{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:15:27Z","timestamp":1787062527067,"version":"build-2736575974"},"reference-count":99,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T00:00:00Z","timestamp":1724803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The growth of (multi)drug resistance in bacteria is among the most urgent global health issues. Monocationic amphiphilic \u03b1-hydrazido acid derivatives are structurally simple mimics of antimicrobial peptides (AMPs) with fewer drawbacks. Their mechanism of membrane permeabilization at subtoxic concentrations was found to begin with an initial electrostatic attraction of isolated amphiphile molecules to the phospholipid heads, followed by a rapid insertion of the apolar portions. As the accumulation into the bilayer proceeded, the membrane increased its fluidity and permeability without being subjected to major structural damage. After having ascertained that \u03b1-hydrazido acid amphiphiles do not interact with bacterial DNA, they were subjected to synergy evaluation for combinations with conventional antibiotics. Synergy was observed for combinations with tetracycline against sensitive S. aureus and E. coli, as well as with ciprofloxacin and colistin against resistant strains. Additivity with a remarkable recovery in activity of conventional antibiotics (from 2-fold to \u226532-fold) together with largely subtoxic concentrations of \u03b1-hydrazido acid derivatives was found for combinations with ciprofloxacin toward susceptible S. aureus and methicillin toward MRSa. However, no potentiation of conventional antibiotics was observed for combinations with linezolid and gentamicin against the corresponding resistant S. aureus and E. coli strains.<\/jats:p>","DOI":"10.3390\/molecules29174078","type":"journal-article","created":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T11:54:10Z","timestamp":1724846050000},"page":"4078","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Investigation on the Synergy between Membrane Permeabilizing Amphiphilic \u03b1-Hydrazido Acids and Commonly Used Antibiotics against Drug-Resistant Bacteria"],"prefix":"10.3390","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8034-8557","authenticated-orcid":false,"given":"Cristina","family":"Minnelli","sequence":"first","affiliation":[{"name":"Department of Life and Environmental Sciences, Polytechnic University of Marche, Via Brecce Bianche, 60131 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5035-5879","authenticated-orcid":false,"given":"Gianmarco","family":"Mangiaterra","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Science, University of Urbino \u201cCarlo Bo\u201d, 61032 Urbino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8053-6539","authenticated-orcid":false,"given":"Emiliano","family":"Laudadio","sequence":"additional","affiliation":[{"name":"Department of Science and Engineering of Matter, Environment and Urban Planning, Polytechnic University of Marche, Via Brecce Bianche, 60131 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3346-6379","authenticated-orcid":false,"given":"Barbara","family":"Citterio","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Science, University of Urbino \u201cCarlo Bo\u201d, 61032 Urbino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9035-1044","authenticated-orcid":false,"given":"Samuele","family":"Rinaldi","sequence":"additional","affiliation":[{"name":"Department of Life and Environmental Sciences, Polytechnic University of Marche, Via Brecce Bianche, 60131 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,28]]},"reference":[{"key":"ref_1","unstructured":"(2024, March 27). See, for Example. Available online: https:\/\/www.who.int\/antimicrobial-resistance\/en\/."},{"key":"ref_2","unstructured":"(2024, March 25). No Time to Wait: Securing the Future from Drug-Resistant Infections. Available online: https:\/\/www.who.int\/publications\/i\/item\/no-time-to-wait-securing-the-future-from-drug-resistant-infections."},{"key":"ref_3","unstructured":"O\u2019Neill, J. (2024, March 28). Tackling Drug-Resistant Infections Globally: Final Report and Recommendations. Review on Antimicrobial Resistance 2016. Wellcome Trust and HM Government. Available online: https:\/\/amr-review.org\/sites\/default\/files\/160525_Final%20paper_with%20cover.pdf."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1016\/S1473-3099(16)30127-X","article-title":"Reflecting on the final report of the O\u2019Neill Review on Antimicrobial Resistance","volume":"16","author":"Piddock","year":"2016","journal-title":"Lancet Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/nrd3591","article-title":"Designing antimicrobial peptides: Form follows function","volume":"11","author":"Fjell","year":"2012","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1038\/nrmicro1098","article-title":"Antimicrobial peptides: Pore formers or metabolic inhibitors in bacteria?","volume":"3","author":"Brogden","year":"2005","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1002\/psc.704","article-title":"Function and therapeutic potential of host defense peptides","volume":"11","author":"McPhee","year":"2005","journal-title":"J. Pept. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"R27","DOI":"10.1186\/cc3995","article-title":"Toxicity of polymyxins: A systematic review of the evidence from old and recent studies","volume":"10","author":"Falagas","year":"2006","journal-title":"Crit. Care"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1038\/nbt1267","article-title":"Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies","volume":"24","author":"Hancock","year":"2006","journal-title":"Nat. Biotechnol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"44420","DOI":"10.1021\/acsami.0c09931","article-title":"Aggregated Amphiphilic Antimicrobial Peptides Embedded in Bacterial Membranes","volume":"12","author":"Gong","year":"2020","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Hollmann, A., Martinez, M., Maturana, P., Semorile, L.C., and Maffia, P.C. (2018). Antimicrobial peptides: Interaction with model and biological membranes and synergism with chemical antibiotics. Front. Chem., 6.","DOI":"10.3389\/fchem.2018.00204"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"101829","DOI":"10.1016\/j.cocis.2024.101829","article-title":"Combinatorial therapies of surfactant-like antimicrobial peptides and antibiotics for improved therapeutic efficacy","volume":"73","author":"Liao","year":"2024","journal-title":"Curr. Opin. Colloid Interface Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1038\/nchembio.559","article-title":"Combinations of antibiotics and nonantibiotic drugs enhance antimicrobial efficacy","volume":"7","author":"Ejim","year":"2011","journal-title":"Nat. Chem. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Molchanova, N., Hansen, P.R., and Franzyk, H. (2017). Advances in development of antimicrobial peptidomimetics as potential drugs. Molecules, 22.","DOI":"10.3390\/molecules22091430"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"12774","DOI":"10.1021\/ja0270423","article-title":"Structure-Activity studies of 14-helical antimicrobial \u03b2-peptides: Probing the relationship between conformational stability and antimicrobial potency","volume":"124","author":"Raguse","year":"2002","journal-title":"J. Am. Chem. Soc."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1128\/AAC.01080-10","article-title":"Short alkylated peptoid mimics of antimicrobial lipopeptides","volume":"55","author":"Chongsiriwatana","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.chembiol.2006.03.009","article-title":"Mimicking Helical Antibacterial Peptides with Nonpeptidic Folding Oligomers","volume":"13","author":"Violette","year":"2006","journal-title":"Chem. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5786","DOI":"10.1021\/jm200450h","article-title":"A synthetic antimicrobial peptidomimetic (LTX 109): Stereochemical impact on membrane disruption","volume":"54","author":"Isaksson","year":"2011","journal-title":"J. Med. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"6968","DOI":"10.1073\/pnas.0811818106","article-title":"De novo design and in vivo activity of conformationally restrained antimicrobial arylamide foldamers","volume":"106","author":"Choi","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1021\/ml300307b","article-title":"Role of amphiphilicity in the design of synthetic mimics of antimicrobial peptides with gram-negative activity","volume":"4","author":"Thaker","year":"2013","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2500","DOI":"10.1016\/j.bbamem.2007.05.023","article-title":"Bacterial lipid composition and the antimicrobial efficacy of cationic steroid compounds (Ceragenins)","volume":"1768","author":"Epand","year":"2007","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"11395","DOI":"10.1021\/acs.jmedchem.1c00734","article-title":"Amphipathic Barbiturates as Mimics of Antimicrobial Peptides and the Marine Natural Products Eusynstyelamides with Activity against Multi-resistant Clinical Isolates","volume":"64","author":"Paulsen","year":"2021","journal-title":"J. Med. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"12225","DOI":"10.1021\/la302303d","article-title":"Cleavable cationic antibacterial amphiphiles: Synthesis, mechanism of action, and cytotoxicities","volume":"28","author":"Hoque","year":"2012","journal-title":"Langmuir"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1021\/jm901052r","article-title":"Antimicrobial activity of small \u03b2-peptidomimetics based on the pharmacophore model of short cationic antimicrobial peptides","volume":"53","author":"Hansen","year":"2010","journal-title":"J. Med. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1002\/anie.200904392","article-title":"Binaphthyl-based dicationic peptoids with therapeutic potential","volume":"49","author":"Bremner","year":"2010","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"9729","DOI":"10.1039\/c1cc13684d","article-title":"Non-hemolytic \u03b1-AApeptides as antimicrobial peptidomimetics","volume":"47","author":"Padhee","year":"2011","journal-title":"Chem. Commun."},{"key":"ref_27","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_28","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.1021\/jm401680a","article-title":"Small molecular antibacterial peptoid mimics: The simpler the better!","volume":"57","author":"Ghosh","year":"2014","journal-title":"J. Med. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1021\/acs.biomac.1c01528","article-title":"Polymeric Biomaterials for Prevention and Therapeutic Intervention of Microbial Infections","volume":"23","author":"Ghosh","year":"2022","journal-title":"Biomacromolecules"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1002\/ejoc.201801427","article-title":"Imidazolidinone-Tethered \u03b1-Hydrazidopeptides\u2013Synthesis and Conformational Investigation","volume":"2019","author":"Amabili","year":"2019","journal-title":"Eur. J. Org. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"112072","DOI":"10.1016\/j.ejmech.2020.112072","article-title":"Simple amphiphilic \u03b1-hydrazido acids: Rational design, synthesis, and in vitro bioactivity profile of a novel class of potential antimicrobial compounds","volume":"189","author":"Amabili","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1128\/CMR.00064-16","article-title":"Polymyxins: Antibacterial activity, susceptibility testing, and resistance mechanisms encoded by plasmids or chromosomes","volume":"30","author":"Poirel","year":"2017","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4242","DOI":"10.1021\/acsami.5b12688","article-title":"Selective Antimicrobial Activities and Action Mechanism of Micelles Self-Assembled by Cationic Oligomeric Surfactants","volume":"8","author":"Zhou","year":"2016","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/S1473-3099(15)00424-7","article-title":"Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: A microbiological and molecular biological study","volume":"16","author":"Liu","year":"2016","journal-title":"Lancet Infect. Dis."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Berglund, N.A., Piggot, T.J., Jefferies, D., Sessions, R.B., Bond, P.J., and Khalid, S. (2015). Interaction of the Antimicrobial Peptide Polymyxin B1 with Both Membranes of E. coli: A Molecular Dynamics Study. PLoS Comput. Biol., 11.","DOI":"10.1371\/journal.pcbi.1004180"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"E7587","DOI":"10.1073\/pnas.1803975115","article-title":"Liquid crystalline bacterial outer membranes are critical for antibiotic susceptibility","volume":"115","author":"Paracini","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.bbamem.2005.08.007","article-title":"Lysolipid incorporation in dipalmitoylphosphatidylcholine bilayer membranes enhances the ion permeability and drug release rates at the membrane phase transition","volume":"1716","author":"Mills","year":"2005","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.chemphyslip.2014.10.004","article-title":"Cholesterol, sphingolipids, and glycolipids: What do we know about their role in raft-like membranes?","volume":"184","author":"Vattulainen","year":"2014","journal-title":"Chem. Phys. Lipids"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2254","DOI":"10.1016\/j.bbamem.2016.03.032","article-title":"Permeability across lipid membranes","volume":"1858","author":"Shinoda","year":"2016","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1002\/jlb.60.1.8","article-title":"Endotoxin signal transduction in macrophages","volume":"60","author":"Sweet","year":"1996","journal-title":"J. Leukoc. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/S0140-6736(97)80051-7","article-title":"Peptide antibiotics","volume":"349","author":"Hancock","year":"1997","journal-title":"Lancet"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2378","DOI":"10.1128\/AAC.06107-11","article-title":"Antimicrobial action and cell agglutination by the eosinophil cationic protein are modulated by the cell wall lipopolysaccharide structure","volume":"56","author":"Pulido","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.2174\/1568026043388079","article-title":"Endotoxin Neutralizing Peptides","volume":"4","author":"Jerala","year":"2004","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3080","DOI":"10.2174\/092986710791959756","article-title":"De novo Designed Lipopolysaccharide Binding Peptides: Structure Based Development of Antiendotoxic and Antimicrobial Drugs","volume":"17","author":"Bhattacharjya","year":"2010","journal-title":"Curr. Med. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3544","DOI":"10.1021\/bi702065b","article-title":"Eosinophil cationic protein high-affinity binding to bacteria-wall lipopolysaccharides and peptidoglycans","volume":"47","author":"Torrent","year":"2008","journal-title":"Biochemistry"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1006\/bbrc.1998.8159","article-title":"Mechanism of Action of the Antimicrobial Peptide Buforin II: Buforin II Kills Microorganisms by Penetrating the Cell Membrane and Inhibiting Cellular Functions","volume":"244","author":"Park","year":"1998","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.ijantimicag.2012.04.014","article-title":"Expression of multidrug resistance efflux pump genes in clinical and environmental isolates of Staphylococcus aureus","volume":"40","author":"Kosmidis","year":"2012","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1080\/14756366.2020.1719083","article-title":"C-2 phenyl replacements to obtain potent quinoline-based Staphylococcus aureus NorA inhibitors","volume":"35","author":"Felicetti","year":"2020","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/jac\/dkg301","article-title":"Synergy, antagonism, and what the chequerboard puts between them","volume":"52","author":"Odds","year":"2003","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"European Committee for Antimicrobial Susceptibility Testing (EUCAST) of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) (2000). Terminology relating to methods for the determination of susceptibility of bacteria to antimicrobial agents. Clin. Microbiol. Infect., 6, 503\u2013508.","DOI":"10.1046\/j.1469-0691.2000.00149.x"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1128\/AAC.00999-09","article-title":"Defining fractional inhibitory concentration index cutoffs for additive interactions based on self-drug additive combinations, Monte Carlo simulation analysis, and in vitro-in vivo correlation data for antifungal drug combinations against Aspergillus fumigatus","volume":"54","author":"Meletiadis","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.resmic.2012.06.001","article-title":"Synergistic effect of antimicrobial peptide arenicin-1 in combination with antibiotics against pathogenic bacteria","volume":"163","author":"Choi","year":"2012","journal-title":"Res. Microbiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.micres.2016.11.005","article-title":"A novel interpretation of the Fractional Inhibitory Concentration Index: The case Origanum vulgare L. and Leptospermum scoparium J. R. et G. Forst essential oils against Staphylococcus aureus strains","volume":"195","author":"Fratini","year":"2017","journal-title":"Microbiol. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1016\/j.bbapap.2008.11.005","article-title":"Outer membrane permeability and antibiotic resistance","volume":"1794","author":"Delcour","year":"2009","journal-title":"Biochim. Biophys. Acta-Proteins Proteom."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"5399","DOI":"10.1128\/AAC.00578-11","article-title":"Functional synergy between antimicrobial peptoids and peptides against gram-negative bacteria","volume":"55","author":"Chongsiriwatana","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"4433","DOI":"10.1128\/AAC.00594-16","article-title":"rRNA binding sites and the molecular mechanism of action of the tetracyclines","volume":"60","author":"Chukwudi","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2349","DOI":"10.1093\/jac\/dkw108","article-title":"Linezolid-resistant cfr-positive MRSA, Italy","volume":"71","author":"Antonelli","year":"2016","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Shaheen, A., Tariq, A., Iqbal, M., Mirza, O., Haque, A., Walz, T., and Rahman, M. (2021). Mutational Diversity in the Quinolone Resistance-Determining Regions of Type-II Topoisomerases of Salmonella Serovars. Antibiotics, 10.","DOI":"10.3390\/antibiotics10121455"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.1039\/C9MD00120D","article-title":"Quinolone antibiotics","volume":"10","author":"Pham","year":"2019","journal-title":"MedChemComm"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.diagmicrobio.2017.12.015","article-title":"Spread of colistin resistance gene mcr-1 in Italy: Characterization of the mcr-1.2 allelic variant in a colistin-resistant blood isolate of Escherichia coli","volume":"91","author":"Simoni","year":"2018","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.diagmicrobio.2018.10.023","article-title":"In vitro activity of Plazomicin against Enterobacteriaceae isolates carrying genes encoding aminoglycoside-modifying enzymes most common in US Census divisions","volume":"94","author":"Castanheira","year":"2019","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1097\/SHK.0000000000000584","article-title":"Enhanced efficacy of combinations of pexiganan with colistin versus Acinetobacter baumannii in experimental sepsis","volume":"46","author":"Cirioni","year":"2016","journal-title":"Shock"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1007\/s00430-019-00624-7","article-title":"In vitro activity of Protegrin-1, alone and in combination with clinically useful antibiotics, against Acinetobacter baumannii strains isolated from surgical wounds","volume":"208","author":"Morroni","year":"2019","journal-title":"Med. Microbiol. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.1128\/IAI.67.4.2005-2009.1999","article-title":"Biological Properties of Structurally Related-Helical Cationic Antimicrobial Peptides","volume":"67","author":"Scott","year":"1999","journal-title":"Infect. Immun."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"939","DOI":"10.2147\/DDDT.S107195","article-title":"Synergistic effects of antimicrobial peptide DP7 combined with antibiotics against multidrug-resistant bacteria","volume":"11","author":"Wu","year":"2017","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Arenas, I., Villegas, E., Walls, O., Barrios, H., Rodr\u00edguez, R., Corzo, G., and Rutledge, P.J. (2016). Antimicrobial activity and stability of short and long based arachnid synthetic peptides in the presence of commercial antibiotics. Molecules, 21.","DOI":"10.3390\/molecules21020225"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Kampshoff, F., Willcox, M.D.P., and Dutta, D. (2019). A pilot study of the synergy between two antimicrobial peptides and two common antibiotics. Antibiotics, 8.","DOI":"10.3390\/antibiotics8020060"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"6233","DOI":"10.1128\/AAC.01245-15","article-title":"Antimicrobial peptide novicidin synergizes with rifampin, ceftriaxone, and ceftazidime against antibiotic-resistant Enterobacteriaceae in vitro","volume":"59","author":"Soren","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2478","DOI":"10.1128\/AAC.01553-05","article-title":"Interaction of antimicrobial peptide temporin L with lipopolysaccharide in vitro and in experimental rat models of septic shock caused by gram-negative bacterial","volume":"50","author":"Giacometti","year":"2006","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"5647","DOI":"10.1111\/j.1742-4658.2009.07257.x","article-title":"Esculentin-1b(1-18)\u2014A membrane-active antimicrobial peptide that synergizes with antibiotics and modifies the expression level of a limited number of proteins in Escherichia coli","volume":"276","author":"Marcellini","year":"2009","journal-title":"FEBS J."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Mohamed, M.F., Abdelkhalek, A., and Seleem, M.N. (2016). Evaluation of short synthetic antimicrobial peptides for treatment of drug-resistant and intracellular Staphylococcus aureus. Sci. Rep., 6.","DOI":"10.1038\/srep29707"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"S48","DOI":"10.1093\/cid\/civ523","article-title":"Evolving Resistance among Gram-positive Pathogens","volume":"61","author":"Munita","year":"2015","journal-title":"Clin. Inf. Dis."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1002\/iub.1289","article-title":"Penicillin-binding protein 2a of methicillin-resistant Staphylococcus aureus","volume":"66","author":"Fishovitz","year":"2014","journal-title":"IUBMB Life"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"6","DOI":"10.15379\/2410-3802.2017.03.02","article-title":"Combinational Synergy of Antibiotics and Antimicrobial Peptides","volume":"3","author":"Shah","year":"2017","journal-title":"J. Transl. Proteomics Res."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Duong, L., Gross, S.P., and Siryaporn, A. (2021). Developing Antimicrobial Synergy with AMPs. Front. Med. Technol., 3.","DOI":"10.3389\/fmedt.2021.640981"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1093\/jac\/dkq106","article-title":"Evaluation of synergistic activity of bovine lactoferricin with antibiotics in corneal infection","volume":"65","author":"Oo","year":"2010","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1128\/AAC.05702-11","article-title":"Resistance to linezolid caused by modifications at its binding site on the ribosome","volume":"56","author":"Long","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_78","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_79","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1093\/jac\/dkp309","article-title":"Decreased linezolid uptake in an in vitro-selected linezolid-resistant Staphylococcus epidermidis mutant","volume":"64","author":"Sierra","year":"2009","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1128\/AAC.31.2.230","article-title":"Decreased Binding of Antibiotics to Lipopolysaccharides from Polymyxin-Resistant Strains of Escherichia coli and Salmonella typhimurium","volume":"31","author":"Peterson","year":"1987","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_81","unstructured":"Frisch, M.J., Trucks, G.W., Schlegel, H.B., Scuseria, G.E., Robb, M.A., Cheeseman, J.R., Scalmani, G., Barone, V., Petersson, G.A., and Nakatsuji, H. (2016). Gaussian 16, Revision B.01, Gaussian, Inc."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"084106","DOI":"10.1063\/1.2834918","article-title":"Systematic optimization of long-range corrected hybrid density functionals","volume":"128","year":"2008","journal-title":"J. Chem. Phys."