{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T03:16:10Z","timestamp":1780715770067,"version":"3.54.1"},"reference-count":70,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T00:00:00Z","timestamp":1759449600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T00:00:00Z","timestamp":1759449600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-025-18206-4","type":"journal-article","created":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T10:47:25Z","timestamp":1759488445000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A novel role for colistin as an efflux pump inhibitor in multidrug-resistant Klebsiella pneumoniae"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0891-7548","authenticated-orcid":false,"given":"Rajnikant","family":"Sharma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shekhar","family":"Yeshwante","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ngoc Minh","family":"Bui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Carbone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie","family":"Hicks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce E.","family":"Blough","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony","family":"Velkov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gauri G.","family":"Rao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,3]]},"reference":[{"key":"18206_CR1","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1111\/j.1574-6976.2011.00290.x","volume":"36","author":"H Nikaido","year":"2012","unstructured":"Nikaido, H. & Pag\u00e8s, J. M. Broad-specificity efflux pumps and their role in multidrug resistance of Gram-negative bacteria. FEMS Microbiol. Rev. 36, 340\u2013363 (2012).","journal-title":"FEMS Microbiol. Rev."},{"key":"18206_CR2","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1111\/j.1469-0691.2004.00763.x","volume":"10","author":"K Poole","year":"2004","unstructured":"Poole, K. Efflux-mediated multiresistance in Gram-negative bacteria. Clin. Microbiol. Infect. 10, 12\u201326 (2004).","journal-title":"Clin. Microbiol. Infect."},{"key":"18206_CR3","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1093\/jac\/dki171","volume":"56","author":"K Poole","year":"2005","unstructured":"Poole, K. Efflux-mediated antimicrobial resistance. J. Antimicrob. Chemother. 56, 20\u201351 (2005).","journal-title":"J. Antimicrob. Chemother."},{"key":"18206_CR4","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1038\/nrmicro1464","volume":"4","author":"LJ Piddock","year":"2006","unstructured":"Piddock, L. J. Multidrug-resistance efflux pumps? Not just for resistance. Nat. Rev. Microbiol. 4, 629 (2006).","journal-title":"Nat. Rev. Microbiol."},{"key":"18206_CR5","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1021\/acsinfecdis.6b00167","volume":"3","author":"N Abdali","year":"2017","unstructured":"Abdali, N. et al. Reviving antibiotics: efflux pump inhibitors that interact with acra, a membrane fusion protein of the AcrAB-TolC multidrug efflux pump. ACS Infect. Dis. 3, 89\u201398 (2017).","journal-title":"ACS Infect. Dis."},{"key":"18206_CR6","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1016\/j.bbrc.2014.05.090","volume":"453","author":"J Sun","year":"2014","unstructured":"Sun, J., Deng, Z. & Yan, A. Bacterial multidrug efflux pumps: mechanisms, physiology and Pharmacological exploitations. Biochem. Biophys. Res. Commun. 453, 254\u2013267 (2014).