{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:18:45Z","timestamp":1787026725353,"version":"build-2736575974"},"reference-count":99,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T00:00:00Z","timestamp":1754524800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI114114"],"award-info":[{"award-number":["AI114114"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>\n                    Globally, it is predicted that by 2050, 10 million people will die annually because of infections with drug-resistant bacteria. Since antibacterial agents with novel mechanisms of action have not been developed in the past 30 years, there has been a surge of interest in combination therapies using existing drugs. The combination of aminoglycosides and colistin is often used to treat pneumonia caused by multidrug-resistant bacteria. The goal of this study is to investigate the relationship between the antibacterial activity of a peptide-neomycin library and polymyxin B in extensively drug-resistant and pandrug-resistant bacteria. The peptide-neomycin library contained conjugates with one or two amino acids linked to neomycin, rendering them unsuitable substrates for aminoglycoside-modifying enzymes. Neomycin- susceptible and neomycin-resistant members of\n                    <jats:italic>Acinetobacter baumannii, Klebsiella pneumoniae<\/jats:italic>\n                    , and\n                    <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                    were screened for synergy with polymyxin B using two-way checkerboard and time-kill methods. Most\n                    <jats:italic>A. baumannii<\/jats:italic>\n                    strains are resistant to amikacin, gentamicin, tobramycin, and plazomicin, and approximately half are susceptible to neomycin.\n                    <jats:italic>P. aeruginosa<\/jats:italic>\n                    strains have a similar resistance profile but was more susceptible to plazomicin.\n                    <jats:italic>K. pneumoniae<\/jats:italic>\n                    strains are most susceptible to a wide variety of aminoglycosides. Bacteria challenged with a combination of neomycin, other aminoglycosides, and polymyxin B exhibited an additive to indifferent relationship, whereas synergy was found with several neomycin-peptide conjugates containing cysteine, arginine, or tryptophan, lowering the minimal inhibitory concentration for the peptide-neomycin conjugate by 8-64-fold and polymyxin B by 2-8-fold. Cysteine, arginine, or tryptophan conjugates were the most effective against\n                    <jats:italic>A. baumannii<\/jats:italic>\n                    and\n                    <jats:italic>K. pneumoniae<\/jats:italic>\n                    carrying a 16S rRNA methyltransferase gene and a pandrug-resistant\n                    <jats:italic>P. aeruginosa<\/jats:italic>\n                    strain. Resistance to the combination of R-, C-, or RC-NEO conjugates and PB did not develop over a 14-day period in neomycin-susceptible strains of\n                    <jats:italic>A. baumannii, K. pneumoniae<\/jats:italic>\n                    , and\n                    <jats:italic>P. aeruginosa<\/jats:italic>\n                    . Based on this survey of the peptide-neomycin library, circumvention of aminoglycoside-modifying enzymes and alluding to bacterial resistance is an important step toward the design and development of peptide aminoglycoside-based motifs for antimicrobial drug development.\n                  <\/jats:p>","DOI":"10.3389\/fmicb.2025.1605813","type":"journal-article","created":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T05:29:06Z","timestamp":1754544546000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Synergistic action between peptide-neomycin conjugates and polymyxin B against multidrug-resistant gram-negative pathogens"],"prefix":"10.3389","volume":"16","author":[{"given":"Sandra","family":"Story","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liuwei","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain S.","family":"Leutou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dev P.","family":"Arya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1055\/s-0040-1713687","article-title":"Spectrum of aminoglycoside modifying enzymes in gram-negative bacteria causing human infections","volume":"12","author":"Aishwarya","year":"2020","journal-title":"J. Lab. Physicians"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e0270908","DOI":"10.1371\/journal.pone.0270908","article-title":"Synergistic activities of colistin combined with other antimicrobial agents against colistin-resistant Acinetobacter baumannii clinical isolates","volume":"17","author":"Almutairi","year":"2022","journal-title":"PLoS ONE"},{"key":"B3","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1038\/s41579-019-0218-1","article-title":"Mechanisms and clinical relevance of bacterial heteroresistance","volume":"17","author":"Andersson","year":"2019","journal-title":"Nat. Rev. Microbiol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"12273","DOI":"10.1002\/chem.202002258","article-title":"Aminoglycoside conjugation for RNA targeting: antimicrobials and beyond","volume":"26","author":"Aradi","year":"2020","journal-title":"Chem. Eur. J."