{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T11:38:03Z","timestamp":1783769883377,"version":"3.55.0"},"reference-count":69,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,17]],"date-time":"2021-11-17T00:00:00Z","timestamp":1637107200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["1233\/18"],"award-info":[{"award-number":["1233\/18"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>We describe the design and attributes of a linear pentapeptide-like derivative (C14(\u03c95)OOc10O) screened for its ability to elicit bactericidal competences of plasma constituents against Gram-negative bacteria (GNB). In simpler culture media, the lipopeptide revealed high aptitudes to sensitize resilient GNB to hydrophobic and\/or efflux-substrate antibiotics, whereas in their absence, C14(\u03c95)OOc10O only briefly delayed bacterial proliferation. Instead, at low micromolar concentrations, the lipopeptide has rapidly lowered bacterial proton and ATP levels, although significantly less than upon treatment with its bactericidal analog. Mechanistic studies support a two-step scenario providing a plausible explanation for the lipopeptide\u2019s biological outcomes against GNB: initially, C14(\u03c95)OOc10O permeabilizes the outer membrane similarly to polymyxin B, albeit in a manner not necessitating as much LPS-binding affinity. Subsequently, C14(\u03c95)OOc10O would interact with the inner membrane gently yet intensively enough to restrain membrane-protein functions such as drug efflux and\/or ATP generation, while averting the harsher inner membrane perturbations that mediate the fatal outcome associated with bactericidal peers. Preliminary in vivo studies where skin wound infections were introduced in mice, revealed a significant efficacy in affecting bacterial viability upon topical treatment with creams containing C14(\u03c95)OOc10O, whereas synergistic combination therapies were able to secure the pathogen\u2019s eradication. Further, capitalizing on the finding that C14(\u03c95)OOc10O plasma-potentiating concentrations were attainable in mice blood at sub-maximal tolerated doses, we used a urinary tract infection model to acquire evidence for the lipopeptide\u2019s systemic capacity to reduce the kidney\u2019s bacterial loads. Collectively, the data establish the role of C14(\u03c95)OOc10O as a compelling antibacterial potentiator and suggest its drug-like potential.<\/jats:p>","DOI":"10.3390\/pharmaceutics13111947","type":"journal-article","created":{"date-parts":[[2021,11,17]],"date-time":"2021-11-17T09:16:11Z","timestamp":1637140571000},"page":"1947","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Mechanistic Studies of Antibiotic Adjuvants Reducing Kidney\u2019s Bacterial Loads upon Systemic Monotherapy"],"prefix":"10.3390","volume":"13","author":[{"given":"Fadia","family":"Zaknoon","sequence":"first","affiliation":[{"name":"Department of Biotechnology and Food Engineering, Technion-Israel Institute of Technology, Haifa 3200003, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ohad","family":"Meir","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Food Engineering, Technion-Israel Institute of Technology, Haifa 3200003, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2277-1071","authenticated-orcid":false,"given":"Amram","family":"Mor","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Food Engineering, Technion-Israel Institute of Technology, Haifa 3200003, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1038\/s41579-019-0288-0","article-title":"The global preclinical antibacterial pipeline","volume":"18","author":"Theuretzbacher","year":"2020","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.mib.2016.05.005","article-title":"Treatment of Gram-negative bacterial infections by potentiation of antibiotics","volume":"33","author":"Zabawa","year":"2016","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1016\/j.tim.2016.06.009","article-title":"Antibiotic Adjuvants: Rescuing Antibiotics from Resistance","volume":"24","author":"Wright","year":"2016","journal-title":"Trends Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"17001","DOI":"10.1038\/nmicrobiol.2017.1","article-title":"Mechanisms of envelope permeability and antibiotic influx and efflux in Gram-negative bacteria","volume":"2","author":"Masi","year":"2017","journal-title":"Nat. Microbiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"6379","DOI":"10.1016\/j.bmc.2016.06.044","article-title":"A Gestalt approach to Gram-negative entry","volume":"24","author":"Silver","year":"2016","journal-title":"Bioorg. Med. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"eaau5480","DOI":"10.1126\/science.aau5480","article-title":"Antimicrobial peptides: Application informed by evolution","volume":"368","author":"Lazzaro","year":"2020","journal-title":"Science"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1038\/s41573-019-0058-8","article-title":"Antimicrobial host defence peptides: Functions and clinical potential","volume":"19","author":"Mookherjee","year":"2020","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.cbpa.2017.03.014","article-title":"Host defense antimicrobial peptides as antibiotics: Design and application strategies","volume":"38","author":"Mishra","year":"2017","journal-title":"Curr. Opin. Chem. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4076","DOI":"10.1021\/bi100378m","article-title":"Probing the \u201c Charge Cluster Mechanism \u201d in Amphipathic Helical Cationic","volume":"49","author":"Epand","year":"2010","journal-title":"Biochemistry"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"14346","DOI":"10.1021\/ja8062327","article-title":"Bacterial membranes as predictors of antimicrobial potency","volume":"130","author":"Epand","year":"2008","journal-title":"J. Am. Chem. Soc."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"6597","DOI":"10.1073\/pnas.86.17.6597","article-title":"Magainins and the disruption of membrane-linked free-energy transduction","volume":"86","author":"Westerhoff","year":"1989","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1016\/j.bbamem.2015.10.022","article-title":"Controlling bacterial infections by inhibiting proton-dependent processes","volume":"1858","author":"Kaneti","year":"2015","journal-title":"BBA Biomembr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4192","DOI":"10.1128\/jb.176.13.4192-4195.1994","article-title":"Reconstitution of Energy-Linked Activities of the Solubilized F1F0 ATP Synthase from Bacillus subtilis","volume":"176","author":"Hicks","year":"1994","journal-title":"J. Bacteriol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1073\/pnas.1319900111","article-title":"Small cationic antimicrobial peptides delocalize peripheral membrane proteins","volume":"111","author":"Wenzel","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3708","DOI":"10.1128\/AAC.00380-10","article-title":"Depolarization, bacterial membrane composition, and the antimicrobial action of ceragenins","volume":"54","author":"Epand","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Reens, A.L., Crooks, A.L., Su, C.C., Nagy, T.A., Reens, D.L., Podoll, J.D., Edwards, M.E., Yu, E.W., and Detweiler, C.S. (2018). A cell-based infection assay identifies efflux pump modulators that reduce bacterial intracellular load. PLoS Pathog., 14.","DOI":"10.1371\/journal.ppat.1007115"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/j.bbamem.2016.01.011","article-title":"Peptides with dual mode of action: Killing bacteria and preventing endotoxin-induced sepsis","volume":"1858","author":"Brandenburg","year":"2016","journal-title":"BBA Biomembr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4834","DOI":"10.1096\/fj.13-237610","article-title":"Simultaneous breakdown of multiple antibiotic resistance mechanisms in S. aureus","volume":"27","author":"Kaneti","year":"2013","journal-title":"FASEB J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1016\/j.bbamem.2019.04.002","article-title":"Sub-inhibitory membrane damage undermines Staphylococcus aureus virulence","volume":"1861","author":"Hershkovits","year":"2019","journal-title":"BBA Biomembr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1128\/mr.56.3.395-411.1992","article-title":"Agents That Increase the Permeability of the Outer Membrane","volume":"56","author":"Vaara","year":"1992","journal-title":"Microbiol. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"236","DOI":"10.3389\/fcimb.2019.00236","article-title":"Repurposing azithromycin and rifampicin against gram-negative pathogens by combination with peptidomimetics","volume":"9","author":"Baker","year":"2019","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1016\/j.ebiom.2015.05.021","article-title":"Azithromycin Synergizes with Cationic Antimicrobial Peptides to Exert Bactericidal and Therapeutic Activity Against Highly Multidrug-Resistant Gram-Negative Bacterial Pathogens","volume":"2","author":"Lin","year":"2015","journal-title":"EBioMedicine"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1038\/303526a0","article-title":"Sensitization of Gram-negative bacteria to antibiotics and complement by a nontoxic oligopeptide","volume":"303","author":"Vaara","year":"1983","journal-title":"Nature"},{"key":"ref_24","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_25","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1128\/mr.47.1.46-83.1983","article-title":"Bactericidal and bacteriolytic activity of serum against gram-negative bacteria","volume":"47","author":"Taylor","year":"1983","journal-title":"Microbiol. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1038\/nbt1309","article-title":"Improved antimicrobial peptides based on acyl-lysine oligomers","volume":"25","author":"Radzishevsky","year":"2007","journal-title":"Nat. Biotechnol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1016\/j.chembiol.2009.11.012","article-title":"Design and Characterization of a Broad -Spectrum Bactericidal Acyl-lysyl Oligomer","volume":"16","author":"Livne","year":"2009","journal-title":"Chem. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.chembiol.2008.03.006","article-title":"Structure-Activity Relationships of Antibacterial Acyl-Lysine Oligomers","volume":"15","author":"Radzishevsky","year":"2008","journal-title":"Chem. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1599","DOI":"10.1093\/infdis\/jix119","article-title":"Sensitization of Gram-Negative Bacilli to Host Antibacterial Proteins","volume":"215","author":"Jammal","year":"2017","journal-title":"J. Infect. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1096\/fj.201700652r","article-title":"Eliciting improved antibacterial efficacy of host proteins in the presence of antibiotics","volume":"32","author":"Jammal","year":"2018","journal-title":"FASEB J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"srep09216","DOI":"10.1038\/srep09216","article-title":"Sensitization of Gram-negative bacteria to rifampin and OAK combinations","volume":"5","author":"Jammal","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-017-02373-0","article-title":"A broad-spectrum bactericidal lipopeptide with anti-biofilm properties","volume":"7","author":"Meir","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1904","DOI":"10.1096\/fj.09-149427","article-title":"A miniature mimic of host defense peptides with systemic antibacterial efficacy","volume":"24","author":"Sarig","year":"2010","journal-title":"FASEB J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1128\/jb.178.1.306-308.1996","article-title":"AcrAB efflux pump plays a major role in the antibiotic resistance phenotype of Escherichia coli multiple-antibiotic-resistance (Mar) mutants","volume":"178","author":"Okusu","year":"1996","journal-title":"J. Bacteriol."},{"key":"ref_35","unstructured":"Redfield, R. (2019). Antibiotic Resistance Threats in the United States."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3422","DOI":"10.1128\/AAC.00010-09","article-title":"Antibacterial properties and mode of action of a short acyl-lysyl oligomer","volume":"53","author":"Zaknoon","year":"2009","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4827","DOI":"10.1128\/AAC.00511-12","article-title":"Antibacterial properties of an oligo-acyl-lysyl hexamer targeting gram-negative species","volume":"56","author":"Zaknoon","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1128\/AAC.35.7.1309","article-title":"Interaction of aminoglycosides with the outer membranes and purified lipopolysaccharide and OmpF porin of Escherichia coli","volume":"35","author":"Hancock","year":"1991","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2969","DOI":"10.1128\/AAC.44.11.2969-2978.2000","article-title":"Stages of polymyxin B interaction with the Escherichia coli cell envelope","volume":"44","author":"Daugelavicius","year":"2000","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1038\/ja.2016.146","article-title":"Development of new polymyxin derivatives for multi-drug resistant Gram-negative infections","volume":"70","author":"Brown","year":"2017","journal-title":"J. Antibiot."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/0022-1759(88)90414-0","article-title":"Concurrent assessment of inner and outer membrane permeabilization and bacteriolysis in E. coli by multiple-wavelength spectrophotometry","volume":"108","author":"Lehrer","year":"1988","journal-title":"J. Immunol. Methods"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1128\/AAC.29.3.496","article-title":"Interaction of polycationic antibiotics with Pseudomonas aeruginosa Lipopolysaccharide and lipid A studied by using dansyl-polymyxin","volume":"29","author":"Moore","year":"1986","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4063","DOI":"10.1128\/AAC.03001-15","article-title":"Antimicrobial peptide P60.4Ac-containing creams and gel for eradication of methicillin-resistant Staphylococcus aureus from cultured skin and airway epithelial surfaces","volume":"60","author":"Haisma","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1002\/med.21542","article-title":"Antimicrobial peptides: Promising alternatives in the post feeding antibiotic era","volume":"39","author":"Wang","year":"2019","journal-title":"Med. Res. Rev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1002\/marc.201200534","article-title":"Rationally Designed \u03b1 -Helical Broad-Spectrum Antimicrobial Peptides with Idealized Facial Amphiphilicity","volume":"34","author":"Wiradharma","year":"2013","journal-title":"Macromol. Rapid Commun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1016\/j.colsurfb.2016.02.003","article-title":"Role of amphipathicity and hydrophobicity in the balance between hemolysis and peptide-membrane interactions of three related antimicrobial peptides","volume":"141","author":"Hollmann","year":"2016","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3229","DOI":"10.1128\/AAC.00405-08","article-title":"Novel polymyxin derivatives carrying only three positive charges are effective antibacterial agents","volume":"52","author":"Vaara","year":"2008","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3341","DOI":"10.1128\/AAC.01439-09","article-title":"A novel polymyxin derivative that lacks the fatty acid tail and carries only three positive charges has strong synergism with agents excluded by the intact outer membrane","volume":"54","author":"Vaara","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"11498","DOI":"10.1074\/jbc.M806587200","article-title":"Interactions of lipopolysaccharide and polymyxin studied by NMR spectroscopy","volume":"284","author":"Mares","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_50","unstructured":"Clinical and Laboratory Standards Institute M100-S26 (2015). Performance Standards for Antimicrobial Susceptibility Testing, CLSI. [26th ed.]