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"18206_CR7","doi-asserted-by":"publisher","first-page":"2460","DOI":"10.1002\/med.21591","volume":"39","author":"A Lamut","year":"2019","unstructured":"Lamut, A., Peterlin Ma\u0161i\u010d, L., Kikelj, D. & Toma\u0161i\u010d, T. Efflux pump inhibitors of clinically relevant multidrug resistant bacteria. Med. Res. Rev. 39, 2460\u20132504 (2019).","journal-title":"Med. Res. Rev."},{"key":"18206_CR8","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1128\/AAC.00715-09","volume":"54","author":"E Padilla","year":"2010","unstructured":"Padilla, E. et al. Klebsiella pneumoniae acrab efflux pump contributes to antimicrobial resistance and virulence. Antimicrob. Agents Chemother. 54, 177\u2013183 (2010).","journal-title":"Antimicrob. Agents Chemother."},{"key":"18206_CR9","doi-asserted-by":"publisher","first-page":"e00465","DOI":"10.1128\/mBio.00465-20","volume":"11","author":"E Grimsey","year":"2020","unstructured":"Grimsey, E. et al. Chlorpromazine and amitriptyline are substrates and inhibitors of the AcrB multidrug efflux pump. MBio 11, e00465\u2013e00420 (2020).","journal-title":"MBio"},{"key":"18206_CR10","doi-asserted-by":"publisher","first-page":"587","DOI":"10.3389\/fmicb.2015.00587","volume":"6","author":"J Anes","year":"2015","unstructured":"Anes, J., McCusker, M. P., Fanning, S. & Martins, M. The Ins and outs of RND efflux pumps in Escherichia coli. Front. Microbiol. 6, 587 (2015).","journal-title":"Front. Microbiol."},{"key":"18206_CR11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/ncomms13819","volume":"7","author":"C Oswald","year":"2016","unstructured":"Oswald, C., Tam, H. K. & Pos, K. M. Transport of lipophilic carboxylates is mediated by transmembrane helix 2 in multidrug transporter AcrB. Nat. Commun. 7, 1\u201310 (2016).","journal-title":"Nat. Commun."},{"key":"18206_CR12","doi-asserted-by":"publisher","first-page":"e4817","DOI":"10.1371\/journal.pone.0004817","volume":"4","author":"JM Pages","year":"2009","unstructured":"Pages, J. M. et al. Efflux pump, the masked side of beta-lactam resistance in Klebsiella pneumoniae clinical isolates. PLoS One. 4, e4817\u2013e4817 (2009).","journal-title":"PLoS One"},{"key":"18206_CR13","doi-asserted-by":"publisher","first-page":"750","DOI":"10.2174\/138945008785747824","volume":"9","author":"A Davin-Regli","year":"2008","unstructured":"Davin-Regli, A. et al. Membrane permeability and regulation of drug influx and efflux in enterobacterial pathogens. Curr. Drug Targets. 9, 750\u2013759 (2008).","journal-title":"Curr. Drug Targets"},{"key":"18206_CR14","doi-asserted-by":"publisher","first-page":"1848","DOI":"10.2174\/156802610793176620","volume":"10","author":"S Alibert-Franco","year":"2010","unstructured":"Alibert-Franco, S. et al. Efflux pumps of gram-negative bacteria, a new target for new molecules. Curr. Top. Med. Chem. 10, 1848\u20131857 (2010).","journal-title":"Curr. Top. Med. Chem."},{"issue":"12","key":"18206_CR15","doi-asserted-by":"publisher","first-page":"1555","DOI":"10.2165\/11317030-000000000-00000","volume":"69","author":"X Li","year":"2009","unstructured":"Li, X. & Nikaido, H. Efflux-mediated drug resistance in bacteria: an update. Drugs 69 (12), 1555\u20131623 (2009).","journal-title":"Drugs"},{"key":"18206_CR16","doi-asserted-by":"publisher","first-page":"862","DOI":"10.1016\/j.tim.2016.06.009","volume":"24","author":"GD Wright","year":"2016","unstructured":"Wright, G. D. Antibiotic adjuvants: rescuing antibiotics from resistance. Trends Microbiol. 24, 862\u2013871 (2016).","journal-title":"Trends Microbiol."},{"key":"18206_CR17","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1128\/CMR.00117-14","volume":"28","author":"XZ Li","year":"2015","unstructured":"Li, X. Z., Pl\u00e9siat, P. & Nikaido, H. The challenge of efflux-mediated antibiotic resistance in Gram-negative bacteria. Clin. Microbiol. Rev. 28, 337\u2013418 (2015).","journal-title":"Clin. Microbiol. Rev."