{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T01:27:54Z","timestamp":1782437274781,"version":"3.54.5"},"reference-count":74,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2021,8,13]],"date-time":"2021-08-13T00:00:00Z","timestamp":1628812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondation pour la Recherche M\u00e9dicale, SATT Linksium Grenoble Alpes and Labex Arcane; CBH-EUR-GS","award":["DBF20161136768 ANR-17-EURE-0003"],"award-info":[{"award-number":["DBF20161136768 ANR-17-EURE-0003"]}]},{"name":"Fonds de la Recherche Scientifique Medicale","award":["T.1003.14 and J.0205.16"],"award-info":[{"award-number":["T.1003.14 and J.0205.16"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Development of novel therapeutics to treat antibiotic-resistant infections, especially those caused by ESKAPE pathogens, is urgent. One of the most critical pathogens is P. aeruginosa, which is able to develop a large number of factors associated with antibiotic resistance, including high level of impermeability. Gram-negative bacteria are protected from the environment by an asymmetric Outer Membrane primarily composed of lipopolysaccharides (LPS) at the outer leaflet and phospholipids in the inner leaflet. Based on a large hemi-synthesis program focusing on amphiphilic aminoglycoside derivatives, we extend the antimicrobial activity of 3\u2032,6-dinonyl neamine and its branched isomer, 3\u2032,6-di(dimethyloctyl) neamine on clinical P. aeruginosa, ESBL, and carbapenemase strains. We also investigated the capacity of 3\u2032,6-homodialkyl neamine derivatives carrying different alkyl chains (C7\u2013C11) to interact with LPS and alter membrane permeability. 3\u2032,6-Dinonyl neamine and its branched isomer, 3\u2032,6-di(dimethyloctyl) neamine showed low MICs on clinical P. aeruginosa, ESBL, and carbapenemase strains with no MIC increase for long-duration incubation. In contrast from what was observed for membrane permeability, length of alkyl chains was critical for the capacity of 3\u2032,6-homodialkyl neamine derivatives to bind to LPS. We demonstrated the high antibacterial potential of the amphiphilic neamine derivatives in the fight against ESKAPE pathogens and pointed out some particular characteristics making the 3\u2032,6-dinonyl- and 3\u2032,6-di(dimethyloctyl)-neamine derivatives the best candidates for further development.<\/jats:p>","DOI":"10.3390\/ijms22168707","type":"journal-article","created":{"date-parts":[[2021,8,13]],"date-time":"2021-08-13T09:22:38Z","timestamp":1628846558000},"page":"8707","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Interest of Homodialkyl Neamine Derivatives against Resistant P. aeruginosa, E. coli, and \u03b2-Lactamases-Producing Bacteria\u2014Effect of Alkyl Chain Length on the Interaction with LPS"],"prefix":"10.3390","volume":"22","author":[{"given":"Jitendriya","family":"Swain","sequence":"first","affiliation":[{"name":"Universit\u00e9 Catholique de Louvain, Louvain Drug Research Institute, Pharmacologie Cellulaire et Mol\u00e9culaire, Avenue E. Mounier 73, UCL B1.73.05, 1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cl\u00e9ment","family":"Dezanet","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Grenoble Alpes, CNRS, D\u00e9partement de Pharmacochimie Mol\u00e9culaire, Rue de la Chimie, F-38041 Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hussein","family":"Chalhoub","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Catholique de Louvain, Louvain Drug Research Institute, Pharmacologie Cellulaire et Mol\u00e9culaire, Avenue E. Mounier 73, UCL B1.73.05, 1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Auqui\u00e8re","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Catholique de Louvain, Louvain Drug Research Institute, Pharmacologie Cellulaire et Mol\u00e9culaire, Avenue E. Mounier 73, UCL B1.73.05, 1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Kempf","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Grenoble Alpes, CNRS, D\u00e9partement de Pharmacochimie Mol\u00e9culaire, Rue de la Chimie, F-38041 Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7058-1304","authenticated-orcid":false,"given":"Jean-Luc","family":"D\u00e9cout","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Grenoble Alpes, CNRS, D\u00e9partement de Pharmacochimie Mol\u00e9culaire, Rue de la Chimie, F-38041 Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Paule","family":"Mingeot-Leclercq","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Catholique de Louvain, Louvain Drug Research Institute, Pharmacologie Cellulaire et Mol\u00e9culaire, Avenue E. Mounier 73, UCL B1.73.05, 1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S7","DOI":"10.1086\/655995","article-title":"Progress and Challenges in Implementing the Research on ESKAPE Pathogens","volume":"31","author":"Rice","year":"2010","journal-title":"Infect. Control Hosp. Epidemiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"539","DOI":"10.3389\/fmicb.2019.00539","article-title":"Emerging Strategies to Combat ESKAPE Pathogens in the Era of Antimicrobial Resistance: A Review","volume":"10","author":"Mulani","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13756-019-0590-7","article-title":"Economic burden of antibiotic resistance in ESKAPE organisms: A systematic review","volume":"8","author":"Zhen","year":"2019","journal-title":"Antimicrob. Resist. Infect. Control"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2475067","DOI":"10.1155\/2016\/2475067","article-title":"Mechanisms of Antimicrobial Resistance in ESKAPE Pathogens","volume":"2016","author":"Santajit","year":"2016","journal-title":"BioMed Res. Int."