development of new photosensitizers for anticancer photodynamic therapy","volume":"8","author":"Zhang","year":"2018","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1016\/j.biopha.2018.07.049","article-title":"Photodynamic therapy\u2014Mechanisms, photosensitizers and combinations","volume":"106","author":"Kwiatkowski","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1093\/jac\/dkg228","article-title":"Aspects of the antimicrobial mechanisms of action of a polyquaternium and an amidoamine","volume":"51","author":"Codling","year":"2003","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1099\/mic.0.27526-0","article-title":"Evidence of a charge-density threshold for optimum efficiency of biocidal cationic surfaces","volume":"151","author":"Bouloussa","year":"2005","journal-title":"Microbiology"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Kamaruzzaman, N.F., Tan, L.P., Hamdan, R.H., Choong, S.S., Wong, W.K., Gibson, A.J., Chivu, A., and Pina, M.F. (2019). Antimicrobial Polymers: The Potential Replacement of Existing Antibiotics?. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20112747"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1016\/j.chembiol.2005.08.014","article-title":"Cationic fullerenes are effective and selective antimicrobial photosensitizers","volume":"12","author":"Tegos","year":"2005","journal-title":"Chem. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1039\/c8pp00195b","article-title":"Fullerenes as photosensitizers in photodynamic therapy: Pros and cons","volume":"17","author":"Hamblin","year":"2018","journal-title":"Photochem. Photobiol. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"253","DOI":"10.2217\/nnm.13.22","article-title":"Antimicrobial photodynamic therapy with decacationic monoadducts and bisadducts of (70)fullerene: In vitro and in vivo studies","volume":"9","author":"Huang","year":"2014","journal-title":"Nanomedicine"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"603","DOI":"10.2217\/nnm.14.131","article-title":"Potentiation of antimicrobial photodynamic inactivation mediated by a cationic fullerene by added iodide: In vitro and in vivo studies","volume":"10","author":"Zhang","year":"2015","journal-title":"Nanomedicine"},{"key":"ref_51","first-page":"694","article-title":"The use of vancomycin with its therapeutic and adverse effects: A review","volume":"19","author":"Bruniera","year":"2015","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_52","first-page":"63","article-title":"A comparative study of M.I.C evaluator test with the broth microdilution method for antimicrobial susceptibility testing of Enterobacter cloacae isolated from cooked food","volume":"27","author":"Nyenje","year":"2014","journal-title":"Pak. J. Pharm. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1562\/0031-8655(2002)075<0051:RCOWIB>2.0.CO;2","article-title":"Rapid control of wound infections by targeted photodynamic therapy monitored by in vivo bioluminescence imaging","volume":"75","author":"Hamblin","year":"2002","journal-title":"Photochem. Photobiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.1039\/c2pp25113b","article-title":"Comparative photodynamic inactivation of antibiotic resistant bacteria by first and second generation cationic photosensitizers","volume":"11","author":"Costa","year":"2012","journal-title":"Photochem. Photobiol. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.jphotobiol.2016.02.021","article-title":"Synthesis and properties of 5,10,15,20-tetrakis [4-(3-N,N-dimethylaminopropoxy)phenyl] chlorin as potential broad-spectrum antimicrobial photosensitizers","volume":"158","author":"Ferreyra","year":"2016","journal-title":"J. Photochem. Photobiol. B Biol."}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/14\/10\/978\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T16:48:27Z","timestamp":1759250907000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/14\/10\/978"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,28]]},"references-count":55,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["antibiotics14100978"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics14100978","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,28]]}}}