},{"key":"18206_CR18","doi-asserted-by":"publisher","first-page":"468","DOI":"10.3390\/molecules22030468","volume":"22","author":"G Spengler","year":"2017","unstructured":"Spengler, G., Kincses, A., Gajd\u00e1cs, M. & Amaral, L. New roads leading to old destinations: efflux pumps as targets to reverse multidrug resistance in bacteria. Mol 22, 468 (2017).","journal-title":"Mol"},{"key":"18206_CR19","doi-asserted-by":"publisher","first-page":"702","DOI":"10.2174\/1389450116666151001103948","volume":"17","author":"Y Wang","year":"2016","unstructured":"Wang, Y., Venter, H. & Ma, S. Efflux pump inhibitors: a novel approach to combat efflux-mediated drug resistance in bacteria. Curr. Drug Targets. 17, 702\u2013719 (2016).","journal-title":"Curr. Drug Targets"},{"key":"18206_CR20","doi-asserted-by":"publisher","first-page":"3984","DOI":"10.1128\/AAC.46.12.3984-3986.2002","volume":"46","author":"A Mazzariol","year":"2002","unstructured":"Mazzariol, A., Zuliani, J., Cornaglia, G., Rossolini, G. M. & Fontana, R. AcrAB efflux system: expression and contribution to fluoroquinolone resistance in Klebsiella spp. Antimicrob. Agents Chemother. 46, 3984\u20133986 (2002).","journal-title":"Antimicrob. Agents Chemother."},{"key":"18206_CR21","doi-asserted-by":"publisher","first-page":"3118","DOI":"10.1128\/AAC.44.11.3118-3121.2000","volume":"44","author":"LJ Piddock","year":"2000","unstructured":"Piddock, L. J., White, D. G., Gensberg, K., Pumbwe, L. & Griggs, D. J. Evidence for an efflux pump mediating multiple antibiotic resistance in Salmonella enterica serovar typhimurium. Antimicrob. Agents Chemother. 44, 3118\u20133121 (2000).","journal-title":"Antimicrob. Agents Chemother."},{"key":"18206_CR22","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.ddstr.2006.05.005","volume":"3","author":"K Poole","year":"2006","unstructured":"Poole, K. & Lomovskaya, O. Can efflux inhibitors really counter resistance? Drug Discov Today Ther. Strateg. 3, 145\u2013152 (2006).","journal-title":"Drug Discov Today Ther. Strateg"},{"key":"18206_CR23","doi-asserted-by":"publisher","first-page":"421","DOI":"10.3389\/fmicb.2015.00421","volume":"6","author":"TJ Opperman","year":"2015","unstructured":"Opperman, T. J. & Nguyen, S. T. Recent advances toward a molecular mechanism of efflux pump Inhibition. Front. Microbiol. 6, 421 (2015).","journal-title":"Front. Microbiol."},{"key":"18206_CR24","doi-asserted-by":"publisher","first-page":"R127","DOI":"10.1016\/S1074-5521(00)00126-5","volume":"7","author":"GD Wright","year":"2000","unstructured":"Wright, G. D. Resisting resistance: new chemical strategies for battling superbugs. Chem. Biol. 7, R127\u2013R132 (2000).","journal-title":"Chem. Biol."},{"key":"18206_CR25","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1128\/AAC.45.1.105-116.2001","volume":"45","author":"O Lomovskaya","year":"2001","unstructured":"Lomovskaya, O. et al. Identification and characterization of inhibitors of multidrug resistance efflux pumps in Pseudomonas aeruginosa: novel agents for combination therapy. Antimicrob. Agents Chemother. 45, 105\u2013116 (2001).","journal-title":"Antimicrob. Agents Chemother."},{"key":"18206_CR26","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1093\/jac\/dki445","volume":"57","author":"WV Kern","year":"2006","unstructured":"Kern, W. V. et al. Effect of 1-(1-naphthylmethyl)-piperazine, a novel putative efflux pump inhibitor, on antimicrobial drug susceptibility in clinical isolates of Escherichia coli. J. Antimicrob. Chemother. 