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.gendis.2019.04.001","article-title":"Emergence of antibiotic resistance Pseudomonas aeruginosa in intensive care unit; a critical review","volume":"6","author":"Pachori","year":"2019","journal-title":"Genes Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"421","DOI":"10.3389\/fmicb.2015.00421","article-title":"Recent advances toward a molecular mechanism of efflux pump inhibition","volume":"6","author":"Opperman","year":"2015","journal-title":"Front. Microbiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"57","DOI":"10.3389\/fmolb.2018.00057","article-title":"Functional Mechanism of the Efflux Pumps Transcription Regulators from Pseudomonas aeruginosa Based on 3D Structures","volume":"5","author":"Housseini","year":"2018","journal-title":"Front. Mol. Biosci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1007\/s10096-018-3244-4","article-title":"Molecular epidemiology of carbapenem-resistant Pseudomonas aeruginosa in an endemic area: Comparison with global data","volume":"37","author":"Karampatakis","year":"2018","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1126\/science.274.5291.1367","article-title":"Structure of the A Site of Escherichia coli 16S Ribosomal RNA Complexed with an Aminoglycoside Antibiotic","volume":"274","author":"Fourmy","year":"1996","journal-title":"Science"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1006\/jmbi.1997.1552","article-title":"Binding of neomycin-class aminoglycoside antibiotics to the A-site of 16 s rRNA","volume":"277","author":"Fourmy","year":"1998","journal-title":"J. Mol. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1006\/jmbi.1997.1551","article-title":"Paromomycin binding induces a local conformational change in the A-site of 16 s rRNA","volume":"277","author":"Fourmy","year":"1998","journal-title":"J. Mol. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1128\/AAC.43.4.727","article-title":"Aminoglycosides: Activity and Resistance","volume":"43","author":"Glupczynski","year":"1999","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1682","DOI":"10.1016\/j.febslet.2011.04.054","article-title":"Strategies for bypassing the membrane barrier in multidrug resistant Gram-negative bacteria","volume":"585","author":"Bolla","year":"2011","journal-title":"FEBS Lett."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1007\/BF01975036","article-title":"Antibiotic uptake into gram-negative bacteria","volume":"7","author":"Hancock","year":"1988","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e00077-17","DOI":"10.1128\/CMR.00077-17","article-title":"Antibiotic Hybrids: The Next Generation of Agents and Adjuvants against Gram-Negative Pathogens?","volume":"31","author":"Domalaon","year":"2018","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"8786","DOI":"10.1021\/nn502201a","article-title":"Engineering Persister-Specific Antibiotics with Synergistic Antimicrobial Functions","volume":"8","author":"Schmidt","year":"2014","journal-title":"ACS Nano"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Dezanet, C., Kempf, J., Mingeot-Leclercq, M.-P., and D\u00e9cout, J.-L. (2020). Amphiphilic Aminoglycosides as Medicinal Agents. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21197411"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1021\/acsinfecdis.8b00036","article-title":"Molecular Properties That Define the Activities of Antibiotics in Escherichia coli and Pseudomonas aeruginosa","volume":"4","author":"Cooper","year":"2018","journal-title":"ACS Infect. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"7691","DOI":"10.1021\/jm401148j","article-title":"Tuning the Antibacterial Activity of Amphiphilic Neamine Derivatives and Comparison to Paromamine Homologues","volume":"56","author":"Zimmermann","year":"2013","journal-title":"J. Med. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"9350","DOI":"10.1021\/acs.jmedchem.6b00818","article-title":"New Broad-Spectrum Antibacterial Amphiphilic Aminoglycosides Active against Resistant Bacteria: From Neamine Derivatives to Smaller Neosamine Analogues","volume":"59","author":"Zimmermann","year":"2016","journal-title":"J. Med. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1016\/j.ejmech.2018.08.022","article-title":"Broad-spectrum antibacterial amphiphilic aminoglycosides: A new focus on the structure of the lipophilic groups extends the series of active dialkyl neamines","volume":"157","author":"Zimmermann","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1021\/jm900615h","article-title":"Synthesis and antimicrobial evaluation of amphiphilic neamine derivatives","volume":"53","author":"Baussanne","year":"2010","journal-title":"J. Med. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4420","DOI":"10.1128\/AAC.02536-13","article-title":"New amphiphilic neamine derivatives active against resistant Pseudomonas aeruginosa and their interactions with lipopolysaccharides","volume":"58","author":"Sautrey","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_24","first-page":"1","article-title":"Targeting Bacterial Cardiolipin Enriched Microdomains: An Antimicrobial Strategy Used by Amphiphilic Aminoglycoside Antibiotics","volume":"7","author":"Swain","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"239","DOI":"10.2174\/1386207043328832","article-title":"Anti-Endotoxin Agents. Development of a Fluorescent Probe Displacement Method Optimized for the Rapid Identification of Lipopolysaccharide-Binding Agents. 1","volume":"7","author":"Wood","year":"2004","journal-title":"Comb. Chem. High Throughput Screen."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"733","DOI":"10.2174\/1386207043328229","article-title":"Anti-endotoxin agents. 2. Pilot high-throughput screening for novel lipopolysaccharide-recognizing motifs in small molecules","volume":"7","author":"Wood","year":"2004","journal-title":"Comb. Chem. High Throughput Screen."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1046\/j.1365-2672.1997.00316.x","article-title":"Cell membrane integrity and lysis in Lactococcus lactis: The detection of a population of permeable cells in post-logarithmic phase cultures","volume":"84","author":"Niven","year":"1998","journal-title":"J. Appl. Microbiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1093\/jac\/dks121","article-title":"OXA-48-like carbapenemases: The phantom menace","volume":"67","author":"Poirel","year":"2012","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1716","DOI":"10.1016\/j.bbamem.2011.01.014","article-title":"The Pseudomonas aeruginosa membranes: A target for a new amphiphilic aminoglycoside derivative?","volume":"1808","author":"Ouberai","year":"2011","journal-title":"Biochim. Biophys. Acta BBA Biomembr."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1002\/bip.22095","article-title":"Biophysical characterization of polymyxin b interaction with LPS aggregates and membrane model systems","volume":"98","author":"Domingues","year":"2012","journal-title":"Biopolymers"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"6970","DOI":"10.1021\/la048218c","article-title":"Probing the Properties of Lipopolysaccharide Monolayers and Their Interaction with the Antimicrobial Peptide Polymyxin B by Atomic Force Microscopy","volume":"21","author":"Roes","year":"2005","journal-title":"Langmuir"},{"key":"ref_32","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_33","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1038\/d41586-019-03730-x","article-title":"New antibiotics target the outer membrane of bacteria","volume":"576","author":"Sousa","year":"2019","journal-title":"Nature"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"45","DOI":"10.3389\/fchem.2019.00045","article-title":"Folded Synthetic Peptides and Other Molecules Targeting Outer Membrane Protein Complexes in Gram-Negative Bacteria","volume":"7","author":"Robinson","year":"2019","journal-title":"Front. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Lehman, K.M., and Grabowicz, M. (2019). Countering Gram-Negative Antibiotic Resistance: Recent Progress in Disrupting the Outer Membrane with Novel Therapeutics. Antibiotics, 8.","DOI":"10.3390\/antibiotics8040163"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Fosso, M.Y., Shrestha, S.K., Chandrika, N.T., Dennis, E.K., Green, K.D., and Garneau-Tsodikova, S. (2018). Differential Effects of Linkers on the Activity of Amphiphilic Tobramycin Antifungals. Molecules, 23.","DOI":"10.3390\/molecules23040899"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1021\/acsinfecdis.7b00272","article-title":"Increased Degree of Unsaturation in the Lipid of Antifungal Cationic Amphiphiles Facilitates Selective Fungal Cell Disruption","volume":"4","author":"Steinbuch","year":"2018","journal-title":"ACS Infect. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4861","DOI":"10.1128\/AAC.00229-15","article-title":"Amphiphilic Tobramycin Analogues as Antibacterial and Antifungal Agents","volume":"59","author":"Shrestha","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3684","DOI":"10.1021\/acs.jmedchem.6b01742","article-title":"Amphiphilic Tobramycin\u2013Lysine Conjugates Sensitize Multidrug Resistant Gram-Negative Bacteria to Rifampicin and Minocycline","volume":"60","author":"Lyu","year":"2017","journal-title":"J. Med. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1038\/ja.2012.59","article-title":"Antibacterial activity of amphiphilic tobramycin","volume":"65","author":"Dhondikubeer","year":"2012","journal-title":"J. Antibiot."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4340","DOI":"10.1002\/chem.201406404","article-title":"Tobramycin and Nebramine as Pseudo-oligosaccharide Scaffolds for the Development of Antimicrobial Cationic Amphiphiles","volume":"21","author":"Herzog","year":"2015","journal-title":"Chem. A Eur. J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.ejmech.2019.05.003","article-title":"Amphiphilic nebramine-based hybrids Rescue legacy antibiotics from intrinsic resistance in multidrug-resistant Gram-negative bacilli","volume":"175","author":"Yang","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1039\/C5MD00503E","article-title":"Bacterial lipid membranes as promising targets to fight antimicrobial resistance, molecular foundations and illustration through the renewal of aminoglycoside antibiotics and emergence of amphiphilic aminoglycosides","volume":"7","year":"2016","journal-title":"MedChemComm"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e02256-16","DOI":"10.1128\/AAC.02256-16","article-title":"Pseudomonas aeruginosa Oligoribonuclease Contributes to Tolerance to Ciprofloxacin by Regulating Pyocin Biosynthesis","volume":"61","author":"Chen","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1762","DOI":"10.3389\/fmicb.2019.01762","article-title":"Pseudomonas aeruginosa Polynucleotide Phosphorylase Contributes to Ciprofloxacin Resistance by Regulating PrtR","volume":"10","author":"Fan","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1128\/AAC.26.1.48","article-title":"Compounds which increase the permeability of the Pseudomonas aeruginosa outer membrane","volume":"26","author":"Hancock","year":"1984","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"7071","DOI":"10.1073\/pnas.0509392103","article-title":"Crystal structure and catalytic mechanism of the LPS 3-O-deacylase PagL from Pseudomonas aeruginosa","volume":"103","author":"Rutten","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1038\/s41579-019-0201-x","article-title":"Pushing the envelope: LPS modifications and their consequences","volume":"17","author":"Simpson","year":"2019","journal-title":"Nat. Rev. Genet."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/S0009-3084(97)00093-5","article-title":"Characterization of the nonlamellar cubic and HII structures of lipid A from Salmonella enterica serovar Minnesota by X-ray diffraction and freeze-fracture electron microscopy","volume":"91","author":"Brandenburg","year":"1998","journal-title":"Chem. Phys. Lipids"},{"key":"ref_50","first-page":"2008","article-title":"Biological activities of lipopolysaccharides are determined by the shape of their lipid A portion","volume":"267","author":"Schromm","year":"2000","journal-title":"JBIC J. Biol. Inorg. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1002\/eji.200323649","article-title":"The generalized endotoxic principle","volume":"33","author":"Seydel","year":"2003","journal-title":"Eur. J. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1718","DOI":"10.1080\/21505594.2018.1537730","article-title":"Pseudomonas aeruginosa LptE is crucial for LptD assembly, cell envelope integrity, antibiotic resistance and virulence","volume":"9","author":"Sciuto","year":"2018","journal-title":"Virulence"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1111\/j.1472-4669.2008.00157.x","article-title":"Gram-negative outer membrane vesicles: Beyond the cell surface","volume":"6","author":"McLean","year":"2008","journal-title":"Geobiology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1074\/jbc.AC118.006844","article-title":"Molecular conformation affects the interaction of the Pseudomonas quinolone signal with the bacterial outer membrane","volume":"294","author":"Li","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.2174\/138945012802002410","article-title":"Bacterial cell wall compounds as promising targets of antimicrobial agents I. Antimicrobial peptides and lipopolyamines","volume":"13","author":"Kowalski","year":"2012","journal-title":"Curr. Drug Targets"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e00478-15","DOI":"10.1128\/mBio.00478-15","article-title":"Reinforcing Lipid A Acylation on the Cell Surface of Acinetobacter baumannii Promotes Cationic Antimicrobial Peptide Resistance and Desiccation Survival","volume":"6","author":"Boll","year":"2015","journal-title":"mBio"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.tim.2011.04.005","article-title":"Pseudomonas aeruginosa: All roads lead to resistance","volume":"19","author":"Breidenstein","year":"2011","journal-title":"Trends Microbiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"11777","DOI":"10.1021\/bi000810n","article-title":"The Lipopolysaccharide Barrier: Correlation of Antibiotic Susceptibility with Antibiotic