{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T02:01:24Z","timestamp":1793325684719,"version":"4.5.0"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2017,3,6]],"date-time":"2017-03-06T00:00:00Z","timestamp":1488758400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2017,3,6]],"date-time":"2017-03-06T00:00:00Z","timestamp":1488758400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Microbiol"],"DOI":"10.1038\/nmicrobiol.2017.28","type":"journal-article","created":{"date-parts":[[2017,3,6]],"date-time":"2017-03-06T09:28:10Z","timestamp":1488792490000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":339,"title":["Pentamidine sensitizes Gram-negative pathogens to antibiotics and overcomes acquired colistin resistance"],"prefix":"10.1038","volume":"2","author":[{"given":"Jonathan M.","family":"Stokes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig R.","family":"MacNair","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bushra","family":"Ilyas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shawn","family":"French","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Philippe","family":"C\u00f4t\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catrien","family":"Bouwman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maya A.","family":"Farha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur O.","family":"Sieron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5267-7027","authenticated-orcid":false,"given":"Chris","family":"Whitfield","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian K.","family":"Coombes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric D.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,3,6]]},"reference":[{"key":"BFnmicrobiol201728_CR1","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1097\/QCO.0b013e328332e672","volume":"22","author":"RL Nation","year":"2009","unstructured":"Nation, R. L. & Li, J. Colistin in the 21st century. Curr. Opin. Infect. Dis. 22, 535\u2013543 (2009).","journal-title":"Curr. Opin. Infect. Dis."},{"key":"BFnmicrobiol201728_CR2","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/S1473-3099(15)00424-7","volume":"16","author":"YY Liu","year":"2016","unstructured":"Liu, Y. Y. et al. Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. Lancet Infect. Dis. 16, 161\u2013168 (2016).","journal-title":"Lancet Infect. Dis."},{"key":"BFnmicrobiol201728_CR3","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1038\/nrmicro3047","volume":"11","author":"BD Needham","year":"2013","unstructured":"Needham, B. D. & Trent, M. S. Fortifying the barrier: the impact of lipid A remodelling on bacterial pathogenesis. Nat. Rev. Microbiol. 11, 467\u2013481 (2013).","journal-title":"Nat. Rev. Microbiol."},{"key":"BFnmicrobiol201728_CR4","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1038\/nature17042","volume":"529","author":"ED Brown","year":"2016","unstructured":"Brown, E. D. & Wright, G. D. Antibacterial drug discovery in the resistance era. Nature 529, 336\u2013343 (2016).","journal-title":"Nature"},{"key":"BFnmicrobiol201728_CR5","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1128\/MMBR.67.4.593-656.2003","volume":"67","author":"H Nikaido","year":"2003","unstructured":"Nikaido, H. Molecular basis of bacterial outer membrane permeability revisited. Microbiol. Mol. Biol. Rev. 67, 593\u2013656 (2003).","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"BFnmicrobiol201728_CR6","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1093\/clinids\/7.5.625","volume":"7","author":"M Sands","year":"1985","unstructured":"Sands, M., Kron, M. A. & Brown, R. B. Pentamidine: a review. Rev. Infect. Dis. 7, 625\u2013634 (1985).","journal-title":"Rev. Infect. Dis."},{"key":"BFnmicrobiol201728_CR7","doi-asserted-by":"publisher","first-page":"e03574","DOI":"10.7554\/eLife.03574","volume":"3","author":"JM Stokes","year":"2014","unstructured":"Stokes, J. M., Davis, J. H., Mangat, C. S., Williamson, J. R. & Brown, E. D. Discovery of a small molecule that inhibits bacterial ribosome biogenesis. eLife 3, e03574 (2014).","journal-title":"eLife"},{"key":"BFnmicrobiol201728_CR8","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1016\/j.chembiol.2015.12.011","volume":"23","author":"JM Stokes","year":"2016","unstructured":"Stokes, J. M. et al. Cold stress makes Escherichia coli susceptible to glycopeptide antibiotics by altering outer membrane integrity. Cell Chem. Biol. 23, 267\u2013277 (2016).","journal-title":"Cell Chem. Biol."