57, 339\u2013343 (2006).","journal-title":"J. Antimicrob. Chemother."},{"key":"18206_CR27","doi-asserted-by":"publisher","first-page":"7087","DOI":"10.1016\/j.bmc.2007.07.039","volume":"15","author":"K Yoshida","year":"2007","unstructured":"Yoshida, K. et al. MexAB-OprM specific efflux pump inhibitors in Pseudomonas aeruginosa. Part 7: highly soluble and in vivo active quaternary ammonium analogue D13-9001, a potential preclinical candidate. Bioorg. Med. Chem. 15, 7087\u20137097 (2007).","journal-title":"Bioorg. Med. Chem."},{"key":"18206_CR28","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1128\/AAC.01866-13","volume":"58","author":"TJ Opperman","year":"2014","unstructured":"Opperman, T. J. et al. Characterization of a novel Pyranopyridine inhibitor of the acrab efflux pump of Escherichia coli. Antimicrob. Agents Chemother. 58, 722\u2013733 (2014).","journal-title":"Antimicrob. Agents Chemother."},{"key":"18206_CR29","doi-asserted-by":"publisher","first-page":"910","DOI":"10.1016\/j.bcp.2005.12.008","volume":"71","author":"O Lomovskaya","year":"2006","unstructured":"Lomovskaya, O. & Bostian, K. A. Practical applications and feasibility of efflux pump inhibitors in the clinic\u2014a vision for applied use. Biochem. Pharmacol. 71, 910\u2013918 (2006).","journal-title":"Biochem. Pharmacol."},{"key":"18206_CR30","doi-asserted-by":"publisher","first-page":"5687","DOI":"10.1073\/pnas.1114944109","volume":"109","author":"T Eicher","year":"2012","unstructured":"Eicher, T., Cha, H. & Seeger, M. Transport of drugs by the multidrug transporter AcrB involves an access and a deep binding pocket that are separated by a switch-loop. Proc. Natl. Acad. Sci. U S A. 109, 5687\u20135692 (2012).","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"key":"18206_CR31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/9780470920541.ch1","volume":"77","author":"H Nikaido","year":"2011","unstructured":"Nikaido, H. Structure and mechanism of RND-type multidrug efflux pumps. Adv. Enzymol. Relat. Areas Mol. Biol. 77, 1 (2011).","journal-title":"Adv. Enzymol. Relat. Areas Mol. Biol."},{"key":"18206_CR32","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1128\/CMR.19.2.382-402.2006","volume":"19","author":"LJ Piddock","year":"2006","unstructured":"Piddock, L. J. Clinically relevant chromosomally encoded multidrug resistance efflux pumps in bacteria. Clin. Microbiol. Rev. 19, 382\u2013402 (2006).","journal-title":"Clin. Microbiol. Rev."},{"key":"18206_CR33","doi-asserted-by":"publisher","first-page":"73","DOI":"10.2174\/157489112799829710","volume":"7","author":"K Bhardwaj","year":"2012","unstructured":"Bhardwaj, K., Mohanty, P. & A. & Bacterial efflux pumps involved in multidrug resistance and their inhibitors: rejuvinating the antimicrobial chemotherapy. Recent. Pat. Anti-infect Drug Discov. 7, 73\u201389 (2012).","journal-title":"Recent. Pat. Anti-infect Drug Discov"},{"key":"18206_CR34","doi-asserted-by":"publisher","first-page":"2031","DOI":"10.2147\/IDR.S207844","volume":"12","author":"E Armengol","year":"2019","unstructured":"Armengol, E. et al. Efficacy of combinations of colistin with other antimicrobials involves membrane fluidity and efflux machinery. Infect. Drug Resist. 12, 2031\u20132038 (2019).","journal-title":"Infect. Drug Resist."},{"key":"18206_CR35","doi-asserted-by":"publisher","first-page":"2589","DOI":"10.1093\/jac\/dkv135","volume":"70","author":"N Abdul Rahim","year":"2015","unstructured":"Abdul Rahim, N. et al. Synergistic killing of NDM-producing MDR Klebsiella pneumoniae by two \u2018old\u2019antibiotics\u2014polymyxin B and Chloramphenicol. J. Antimicrob. Chemother. 