},{"key":"B5","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1007\/b100446","article-title":"Aminoglycoside\u2013nucleic acid interactions: the case for neomycin","volume":"253","author":"Arya","year":"2005","journal-title":"DNA Binders Relat. Sub."},{"key":"B6","doi-asserted-by":"crossref","DOI":"10.1002\/9780470149676","volume-title":"Aminoglycoside Antibiotics: From Chemical Biology to Drug Discovery","author":"Arya","year":"2007"},{"key":"B7","doi-asserted-by":"publisher","first-page":"11614","DOI":"10.1038\/s41598-021-89446-3","article-title":"Structural and phylogenetic analyses of resistance to next-generation aminoglycosides conferred by AAC(2\u2032) enzymes","volume":"11","author":"Bassenden","year":"2021","journal-title":"Sci. Rep."},{"key":"B8","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1186\/s12866-023-03039-w","article-title":"In Vitro antibiotic combinations of Colistin, Meropenem, Amikacin, and Amoxicillin\/clavulanate against multidrug-resistant Klebsiella pneumonia isolated from patients with ventilator-associated pneumonia","volume":"23","author":"Bayatinejad","year":"2023","journal-title":"BMC Microbiol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1016\/j.carres.2011.01.015","article-title":"Synthesis and antibacterial activity of amphiphilic lysine-ligated neomycin B conjugates","volume":"346","author":"Bera","year":"2011","journal-title":"Carbohydr. Res."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1921","DOI":"10.1128\/AAC.00007-13","article-title":"Tryptophan inhibits biofilm formation by Pseudomonas aeruginosa","volume":"57","author":"Brandenburg","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"B11","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1186\/s12890-024-03032-7","article-title":"Efficacy of adjunctive inhaled colistin and tobramycin for ventilator-associated pneumonia: systematic review and meta-analysis","volume":"24","author":"Buend\u00eda","year":"2024","journal-title":"BMC Pulm. Med."},{"key":"B12","doi-asserted-by":"publisher","first-page":"930","DOI":"10.1080\/21505594.2018.1460187","article-title":"Phenotypic changes associated with Colistin resistance due to Lipopolysaccharide loss in Acinetobacter baumannii","volume":"9","author":"Carretero-Ledesma","year":"2018","journal-title":"Virulence"},{"key":"B13","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1021\/acsinfecdis.7b00254","article-title":"New application of neomycin B-bisbenzimidazole hybrids as antifungal agents","volume":"4","author":"Chandrika","year":"2018","journal-title":"ACS Infect. Dis."},{"key":"B14","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1081\/CAR-200059973","article-title":"Synthesis of neomycin-DNA\/peptide nucleic acid conjugates","volume":"24","author":"Charles","year":"2005","journal-title":"J. Carbohydr. Chem."},{"key":"B15","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1038\/msb.2011.71","article-title":"Systematic exploration of synergistic drug pairs","volume":"7","author":"Cokol","year":"2011","journal-title":"Mol. Syst. Biol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1128\/mr.51.3.341-350.1987","article-title":"Mechanism of bactericidal action of aminoglycosides","volume":"51","author":"Davis","year":"1987","journal-title":"Microbiol. Rev."},{"key":"B17","doi-asserted-by":"publisher","first-page":"e00181","DOI":"10.1128\/CMR.00181-19","article-title":"Antimicrobial resistance in ESKAPE pathogens","volume":"33","author":"De Oliveira","year":"2020","journal-title":"Clin. Microbiol. Rev."},{"key":"B18","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1021\/acsinfecdis.6b00176","article-title":"Antimicrobial activity, AME resistance, and A-site binding studies of anthraquinone\u2013neomycin conjugates","volume":"3","author":"Degtyareva","year":"2017","journal-title":"ACS Infect. Dis."