},{"key":"BFnmicrobiol201728_CR9","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1016\/j.bbapap.2008.11.005","volume":"1794","author":"AH Delcour","year":"2009","unstructured":"Delcour, A. H. Outer membrane permeability and antibiotic resistance. Biochim. Biophys. Acta 1794, 808\u2013816 (2009).","journal-title":"Biochim. Biophys. Acta"},{"key":"BFnmicrobiol201728_CR10","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1126\/science.8153625","volume":"264","author":"H Nikaido","year":"1994","unstructured":"Nikaido, H. Prevention of drug access to bacterial targets: permeability barriers and active efflux. Science 264, 382\u2013388 (1994).","journal-title":"Science"},{"key":"BFnmicrobiol201728_CR11","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1111\/cbdd.12478","volume":"85","author":"EE Gill","year":"2015","unstructured":"Gill, E. E., Franco, O. L. & Hancock, R. E. Antibiotic adjuvants: diverse strategies for controlling drug-resistant pathogens. Chem. Biol. Drug Des. 85, 56\u201378 (2015).","journal-title":"Chem. Biol. Drug Des."},{"key":"BFnmicrobiol201728_CR12","doi-asserted-by":"publisher","first-page":"18","DOI":"10.3390\/antibiotics4010018","volume":"4","author":"VI Band","year":"2015","unstructured":"Band, V. I. & Weiss, D. S. Mechanisms of antimicrobial peptide resistance in Gram-negative bacteria. Antibiotics 4, 18\u201341 (2015).","journal-title":"Antibiotics"},{"key":"BFnmicrobiol201728_CR13","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1016\/j.resmic.2012.10.020","volume":"163","author":"IA MacDonald","year":"2012","unstructured":"MacDonald, I. A. & Kuehn, M. J. Offense and defense: microbial membrane vesicles play both ways. Res. Microbiol. 163, 607\u2013618 (2012).","journal-title":"Res. Microbiol."},{"key":"BFnmicrobiol201728_CR14","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1128\/mr.56.3.395-411.1992","volume":"56","author":"M Vaara","year":"1992","unstructured":"Vaara, M. Agents that increase the permeability of the outer membrane. Microbiol. Rev. 56, 395\u2013411 (1992).","journal-title":"Microbiol. Rev."},{"key":"BFnmicrobiol201728_CR15","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1128\/AAC.24.1.114","volume":"24","author":"M Vaara","year":"1983","unstructured":"Vaara, M. & Vaara, T. Polycations as outer membrane-disorganizing agents. Antimicrob. Agents Chemother. 24, 114\u2013122 (1983).","journal-title":"Antimicrob. Agents Chemother."},{"key":"BFnmicrobiol201728_CR16","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1002\/jmr.549","volume":"14","author":"SA David","year":"2001","unstructured":"David, S. A. Towards a rational development of anti-endotoxin agents: novel approaches to sequestration of bacterial endotoxins with small molecules. J. Mol. Recognit. 14, 370\u2013387 (2001).","journal-title":"J. Mol. Recognit."},{"key":"BFnmicrobiol201728_CR17","doi-asserted-by":"publisher","first-page":"1654","DOI":"10.1093\/nar\/gkm1180","volume":"36","author":"T Sun","year":"2008","unstructured":"Sun, T. & Zhang, Y. Pentamidine binds to tRNA through non-specific hydrophobic interactions and inhibits aminoacylation and translation. Nucleic Acids Res. 36, 1654\u20131664 (2008).","journal-title":"Nucleic Acids Res."},{"key":"BFnmicrobiol201728_CR18","doi-asserted-by":"publisher","first-page":"958","DOI":"10.1128\/AAC.44.4.958-966.2000","volume":"44","author":"KE Miletti","year":"2000","unstructured":"Miletti, K. E. & Leibowitz, M. J. Pentamidine inhibition of group I intron splicing in Candida albicans correlates with growth inhibition. Antimicrob. Agents Chemother. 44, 958\u2013966 (2000).","journal-title":"Antimicrob. Agents Chemother."