70, 2589\u20132597 (2015).","journal-title":"J. Antimicrob. Chemother."},{"key":"18206_CR36","doi-asserted-by":"publisher","first-page":"1223","DOI":"10.3390\/molecules21091223","volume":"21","author":"H Rudilla","year":"2016","unstructured":"Rudilla, H. et al. Synergistic antipseudomonal effects of synthetic peptide AMP38 and carbapenems. Mol 21, 1223 (2016).","journal-title":"Mol"},{"key":"18206_CR37","doi-asserted-by":"publisher","first-page":"686","DOI":"10.1126\/science.aar7981","volume":"362","author":"I El Meouche","year":"2018","unstructured":"El Meouche, I. & Dunlop, M. J. Heterogeneity in efflux pump expression predisposes antibiotic-resistant cells to mutation. Sci 362, 686\u2013690. https:\/\/doi.org\/10.1126\/science.aar7981 (2018).","journal-title":"Sci"},{"key":"18206_CR38","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1126\/science.aav6390","volume":"364","author":"S Nolivos","year":"2019","unstructured":"Nolivos, S. et al. Role of AcrAB-TolC multidrug efflux pump in drug-resistance acquisition by plasmid transfer. Sci 364, 778\u2013782 (2019).","journal-title":"Sci"},{"key":"18206_CR39","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1038\/s41559-018-0547-x","volume":"2","author":"DR Gifford","year":"2018","unstructured":"Gifford, D. R. et al. Identifying and exploiting genes that potentiate the evolution of antibiotic resistance. Nat. Ecoi Evol. 2, 1033\u20131039 (2018).","journal-title":"Nat. Ecoi Evol."},{"key":"18206_CR40","doi-asserted-by":"publisher","first-page":"3970","DOI":"10.1038\/s41467-020-17735-y","volume":"11","author":"A Papkou","year":"2020","unstructured":"Papkou, A., Hedge, J., Kapel, N., Young, B. & MacLean, R. C. Efflux pump activity potentiates the evolution of antibiotic resistance across S. aureus isolates. Nat. Commun. 11, 3970 (2020).","journal-title":"Nat. Commun."},{"key":"18206_CR41","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1471-2334-5-1","volume":"5","author":"ME Falagas","year":"2005","unstructured":"Falagas, M. E. et al. Toxicity after prolonged (more than four weeks) administration of intravenous colistin. BMC Infect. Dis. 5, 1\u20138 (2005).","journal-title":"BMC Infect. Dis."},{"key":"18206_CR42","doi-asserted-by":"publisher","first-page":"1300","DOI":"10.1093\/cid\/cit453","volume":"57","author":"DS Akajagbor","year":"2013","unstructured":"Akajagbor, D. S. et al. Higher incidence of acute kidney injury with intravenous colistimethate sodium compared with polymyxin B in critically ill patients at a tertiary care medical center. Clin. Infect. Dis. 57, 1300\u20131303 (2013).","journal-title":"Clin. Infect. Dis."},{"key":"18206_CR43","doi-asserted-by":"publisher","first-page":"879","DOI":"10.1093\/cid\/cir611","volume":"53","author":"JM Pogue","year":"2011","unstructured":"Pogue, J. M. et al. Incidence of and risk factors for colistin-associated nephrotoxicity in a large academic health system. Clin. Infect. Dis. 53, 879\u2013884 (2011).","journal-title":"Clin. Infect. Dis."},{"key":"18206_CR44","doi-asserted-by":"publisher","first-page":"857","DOI":"10.7326\/0003-4819-72-6-857","volume":"72","author":"J Koch-Weser","year":"1970","unstructured":"Koch-Weser, J. et al. Adverse effects of sodium colistimethate: manifestations and specific reaction rates during 317 courses of therapy. Ann. Intern. Med. 72, 857\u2013868 (1970).","journal-title":"Ann. Intern. Med."},{"key":"18206_CR45","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1016\/j.ijantimicag.2005.09.004","volume":"26","author":"ME Falagas","year":"2005","unstructured":"Falagas, M. E., Fragoulis, K. N., Kasiakou, S. K., Sermaidis, G. J. & Michalopoulos, A. Nephrotoxicity of intravenous colistin: a prospective evaluation. Int. J. Antimicrob. Agents. 