},{"key":"B19","doi-asserted-by":"publisher","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":"B20","doi-asserted-by":"publisher","first-page":"e00043","DOI":"10.1128\/AAC.00043-17","article-title":"Rapid and consistent evolution of colistin resistance in extensively drug-resistant Pseudomonas aeruginosa during morbidostat culture","volume":"61","author":"D\u00f6\u00dfelmann","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1544","DOI":"10.1021\/mp500846u","article-title":"Improved biofilm antimicrobial activity of polyethylene glycol conjugated tobramycin compared to tobramycin in Pseudomonas aeruginosa biofilms","volume":"12","author":"Du","year":"2015","journal-title":"Mol. Pharm."},{"key":"B22","doi-asserted-by":"publisher","first-page":"960","DOI":"10.1345\/aph.18426","article-title":"Polymyxin B sulfate and colistin: old antibiotics for emerging multiresistant gram-negative bacteria","volume":"33","author":"Evans","year":"1999","journal-title":"Ann. Pharmacother."},{"key":"B23","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1016\/j.ijantimicag.2006.12.012","article-title":"Pandrug-resistant gram-negative bacteria: the dawn of the post-antibiotic era?","volume":"29","author":"Falagas","year":"2007","journal-title":"Int. J. Antimicrob. Agents"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1009297","DOI":"10.3389\/fmicb.2022.1009297","article-title":"Diversity and abundance of antibiotic resistance genes and their relationship with nutrients and land use of the inflow rivers of Taihu Lake","volume":"13","author":"Fernanda","year":"2022","journal-title":"Front. Microbiol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"e249","DOI":"10.1016\/j.jinf.2005.04.003","article-title":"Amikacin and colistin for treatment of Acinetobacter baumannii meningitis","volume":"51","author":"Fulnecky","year":"2005","journal-title":"J. Infect."},{"key":"B26","doi-asserted-by":"publisher","first-page":"3960","DOI":"10.1128\/AAC.00660-12","article-title":"RmtF, a new member of the aminoglycoside resistance 16S rRNA N7 G1405 methyltransferase family","volume":"56","author":"Galimand","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"B27","doi-asserted-by":"publisher","first-page":"2949","DOI":"10.1128\/AAC.49.7.2949-2953.2005","volume":"49","author":"Galimand","year":"2005","journal-title":"1548 Antimicrob. Agents Chemother."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1212","DOI":"10.1021\/acs.bioconjchem.2c00467","article-title":"Designing new hybrid antibiotics: proline-rich antimicrobial peptides conjugated to the aminoglycoside tobramycin","volume":"34","author":"Gambato","year":"2023","journal-title":"Bioconjug. Chem."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.1039\/C8MD00092A","article-title":"Targeting miRNA by tunable small molecule binders: peptidic aminosugar mediated interference in miR-21 biogenesis reverts epithelial to mesenchymal transition","volume":"9","author":"Ghosh","year":"2018","journal-title":"Medchemcomm"},{"key":"B30","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1038\/s42003-021-02261-4","article-title":"Structural basis for plazomicin antibiotic action and resistance","volume":"4","author":"Golkar","year":"2021","journal-title":"Commun. Biol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1159\/000119741","article-title":"In vitro activities of various antibiotics, alone and in combination with colistin methanesulfonate, against Pseudomonas aeruginosa strains isolated from cystic fibrosis patients","volume":"54","author":"G\u00fczel","year":"2008","journal-title":"Chemotherapy"},{"key":"B32","doi-asserted-by":"publisher","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":"B33","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1016\/S0891-5520(03)00058-8","article-title":"Polymyxins:: Pharmacology, pharmacokinetics, pharmacodynamics, and clinical applications","volume":"17","author":"Hermsen","year":"2003","journal-title":"Infect. Dis. Clin."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1585","DOI":"10.1086\/656788","article-title":"Colistin-tobramycin combinations are superior to monotherapy concerning the killing of biofilm Pseudomonas aeruginosa","volume":"202","author":"Herrmann","year":"2010","journal-title":"J. Infect. Dis."},{"key":"B35","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1183\/09031936.02.00248102","article-title":"A randomised clinical trial of nebulised tobramycin or colistin in cystic fibrosis","volume":"20","author":"Hodson","year":"2002","journal-title":"Eur. Respir. J."