},{"key":"BFnmicrobiol201728_CR19","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.1021\/jm501449u","volume":"58","author":"W Zhu","year":"2015","unstructured":"Zhu, W. et al. Antibacterial drug leads: DNA and enzyme multitargeting. J. Med. Chem. 58, 1215\u20131227 (2015).","journal-title":"J. Med. Chem."},{"key":"BFnmicrobiol201728_CR20","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1128\/AAC.38.2.374","volume":"38","author":"I Ofek","year":"1994","unstructured":"Ofek, I. et al. Antibacterial synergism of polymyxin B nonapeptide and hydrophobic antibiotics in experimental Gram-negative infections in mice. Antimicrob. Agents Chemother. 38, 374\u2013377 (1994).","journal-title":"Antimicrob. Agents Chemother."},{"key":"BFnmicrobiol201728_CR21","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1021\/la504407v","volume":"31","author":"LA Clifton","year":"2014","unstructured":"Clifton, L. A. et al. Effect of divalent cation removal on the structure of Gram-negative bacterial outer membrane models. Langmuir 31, 404\u2013412 (2014).","journal-title":"Langmuir"},{"key":"BFnmicrobiol201728_CR22","doi-asserted-by":"publisher","first-page":"643","DOI":"10.3389\/fmicb.2014.00643","volume":"5","author":"AO Olaitan","year":"2014","unstructured":"Olaitan, A. O., Morand, S. & Rolain, J. M. Mechanisms of polymyxin resistance: acquired and intrinsic resistance in bacteria. Front. Microbiol. 5, 643 (2014).","journal-title":"Front. Microbiol."},{"key":"BFnmicrobiol201728_CR23","doi-asserted-by":"publisher","first-page":"2194","DOI":"10.1046\/j.1432-1033.2002.02875.x","volume":"269","author":"OV Bystrova","year":"2002","unstructured":"Bystrova, O. V. et al. Structural studies on the core and the O-polysaccharide repeating unit of Pseudomonas aeruginosa immunotype 1 lipopolysaccharide. Eur. J. Biochem. 269, 2194\u20132203 (2002).","journal-title":"Eur. J. Biochem."},{"key":"BFnmicrobiol201728_CR24","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1097\/00005792-194809000-00003","volume":"27","author":"EB Schoenbach","year":"1948","unstructured":"Schoenbach, E. B. & Greenspan, E. M. The pharmacology, mode of action and therapeutic potentialities of stilbamidine, pentamidine, propamidine and other aromatic diamidines: a review. Medicine (Baltimore) 27, 327\u2013377 (1948).","journal-title":"Medicine (Baltimore)"},{"key":"BFnmicrobiol201728_CR25","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1128\/jb.73.2.172-177.1957","volume":"73","author":"H Amos","year":"1957","unstructured":"Amos, H. & Vollmayer, E. Effect of pentamidine on the growth of Escherichia coli. J. Bacteriol. 73, 172\u2013177 (1957).","journal-title":"J. Bacteriol."},{"key":"BFnmicrobiol201728_CR26","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/j.mimet.2012.09.033","volume":"91","author":"M Ando","year":"2012","unstructured":"Ando, M. et al. In situ potentiometric method to evaluate bacterial outer membrane-permeabilizing ability of drugs: example using antiprotozoal diamidines. J. Microbiol. Methods 91, 497\u2013500 (2012).","journal-title":"J. Microbiol. Methods"},{"key":"BFnmicrobiol201728_CR27","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1378\/chest.110.1.136","volume":"110","author":"KT Yeung","year":"1996","unstructured":"Yeung, K. T., Chan, M. & Chan, C. K. The safety of i.v. pentamidine administered in an ambulatory setting. Chest 110, 136\u2013140 (1996).","journal-title":"Chest"},{"key":"BFnmicrobiol201728_CR28","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1038\/nchembio.559","volume":"7","author":"L Ejim","year":"2011","unstructured":"Ejim, L. et al. Combinations of antibiotics and nonantibiotic drugs enhance antimicrobial efficacy. Nat. Chem. Biol. 7, 348\u2013350 (2011).","journal-title":"Nat. Chem. Biol."},{"key":"BFnmicrobiol201728_CR29","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1038\/nrmicro1789","volume":"5","author":"L Dijkshoorn","year":"2007","unstructured":"Dijkshoorn, L., Nemec, A. & Seifert, H. An increasing threat in hospitals: multidrug-resistant Acinetobacter baumannii. Nat. Rev. Microbiol. 5, 939\u2013951 (2007).","journal-title":"Nat. Rev. Microbiol."