26, 504\u2013507 (2005).","journal-title":"Int. J. Antimicrob. Agents"},{"key":"18206_CR46","doi-asserted-by":"publisher","first-page":"1724","DOI":"10.1086\/599225","volume":"48","author":"JD Hartzell","year":"2009","unstructured":"Hartzell, J. D. et al. Nephrotoxicity associated with intravenous colistin (colistimethate sodium) treatment at a tertiary care medical center. Clin. Infect. Dis. 48, 1724\u20131728 (2009).","journal-title":"Clin. Infect. Dis."},{"key":"18206_CR47","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1471-2334-13-380","volume":"13","author":"L Sorl\u00ed","year":"2013","unstructured":"Sorl\u00ed, L. et al. Trough colistin plasma level is an independent risk factor for nephrotoxicity: a prospective observational cohort study. BMC Infect. Dis. 13, 1\u20139 (2013).","journal-title":"BMC Infect. Dis."},{"key":"18206_CR48","doi-asserted-by":"publisher","first-page":"101128aac01367","DOI":"10.1128\/AAC.01367-17","volume":"61","author":"A Forrest","year":"2017","unstructured":"Forrest, A. et al. Pharmacokinetic\/toxicodynamic analysis of colistin-associated acute kidney injury in critically ill patients. Antimicrob. Agents Chemother. 61, 101128aac01367\u2013101128aac01317 (2017).","journal-title":"Antimicrob. Agents Chemother."},{"key":"18206_CR49","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1016\/j.ijantimicag.2016.08.020","volume":"48","author":"JP Horcajada","year":"2016","unstructured":"Horcajada, J. P. et al. Validation of a colistin plasma concentration breakpoint as a predictor of nephrotoxicity in patients treated with colistin methanesulfonate. Int. J. Antimicrob. Agents. 48, 725\u2013727 (2016).","journal-title":"Int. J. Antimicrob. Agents"},{"key":"18206_CR50","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1093\/cid\/ciw839","volume":"64","author":"RL Nation","year":"2017","unstructured":"Nation, R. L. et al. Dosing guidance for intravenous colistin in critically ill patients. Clin. Infect. Dis. 64, 565\u2013571 (2017).","journal-title":"Clin. Infect. Dis."},{"key":"18206_CR51","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1016\/j.ijantimicag.2016.09.010","volume":"48","author":"TB Tran","year":"2016","unstructured":"Tran, T. B. et al. Pharmacokinetics\/pharmacodynamics of colistin and polymyxin B: are we there yet? Int. J. Antimicrob. Agents. 48, 592\u2013597 (2016).","journal-title":"Int. J. Antimicrob. Agents"},{"key":"18206_CR52","doi-asserted-by":"publisher","first-page":"1381","DOI":"10.1128\/AAC.00327-13","volume":"58","author":"GG Rao","year":"2014","unstructured":"Rao, G. G. et al. New dosing strategies for an old antibiotic: pharmacodynamics of front-loaded regimens of colistin at simulated pharmacokinetics in patients with kidney or liver disease. Antimicrob. Agents Chemother. 58, 1381\u20131388 (2014).","journal-title":"Antimicrob. Agents Chemother."},{"key":"18206_CR53","doi-asserted-by":"publisher","first-page":"1328","DOI":"10.3390\/biology11091328","volume":"11","author":"R Alenazy","year":"2022","unstructured":"Alenazy, R. Drug efflux pump inhibitors: a promising approach to counter multidrug resistance in Gram-negative pathogens by targeting AcrB protein from AcrAB-TolC multidrug efflux pump from Escherichia coli. Biol 11, 1328 (2022).","journal-title":"Biol"},{"key":"18206_CR54","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1136\/thx.52.11.987","volume":"52","author":"S Conway","year":"1997","unstructured":"Conway, S. et al. Intravenous colistin sulphomethate in acute respiratory exacerbations in adult patients with cystic fibrosis. Thorax 52, 987\u2013993 (1997).","journal-title":"Thorax"},{"key":"18206_CR55","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1128\/AAC.47.3.905-909.2003","volume":"47","author":"BW Gunderson","year":"2003","unstructured":"Gunderson, B. W. et al. Synergistic activity of colistin and Ceftazidime against multiantibiotic-resistant Pseudomonas aeruginosa in an in vitro pharmacodynamic model. Antimicrob. Agents Chemother. 