},{"key":"B36","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1038\/nrmicro2474","article-title":"Targeting bacterial membrane function: an underexploited mechanism for treating persistent infections","volume":"9","author":"Hurdle","year":"2011","journal-title":"Nat. Rev. Microbiol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"1068","DOI":"10.1002\/iub.531","article-title":"The genomics of Acinetobacter baumannii: insights into genome plasticity, antimicrobial resistance and pathogenicity","volume":"63","author":"Imperi","year":"2011","journal-title":"IUBMB Life"},{"key":"B38","doi-asserted-by":"publisher","first-page":"e01958","DOI":"10.1128\/AAC.01958-20","article-title":"Evolution of colistin resistance in the Klebsiella pneumoniae complex follows multiple evolutionary trajectories with variable effects on fitness and virulence characteristics","volume":"65","author":"Janssen","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2011.01.009","article-title":"High burden of antimicrobial resistance in Asia","author":"Jean ShioShin","year":"2011","journal-title":"Int. J. Antimicrob. Agents"},{"key":"B40","doi-asserted-by":"publisher","first-page":"1278","DOI":"10.1021\/cb5010367","article-title":"Rapid synthesis, RNA binding, and antibacterial screening of a peptidic-aminosugar (PA) library","volume":"10","author":"Jiang","year":"2015","journal-title":"ACS Chem. Biol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1039\/C5MD00427F","article-title":"Arginine-linked neomycin B dimers: synthesis, rRNA binding, and resistance enzyme activity","volume":"7","author":"Jin","year":"2016","journal-title":"Medchemcomm"},{"key":"B42","doi-asserted-by":"publisher","first-page":"e05992020","DOI":"10.1590\/0037-8682-0599-2020","article-title":"Role of aminoglycoside-modifying enzymes and 16S rRNA methylase (ArmA) in resistance of Acinetobacter baumannii clinical isolates against aminoglycosides","volume":"54","author":"Jouybari","year":"2021","journal-title":"Rev. Soc. Bras. Med. Trop."},{"key":"B43","doi-asserted-by":"publisher","first-page":"1235","DOI":"10.1039\/C4MD00165F","article-title":"Multivalent amino sugars to recognize different TAR RNA conformations","volume":"5","author":"Kellish","year":"2014","journal-title":"Medchemcomm"},{"key":"B44","doi-asserted-by":"publisher","first-page":"4717","DOI":"10.1128\/AAC.00671-13","article-title":"Characterization of ribosomal binding and antibacterial activities using two orthogonal high-throughput screens","volume":"57","author":"King","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1163","DOI":"10.1093\/jac\/dkm305","article-title":"High rates of resistance to colistin and polymyxin B in subgroups of Acinetobacter baumannii isolates from Korea","volume":"60","author":"Ko","year":"2007","journal-title":"J. Antimicrob. Chemother."},{"key":"B46","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1111\/mmi.14403","article-title":"Cystine import is a valuable but risky process whose hazards Escherichia coli minimizes by inducing a cysteine exporter","volume":"113","author":"Korshunov","year":"2020","journal-title":"Mol. Microbiol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"4418","DOI":"10.1016\/j.tet.2018.07.012","article-title":"Rapid solid-phase syntheses of a peptidic-aminoglycoside library","volume":"74","author":"Kukielski","year":"2018","journal-title":"Tetrahedron"},{"key":"B48","doi-asserted-by":"publisher","first-page":"7159","DOI":"10.1021\/bi401088n","article-title":"Correction to click dimers to target HIV TAR RNA conformation","volume":"52","author":"Kumar","year":"2013","journal-title":"Biochemistry"},{"key":"B49","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1016\/j.febslet.2004.10.038","article-title":"Structure\u2013activity relationships of aminoglycoside-arginine conjugates that bind HIV-1 RNAs as determined by fluorescence and NMR spectroscopy","volume":"577","author":"Lapidot","year":"2004","journal-title":"FEBS Lett."},{"key":"B50","doi-asserted-by":"publisher","first-page":"e29650","DOI":"10.7759\/cureus.29650","article-title":"Community-acquired Acinetobacter radioresistens bacteremia in an immunocompetent host","volume":"14","author":"Lazarev","year":"2022","journal-title":"Cureus"},{"key":"B51","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/S0014-5793(99)00092-7","article-title":"Arginine-aminoglycoside conjugates that bind to HIV transactivation responsive element RNA in vitro","volume":"445","author":"Litovchick","year":"1999","journal-title":"FEBS Lett."},{"key":"B52","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.1093\/infdis\/jir476","article-title":"Acinetobacter baumannii resistant to colistin alters its antibiotic resistance profile: a case report from Spain","volume":"204","author":"L\u00f3pez-Rojas","year":"2011","journal-title":"J. Infect. Dis."