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1021\/ct300715s","article-title":"Long-range corrected hybrid density functionals with improved dispersion corrections","volume":"9","author":"Lin","year":"2013","journal-title":"J. Chem. Theory Comput."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2999","DOI":"10.1021\/cr9904009","article-title":"Quantum mechanical continuum solvation models","volume":"105","author":"Tomasi","year":"2005","journal-title":"Chem. Rev."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Park, S.J., Kern, N., Brown, T., Lee, J., and Im, W. (2023). CHARMM-GUI PDB Manipulator: Various PDB Structural Modifications for Biomolecular Modeling and Simulation. J. Mol. Biol., 435.","DOI":"10.1016\/j.jmb.2023.167995"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1016\/j.bbamem.2012.01.009","article-title":"Membrane models of E. coli containing cyclic moieties in the aliphatic lipid chain","volume":"1818","author":"Pandit","year":"2012","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"9954","DOI":"10.1021\/jp003020w","article-title":"Structure and dynamics of the TIP3P, SPC, and SPC\/E water models at 298 K","volume":"105","author":"Mark","year":"2001","journal-title":"J. Phys. Chem. A"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1002\/jcc.20291","article-title":"GROMACS: Fast, flexible, and free","volume":"26","author":"Lindahl","year":"2005","journal-title":"J. Comput. Chem."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.softx.2015.06.001","article-title":"Gromacs: High performance molecular simulations through multi-level parallelism from laptops to supercomputers","volume":"1\u20132","author":"Abraham","year":"2015","journal-title":"SoftwareX"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2641","DOI":"10.1016\/j.cpc.2013.06.003","article-title":"A flexible algorithm for calculating pair interactions on SIMD architectures","volume":"184","author":"Hess","year":"2013","journal-title":"Comput. Phys. Commun."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"10089","DOI":"10.1063\/1.464397","article-title":"Particle mesh Ewald: An N\u00b7log(N) method for Ewald sums in large systems","volume":"98","author":"Darden","year":"1993","journal-title":"J. Chem. Phys."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1063\/1.447334","article-title":"A unified formulation of the constant temperature molecular dynamics methods","volume":"81","year":"1984","journal-title":"J. Chem. Phys."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"7182","DOI":"10.1063\/1.328693","article-title":"Polymorphic transitions in single crystals: A new molecular dynamics method","volume":"52","author":"Parrinello","year":"1981","journal-title":"J. Appl. Phys."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0263-7855(96)00018-5","article-title":"VMD: Visual Molecular Dynamics","volume":"14","author":"Humphrey","year":"1997","journal-title":"J. Mol. Graph."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera\u2014A visualization system for exploratory research and analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J. Comput. Chem."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1042\/BJ20080543","article-title":"Growth of \u03b22-microglobulin-related amyloid fibrils by non-esterified fatty acids at a neutral pH","volume":"416","author":"Hasegawa","year":"2008","journal-title":"Biochem. J."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"5059","DOI":"10.1007\/s00253-016-7400-4","article-title":"Antimicrobial peptide melittin against Xanthomonas oryzae pv. oryzae, the bacterial leaf blight pathogen in rice","volume":"100","author":"Shi","year":"2016","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"239","DOI":"10.2174\/1386207043328832","article-title":"Anti-Endotoxin Agents. 1. Development of a Fluorescent Probe Displacement Method Optimized for High-Throughput Identification of Lipopolysaccharide-Binding Agents","volume":"7","author":"Wood","year":"2004","journal-title":"Comb. Chem. High Throughput Screen."},{"key":"ref_99","unstructured":"Patel, J.B., Cockerill, F.R., Bradford, P.A., Eliopoulos, G.M., Hindler, J.A., Jenkins, S.G., Lewis, J.S., Limbago, B., Miller, L.A., and Nicolau, D.P. (2017). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically, Clinical and Laboratory Standards Institute. Approved Standard-Tenth Edition (2017) Document M07-A10, Volume 35, No 2."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/29\/17\/4078\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:44:23Z","timestamp":1760111063000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/29\/17\/4078"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,28]]},"references-count":99,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["molecules29174078"],"URL":"https:\/\/doi.org\/10.3390\/molecules29174078","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,28]]}}}