47, 905\u2013909 (2003).","journal-title":"Antimicrob. Agents Chemother."},{"key":"18206_CR56","doi-asserted-by":"publisher","first-page":"690","DOI":"10.1046\/j.1469-0691.2000.00169.x","volume":"6","author":"C Tascini","year":"2000","unstructured":"Tascini, C., Ferranti, S., Messina, F. & Menichetti, F. In vitro and in vivo synergistic activity of colistin, rifampin, and Amikacin against a multiresistant Pseudomonas aeruginosa isolate. Clin. Microbiol. Infect. 6, 690\u2013691 (2000).","journal-title":"Clin. Microbiol. Infect."},{"key":"18206_CR57","unstructured":"CLSI. Performance standards for antimicrobial susceptibility testing; twenty-fifth informational supplement M100-S25. Clinical and Laboratory Standards Institute, Wayne, PA, (2015)."},{"key":"18206_CR58","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/1756-0500-7-13","volume":"7","author":"TW Huang","year":"2014","unstructured":"Huang, T. W. et al. Capsule deletion via a \u03bb-Red knockout system perturbs biofilm formation and fimbriae expression in Klebsiella pneumoniae MGH 78578. BMC Res. Notes. 7, 13 (2014).","journal-title":"BMC Res. Notes"},{"key":"18206_CR59","doi-asserted-by":"publisher","first-page":"1541","DOI":"10.1073\/pnas.0337542100","volume":"100","author":"B Gust","year":"2003","unstructured":"Gust, B., Challis, G. L., Fowler, K., Kieser, T. & Chater, K. F. PCR-targeted streptomyces gene replacement identifies a protein domain needed for biosynthesis of the sesquiterpene soil odor Geosmin. Proc. Natl. Acad. Sci. U S A. 100, 1541\u20131546. https:\/\/doi.org\/10.1073\/pnas.0337542100 (2003).","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"key":"18206_CR60","doi-asserted-by":"publisher","first-page":"21964","DOI":"10.1074\/jbc.272.35.21964","volume":"272","author":"A Ocaktan","year":"1997","unstructured":"Ocaktan, A., Yoneyama, H. & Nakae, T. Use of fluorescence probes to monitor function of the subunit proteins of the MexA-MexB-OprM drug extrusion machinery in Pseudomonas aeruginosa. J. Biol. Chem. 272, 21964\u201321969 (1997).","journal-title":"J. Biol. Chem."},{"key":"18206_CR61","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1754-1611-3-18","volume":"3","author":"L Paix\u00e3o","year":"2009","unstructured":"Paix\u00e3o, L. et al. Fluorometric determination of ethidium bromide efflux kinetics in Escherichia coli. J. Biol. Eng. 3, 1\u201313 (2009).","journal-title":"J. Biol. Eng."},{"key":"18206_CR62","doi-asserted-by":"publisher","first-page":"1594","DOI":"10.1093\/jac\/dkt052","volume":"68","author":"G Richmond","year":"2013","unstructured":"Richmond, G., Chua, K. L. & Piddock, L. Efflux in Acinetobacter baumannii can be determined by measuring accumulation of H33342 (bis-benzamide). J. Antimicrob. Chemother. 68, 1594\u20131600 (2013).","journal-title":"J. Antimicrob. Chemother."},{"key":"18206_CR63","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1016\/j.ab.2008.10.041","volume":"385","author":"H Cai","year":"2009","unstructured":"Cai, H., Rose, K., Liang, L. H., Dunham, S. & Stover, C. Development of a liquid chromatography\/mass spectrometry-based drug accumulation assay in Pseudomonas aeruginosa. Anal. Biochem. 