},{"key":"B53","doi-asserted-by":"publisher","first-page":"4419","DOI":"10.1074\/jbc.R111.275578","article-title":"Analysis and functional prediction of reactive cysteine residues","volume":"287","author":"Marino","year":"2012","journal-title":"J. Biol. Chem."},{"key":"B54","doi-asserted-by":"publisher","first-page":"e202400189","DOI":"10.1002\/open.202400189","article-title":"Nucleic acid specificity, cellular localization and reduced toxicities of thiazole orange-neomycin conjugates","volume":"14","author":"McFarland","year":"2024","journal-title":"Chem. Open"},{"key":"B55","doi-asserted-by":"publisher","first-page":"3022","DOI":"10.1128\/AAC.01732-10","article-title":"Insertion sequence IS Aba11 is involved in colistin resistance and loss of lipopolysaccharide in Acinetobacter baumannii","volume":"55","author":"Moffatt","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"B56","doi-asserted-by":"publisher","first-page":"4971","DOI":"10.1128\/AAC.00834-10","article-title":"Colistin resistance in Acinetobacter baumannii is mediated by complete loss of lipopolysaccharide production","volume":"54","author":"Moffatt","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"B57","doi-asserted-by":"publisher","first-page":"1715","DOI":"10.3389\/fmicb.2016.01715","article-title":"The effect of colistin resistance-associated mutations on the fitness of Acinetobacter baumannii","volume":"7","author":"Mu","year":"2016","journal-title":"Front. Microbiol."},{"key":"B58","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1016\/S0140-6736(21)02724-0","article-title":"Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis","volume":"399","author":"Murray","year":"2022","journal-title":"Lancet"},{"key":"B59","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1016\/S0140-6736(24)01867-1","article-title":"Global burden of bacterial antimicrobial resistance 1990\u20132021: a systematic analysis with forecasts to 2050","volume":"404","author":"Naghavi","year":"2024","journal-title":"Lancet"},{"key":"B60","doi-asserted-by":"publisher","first-page":"5837","DOI":"10.1039\/C5SC01969A","article-title":"Potent inhibition of miR-27a by neomycin\u2013bisbenzimidazole conjugates","volume":"6","author":"Nahar","year":"2015","journal-title":"Chem. Sci."},{"key":"B61","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1128\/br.20.1.14-27.1956","article-title":"The properties and mode of action of the polymyxins","volume":"20","author":"Newton","year":"1956","journal-title":"Bacteriol. Rev."},{"key":"B62","doi-asserted-by":"publisher","first-page":"4573","DOI":"10.1128\/AAC.02463-14","article-title":"Antagonism between bacteriostatic and bactericidal antibiotics is prevalent","volume":"58","author":"Ocampo","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"B63","doi-asserted-by":"publisher","first-page":"800","DOI":"10.1016\/j.bbagen.2009.03.029","article-title":"Tryptophan end-tagging of antimicrobial peptides for increased potency against Pseudomonas aeruginosa","volume":"1790","author":"Pasupuleti","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"B64","doi-asserted-by":"publisher","first-page":"1252","DOI":"10.1128\/AAC.01304-07","article-title":"Acinetobacter radioresistens as a silent source of carbapenem resistance for Acinetobacter spp","volume":"52","author":"Poirel","year":"2008","journal-title":"Antimicrob. Agents Chemother."},{"key":"B65","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/j.drup.2010.08.003","article-title":"Aminoglycoside modifying enzymes","volume":"13","author":"Ramirez","year":"2010","journal-title":"Drug Resist. Updates"},{"key":"B66","doi-asserted-by":"publisher","first-page":"2267","DOI":"10.3390\/molecules22122267","article-title":"Amikacin: uses, resistance, and prospects for inhibition","volume":"22","author":"Ramirez","year":"2017","journal-title":"Molecules"},{"key":"B67","doi-asserted-by":"publisher","first-page":"5288","DOI":"10.1021\/acs.biochem.7b00703","article-title":"Eukaryotic ribosomal expansion segments as antimicrobial targets","volume":"56","author":"Ramos","year":"2017","journal-title":"Biochemistry"},{"key":"B68","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1056\/NEJM199901073400104","article-title":"Intermittent administration of inhaled tobramycin in patients with cystic fibrosis","volume":"340","author":"Ramsey","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"B69","doi-asserted-by":"publisher","first-page":"60","DOI":"10.3389\/fchem.2020.00060","article-title":"Surface dependent dual recognition of a G-quadruplex DNA with neomycin-intercalator conjugates","volume":"8","author":"Ranjan","year":"2020","journal-title":"Front. Chem."