. Approved Standard."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/AAC.00200-17","article-title":"Potentiation of antibiotic activity by a novel cationic peptide: Potency and spectrum of activity of SPR741","volume":"61","author":"Corbett","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"76","DOI":"10.2174\/1568026615666150703121009","article-title":"Non-Membrane Permeabilizing Modes of Action of Antimicrobial Peptides on Bacteria","volume":"16","author":"Scocchi","year":"2015","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"8173","DOI":"10.1073\/pnas.1509743112","article-title":"Antibiotic efficacy is linked to bacterial cellular respiration","volume":"112","author":"Lobritz","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"7235","DOI":"10.1021\/bi9826299","article-title":"Mechanism of interaction of different classes of cationic antimicrobial peptides with planar bilayers and with the cytoplasmic membrane of Escherichia coli","volume":"38","author":"Wu","year":"1999","journal-title":"Biochemistry"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1146\/annurev.biochem.66.1.717","article-title":"The ATP synthase\u2014A splendid molecular machine","volume":"66","author":"Boyer","year":"1997","journal-title":"Annu. Rev. Biochem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.cmet.2018.11.002","article-title":"New Advances in Adaptive Thermogenesis: UCP1 and Beyond","volume":"29","author":"Chouchani","year":"2019","journal-title":"Cell Metab."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/s41579-018-0048-6","article-title":"Multidrug efflux pumps: Structure, function and regulation","volume":"16","author":"Du","year":"2018","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1073\/pnas.95.4.1829","article-title":"Modulation of Neisseria gonorrhoeae susceptibility to vertebrate antibacterial peptides due to a member of the resistance\/nodulation\/division efflux pump family","volume":"95","author":"Shafer","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"7190","DOI":"10.1073\/pnas.96.13.7190","article-title":"Bypassing the periplasm: Reconstitution of the AcrAB multidrug efflux pump of Escherichia coli","volume":"96","author":"Zgurskaya","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3818","DOI":"10.1096\/fj.13-227942","article-title":"Sensitization of gram-negative bacteria by targeting the membrane potential","volume":"27","author":"Goldberg","year":"2013","journal-title":"FASEB J."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1101\/cshperspect.a025288","article-title":"Polymyxin: Alternative Mechanisms of Action","volume":"6","author":"Trimble","year":"2016","journal-title":"Cold Spring Harb Perspect. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1146\/annurev.mi.38.100184.001321","article-title":"Alterations in structure of the cell envelope","volume":"38","author":"Hancock","year":"1984","journal-title":"Ann. Rev. Microbiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"12866","DOI":"10.1021\/bi034514x","article-title":"Analysis of Membrane-Binding Properties of Dermaseptin Analogues: Relationships between Binding and Cytotoxicity","volume":"42","author":"Gaidukov","year":"2003","journal-title":"Biochemistry"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1038\/nrmicro3380","article-title":"V Molecular mechanisms of antibiotic resistance","volume":"13","author":"Blair","year":"2015","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"386","DOI":"10.4049\/jimmunol.1102162","article-title":"Pseudomonas aeruginosa Alkaline Protease Blocks Complement Activation via the Classical and Lectin Pathways","volume":"188","author":"Laarman","year":"2012","journal-title":"J. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1111\/exd.12929","article-title":"Antimicrobial peptides and wound healing: Biological and therapeutic considerations","volume":"25","author":"Mangoni","year":"2016","journal-title":"Exp. Dermatol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fphar.2018.00281","article-title":"Antimicrobial peptides and their therapeutic potential for bacterial skin infections and wounds","volume":"9","author":"Pfalzgraff","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1128\/AAC.33.9.1531","article-title":"In vitro and in vivo activities of clarithromycin against Mycobacterium avium","volume":"33","author":"Fernandes","year":"1989","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1038\/s41467-020-14906-9","article-title":"Melittin-lipid nanoparticles target to lymph nodesand elicit a systemic anti-tumor immune response","volume":"11","author":"Xiang","year":"2020","journal-title":"Nat. Commun."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/13\/11\/1947\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:31:35Z","timestamp":1760167895000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/13\/11\/1947"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,17]]},"references-count":69,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["pharmaceutics13111947"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics13111947","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,17]]}}}