385, 321\u2013325 (2009).","journal-title":"Anal. Biochem."},{"key":"18206_CR64","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1093\/jac\/43.suppl_3.55","volume":"43","author":"H Drugeon","year":"1999","unstructured":"Drugeon, H., Juvin, M. & Bryskier, A. Relative potential for selection of fluoroquinolone-resistant Streptococcus pneumoniae strains by levofloxacin: comparison with ciprofloxacin, Sparfloxacin and Ofloxacin. J. Antimicrob. Chemother. 43, 55\u201359 (1999).","journal-title":"J. Antimicrob. Chemother."},{"key":"18206_CR65","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1016\/j.ijantimicag.2016.10.025","volume":"49","author":"R Sharma","year":"2017","unstructured":"Sharma, R. et al. Polymyxin B in combination with meropenem against carbapenemase-producing Klebsiella pneumoniae: pharmacodynamics and morphological changes. Int. J. Antimicrob. Agents. 49, 224\u2013232 (2017).","journal-title":"Int. J. Antimicrob. Agents"},{"key":"18206_CR66","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/j.ijantimicag.2017.03.005","volume":"50","author":"T Bhattacharyya","year":"2017","unstructured":"Bhattacharyya, T., Sharma, A., Akhter, J. & Pathania, R. The small molecule IITR08027 restores the antibacterial activity of fluoroquinolones against multidrug-resistant Acinetobacter baumannii by efflux Inhibition. Int. J. Antimicrob. Agents. 50, 219\u2013226 (2017).","journal-title":"Int. J. Antimicrob. Agents"},{"key":"18206_CR67","doi-asserted-by":"publisher","first-page":"1750","DOI":"10.1021\/jm030644s","volume":"47","author":"TA Halgren","year":"2004","unstructured":"Halgren, T. A. et al. Glide: a new approach for rapid, accurate Docking and scoring. 2. Enrichment factors in database screening. J. Med. Chem. 47, 1750\u20131759 (2004).","journal-title":"J. Med. Chem."},{"key":"18206_CR68","doi-asserted-by":"publisher","first-page":"1739","DOI":"10.1021\/jm0306430","volume":"47","author":"RA Friesner","year":"2004","unstructured":"Friesner, R. A. et al. Glide: a new approach for rapid, accurate Docking and scoring. 1. Method and assessment of Docking accuracy. J. Med. Chem. 47, 1739\u20131749 (2004).","journal-title":"J. Med. Chem."},{"key":"18206_CR69","doi-asserted-by":"publisher","first-page":"10731","DOI":"10.1038\/ncomms10731","volume":"7","author":"L Daury","year":"2016","unstructured":"Daury, L. et al. Tripartite assembly of RND multidrug efflux pumps. Nat. Commun. 7, 10731 (2016).","journal-title":"Nat. Commun."},{"key":"18206_CR70","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1038\/nature12300","volume":"500","author":"R Nakashima","year":"2013","unstructured":"Nakashima, R. et al. Structural basis for the Inhibition of bacterial multidrug exporters. Nat 500, 102 (2013).","journal-title":"Nat"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-18206-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-18206-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-18206-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T12:03:52Z","timestamp":1759493032000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-18206-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,3]]},"references-count":70,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["18206"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-18206-4","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,3]]},"assertion":[{"value":"4 January 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 August 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 October 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"34612"}}