},{"key":"B70","doi-asserted-by":"publisher","first-page":"14228","DOI":"10.3390\/molecules181114228","article-title":"Targeting C-myc G-quadruplex: dual recognition by aminosugar-bisbenzimidazoles with varying linker lengths","volume":"18","author":"Ranjan","year":"2013","journal-title":"Molecules"},{"key":"B71","doi-asserted-by":"publisher","first-page":"5989","DOI":"10.1016\/j.bmcl.2016.10.076","article-title":"Linker dependent intercalation of bisbenzimidazole-aminosugars in an RNA duplex; selectivity in RNA vs. DNA binding","volume":"26","author":"Ranjan","year":"2016","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"B72","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/bs.mie.2019.05.027","article-title":"A fluorescent aminosugar to rapidly screen and study RNA binders","volume":"623","author":"Ranjan","year":"2019","journal-title":"Meth. Enzymol."},{"key":"B73","volume-title":"The design, synthesis, and microbiological investigation of tobramycin catecholate conjugates","author":"Rebizant","year":"2022"},{"key":"B74","doi-asserted-by":"publisher","first-page":"00430","DOI":"10.1128\/mBio.00430-16","article-title":"The Acinetobacter baumannii two-component system AdeRS regulates genes required for multidrug efflux, biofilm formation, and virulence in a strain-specific manner","volume":"7","author":"Richmond","year":"2016","journal-title":"MBio"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(25)00118-5","article-title":"The WHO bacterial priority pathogens list 2024: a prioritisation study to guide research, development, and public health strategies against antimicrobial resistance","author":"Sati","year":"2025","journal-title":"Lancet Infect. Dis. Open Access"},{"key":"B76","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.micpath.2015.07.009","article-title":"The effects of D-tyrosine combined with amikacin on the biofilms of Pseudomonas aeruginosa","volume":"86","author":"She","year":"2015","journal-title":"Microb. Pathog."},{"key":"B77","doi-asserted-by":"publisher","first-page":"9013","DOI":"10.22207\/JPAM.18.1.44","article-title":"Detection of multidrug-resistant integrons associated with Acinetobacter baumannii Isolated from clinical and environmental samples","volume":"18","author":"Shetty","year":"2024","journal-title":"J. Pure Appl. Microbiol."},{"key":"B78","doi-asserted-by":"publisher","first-page":"5244","DOI":"10.1128\/jb.173.16.5244-5246.1991","article-title":"Cysteine, even in low concentrations, induces transient amino acid starvation in Escherichia coli","volume":"173","author":"S\u00f8rensen","year":"1991","journal-title":"J. Bacteriol."},{"key":"B79","doi-asserted-by":"publisher","first-page":"4194","DOI":"10.1021\/acsinfecdis.4c00446","article-title":"A cell-based screening assay for rRNA-targeted drug discovery","volume":"10","author":"Story","year":"2024","journal-title":"ACS Infect. Dis."},{"key":"B80","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1016\/j.ejmech.2018.11.022","article-title":"Synthesis, antimicrobial activity, attenuation of aminoglycoside resistance in MRSA, and ribosomal A-site binding of pyrene-neomycin conjugates","volume":"163","author":"Story","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"B81","doi-asserted-by":"publisher","first-page":"338","DOI":"10.3390\/antibiotics10030338","article-title":"Cystic fibrosis: recent insights into inhaled antibiotic treatment and future perspectives","volume":"10","author":"Taccetti","year":"2021","journal-title":"Antibiotics"},{"key":"B82","doi-asserted-by":"publisher","first-page":"1384","DOI":"10.1128\/JB.01039-15","article-title":"Bacterial cysteine-inducible cysteine resistance systems","volume":"198","author":"Takumi","year":"2016","journal-title":"J. Bacteriol."},{"key":"B83","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3310\/hta17560","article-title":"Colistimethate sodium powder and tobramycin powder for inhalation for the treatment of chronic Pseudomonas aeruginosa lung infection in cystic fibrosis: systematic review and economic model","author":"Tappenden","year":"2013","journal-title":"Health Technol. Assess."},{"key":"B84","doi-asserted-by":"publisher","first-page":"860","DOI":"10.1007\/s11094-021-02510-0","article-title":"Potential for the development of a new generation of aminoglycoside antibiotics","volume":"55","author":"Tevyashova","year":"2021","journal-title":"Pharm. Chem. J."