Permeability and Fluorescent Probe Binding Kinetics","volume":"39","author":"Snyder","year":"2000","journal-title":"Biochemistry"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"10758","DOI":"10.1021\/bi990867d","article-title":"Lipopolysaccharide Bilayer Structure: Effect of Chemotype, Core Mutations, Divalent Cations, and Temperature","volume":"38","author":"Snyder","year":"1999","journal-title":"Biochemistry"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2181","DOI":"10.1021\/acs.jcim.7b00271","article-title":"Polymyxin Binding to the Bacterial Outer Membrane Reveals Cation Displacement and Increasing Membrane Curvature in Susceptible but Not in Resistant Lipopolysaccharide Chemotypes","volume":"57","author":"Santos","year":"2017","journal-title":"J. Chem. Inf. Model."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"159","DOI":"10.2165\/00003495-200464020-00004","article-title":"Efflux-Mediated Drug Resistance in Bacteria","volume":"64","author":"Li","year":"2004","journal-title":"Drugs"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"3531","DOI":"10.1016\/j.jmb.2019.03.031","article-title":"Breaching the Barrier: Quantifying Antibiotic Permeability across Gram-negative Bacterial Membranes","volume":"431","author":"Cama","year":"2019","journal-title":"J. Mol. Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"25905","DOI":"10.1038\/srep25905","article-title":"Branched Peptide, B2088, Disrupts the Supramolecular Organization of Lipopolysaccharides and Sensitizes the Gram-negative Bacteria","volume":"6","author":"Lakshminarayanan","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Vaara, M. (2019). Polymyxin Derivatives that Sensitize Gram-Negative Bacteria to Other Antibiotics. Molecules, 24.","DOI":"10.3390\/molecules24020249"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/nmicrobiol.2017.28","article-title":"Pentamidine sensitizes Gram-negative pathogens to antibiotics and overcomes acquired colistin resistance","volume":"2","author":"Stokes","year":"2017","journal-title":"Nat. Microbiol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"00200-17","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_67","doi-asserted-by":"crossref","unstructured":"Akhoundsadegh, N., Belanger, C., and Hancock, R.E.W. (2019). Outer Membrane Interaction Kinetics of New Polymyxin B Analogs in Gram-Negative Bacilli. Antimicrob. Agents Chemother., 63.","DOI":"10.1128\/AAC.00935-19"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Torrens, G., P\u00e9rez-Gallego, M., Moy\u00e0, B., Munar-Bestard, M., Zamorano, L., Cabot, G., Bl\u00e1zquez, J., Ayala, J., Oliver, A., and Juan, C. (2017). Targeting the permeability barrier and peptidoglycan recycling pathways to disarm Pseudomonas aeruginosa against the innate immune system. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0181932"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1093\/femsre\/fux043","article-title":"Diversity and regulation of intrinsic beta-lactamases from non-fermenting and other Gram-negative opportunistic pathogens","volume":"41","author":"Juan","year":"2017","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Ying, L., Zhu, H., Fosso, M.Y., Garneau-Tsodikova, S., and Fredrick, K. (2020). Modified Aminoglycosides Bind Nucleic Acids in High-Molecular-Weight Complexes. Antibiotics, 9.","DOI":"10.3390\/antibiotics9020093"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Alfindee, M.N., Subedi, Y.P., Grilley, M.M., Takemoto, J.Y., and Chang, C.T. (2019). Antifungal Activities of 4\u2033,6\u2033-Disubstituted Amphiphilic Kanamycins. Molecules, 24.","DOI":"10.3390\/molecules24101882"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2426","DOI":"10.1039\/C9CS00556K","article-title":"A comprehensive overview of the medicinal chemistry of antifungal drugs: Perspectives and promise","volume":"49","author":"Howard","year":"2020","journal-title":"Chem. Soc. Rev."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1021\/acsinfecdis.8b00327","article-title":"Development of Fungal Selective Amphiphilic Kanamycin: Cost-Effective Synthesis and Use of Fluorescent Analogs for Mode of Action Investigation","volume":"5","author":"Subedi","year":"2018","journal-title":"ACS Infect. Dis."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4014\/jmb.1804.03051","article-title":"Antimicrobial Agents That Inhibit the Outer Membrane Assembly Machines of Gram-Negative Bacteria","volume":"29","author":"Choi","year":"2019","journal-title":"J. Microbiol. Biotechnol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/16\/8707\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:45:32Z","timestamp":1760165132000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/16\/8707"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,13]]},"references-count":74,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["ijms22168707"],"URL":"https:\/\/doi.org\/10.3390\/ijms22168707","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,13]]}}}