},{"key":"B85","doi-asserted-by":"publisher","first-page":"28291","DOI":"10.1038\/srep28291","article-title":"The induction and identification of novel Colistin resistance mutations in Acinetobacter baumannii and their implications","volume":"6","author":"Thi Khanh Nhu","year":"2016","journal-title":"Sci. Rep."},{"key":"B86","doi-asserted-by":"publisher","first-page":"1164","DOI":"10.3390\/antibiotics10101164","article-title":"Pseudomonas aeruginosa mexR and mexEF antibiotic efflux pump variants exhibit increased virulence","volume":"10","author":"Vaillancourt","year":"2021","journal-title":"Antibiotics"},{"key":"B87","doi-asserted-by":"publisher","first-page":"e01468","DOI":"10.1128\/spectrum.01468-22","article-title":"The efficacy of Colistin combined with amikacin or levofloxacin against Pseudomonas aeruginosa biofilm infection","volume":"10","author":"Wang","year":"2022","journal-title":"Microbiol. Spectr."},{"key":"B88","doi-asserted-by":"publisher","first-page":"1309","DOI":"10.1016\/j.bmc.2016.11.003","article-title":"Probing A \u2013form DNA: a fluorescent aminosugar probe and dual recognition by anthraquinone-neomycin conjugates","volume":"25","author":"Watkins","year":"2017","journal-title":"Bioorg. Med. Chem"},{"key":"B89","doi-asserted-by":"publisher","first-page":"e0144251","DOI":"10.1371\/journal.pone.0144251","article-title":"A pH sensitive high-throughput assay for miRNA binding of a peptide-aminoglycoside (PA) library","volume":"10","author":"Watkins","year":"","journal-title":"PLoS ONE"},{"key":"B90","doi-asserted-by":"publisher","first-page":"3899","DOI":"10.1128\/AAC.00861-15","article-title":"Influence of linker length and composition on enzymatic activity and ribosomal binding of neomycin dimers","volume":"59","author":"Watkins","year":"","journal-title":"Antimicrob. Agents Chemother."},{"key":"B91","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1007\/978-1-4939-9216-4_9","article-title":"Aminoglycoside functionalization as a tool for targeting nucleic acids","volume":"1973","author":"Watkins","year":"2019","journal-title":"Methods Mol. Biol."},{"key":"B92","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1016\/j.ab.2012.12.003","article-title":"A fluorescence-based screen for ribosome binding antibiotics","volume":"434","author":"Watkins","year":"2013","journal-title":"Anal. Biochem."},{"key":"B93","doi-asserted-by":"publisher","first-page":"4974","DOI":"10.1016\/j.bmcl.2009.07.079","article-title":"Triple recognition of B-DNA","volume":"19","author":"Willis","year":"2009","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"B94","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1021\/bi9016796","article-title":"Triple recognition of B-DNA by a neomycin\u2013hoechst 33258\u2013pyrene conjugate","volume":"49","author":"Willis","year":"2010","journal-title":"Biochemistry"},{"key":"B95","volume-title":"WHO Updates List of Drug-Resistant Bacteria Most Threatening to Human Health","year":"2024"},{"key":"B96","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1039\/b108171c","article-title":"Pyrene\u2013neomycin conjugate: dual recognition of a DNA triple helix","volume":"1","author":"Xue","year":"2002","journal-title":"Chem. Commun."},{"key":"B97","doi-asserted-by":"publisher","first-page":"906","DOI":"10.3390\/antibiotics11070906","article-title":"Research updates of plasmid-mediated aminoglycoside resistance 16S rRNA methyltransferase","volume":"11","author":"Yang","year":"2022","journal-title":"Antibiotics"},{"key":"B98","doi-asserted-by":"publisher","first-page":"1013939","DOI":"10.3389\/fmicb.2022.1013939","article-title":"Effects of amikacin, polymyxin-B, and sulbactam combination on the pharmacodynamic indices of mutant selection against multi-drug resistant Acinetobacter baumannii","volume":"13","author":"Zhu","year":"2022","journal-title":"Front. Microbiol."},{"key":"B99","doi-asserted-by":"publisher","first-page":"e00853","DOI":"10.1128\/AAC.00853-18","article-title":"Studies on aminoglycoside susceptibility identify a novel function of KsgA to secure translational fidelity during antibiotic stress","volume":"62","author":"Zou","year":"2018","journal-title":"Antimicrob. Agents Chemother."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2025.1605813\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T05:29:08Z","timestamp":1754544548000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2025.1605813\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,7]]},"references-count":99,"alternative-id":["10.3389\/fmicb.2025.1605813"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2025.1605813","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,7]]},"article-number":"1605813"}}