},{"key":"BFnmicrobiol201728_CR30","doi-asserted-by":"publisher","first-page":"1295","DOI":"10.1093\/cid\/civ048","volume":"60","author":"ZA Qureshi","year":"2015","unstructured":"Qureshi, Z. A. et al. Colistin-resistant Acinetobacter baumannii: beyond carbapenem resistance. Clin. Infect. Dis. 60, 1295\u20131303 (2015).","journal-title":"Clin. Infect. Dis."},{"key":"BFnmicrobiol201728_CR31","doi-asserted-by":"publisher","first-page":"e00021","DOI":"10.1128\/mBio.00021-13","volume":"4","author":"BA Napier","year":"2013","unstructured":"Napier, B. A. et al. Clinical use of colistin induces cross-resistance to host antimicrobials in Acinetobacter baumannii. mBio 4, e00021\u201313 (2013).","journal-title":"mBio"},{"key":"BFnmicrobiol201728_CR32","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1016\/S1473-3099(16)00056-6","volume":"16","author":"H Du","year":"2016","unstructured":"Du, H., Chen, L., Tang, Y. W. & Kreiswirth, B. N. Emergence of the mcr-1 colistin resistance gene in carbapenem-resistant enterobacteriaceae. Lancet Infect. Dis. 16, 287\u2013288 (2016).","journal-title":"Lancet Infect. Dis."},{"key":"BFnmicrobiol201728_CR33","doi-asserted-by":"crossref","unstructured":"Baba, T. et al. Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection. Mol. Syst. Biol. 2, 2006.0008 (2006).","DOI":"10.1038\/msb4100050"},{"key":"BFnmicrobiol201728_CR34","doi-asserted-by":"publisher","first-page":"1314","DOI":"10.1177\/1087057114534298","volume":"19","author":"CS Mangat","year":"2014","unstructured":"Mangat, C. S., Bharat, A., Gehrke, S. S. & Brown, E. D. Rank ordering plate data facilitates data visualization and normalization in high-throughput screening. J. Biomol. Screen. 19, 1314\u20131320 (2014).","journal-title":"J. Biomol. Screen."},{"key":"BFnmicrobiol201728_CR35","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1091\/mbc.E15-08-0573","volume":"27","author":"S French","year":"2016","unstructured":"French, S. et al. A robust platform for chemical genomics in bacterial systems. Mol. Biol. Cell. 27, 1015\u20131025 (2016).","journal-title":"Mol. Biol. Cell."},{"key":"BFnmicrobiol201728_CR36","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1080\/10618600.1996.10474713","volume":"5","author":"R Ihaka","year":"1996","unstructured":"Ihaka, R. & Gentleman, R. R: a language for data analysis and graphics. J. Comp. Graph. Stat. 5, 299\u2013314 (1996).","journal-title":"J. Comp. Graph. Stat."},{"key":"BFnmicrobiol201728_CR37","doi-asserted-by":"publisher","first-page":"D605","DOI":"10.1093\/nar\/gks1027","volume":"41","author":"IM Keseler","year":"2013","unstructured":"Keseler, I. M. et al. Ecocyc: fusing model organism databases with systems biology. Nucleic Acids Res. 41, D605\u2013D612 (2013).","journal-title":"Nucleic Acids Res."},{"key":"BFnmicrobiol201728_CR38","doi-asserted-by":"publisher","first-page":"2040","DOI":"10.1126\/science.1064621","volume":"293","author":"PD Karp","year":"2001","unstructured":"Karp, P. D. Pathway databases: a case study in computational symbolic theories. Science 293, 2040\u20132044 (2001).","journal-title":"Science"},{"key":"BFnmicrobiol201728_CR39","doi-asserted-by":"publisher","first-page":"877","DOI":"10.1093\/bib\/bbv079","volume":"17","author":"PD Karp","year":"2016","unstructured":"Karp, P. D. et al. Pathway Tools version 19.0 update: software for pathway\/genome informatics and systems biology. Brief. Bioinform. 17, 877\u2013890 (2016).","journal-title":"Brief. Bioinform."},{"key":"BFnmicrobiol201728_CR40","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/jac\/dkg301","volume":"52","author":"FC Odds","year":"2003","unstructured":"Odds, F. C. Synergy, antagonism, and what the chequerboard puts between them. J. Antimicrob. Chemother. 52, 1 (2003).","journal-title":"J. Antimicrob. Chemother."},{"key":"BFnmicrobiol201728_CR41","doi-asserted-by":"publisher","first-page":"30085","DOI":"10.2807\/1560-7917.ES.2015.20.49.30085","volume":"20","author":"H Hasman","year":"2015","unstructured":"Hasman, H. et al. Detection of mcr-1 encoding plasmid-mediated colistin-resistant Escherichia coli isolates from human bloodstream infection and imported chicken meat, Denmark 2015. Euro Surveill. 20, 30085 (2015).","journal-title":"Euro Surveill."},{"key":"BFnmicrobiol201728_CR42","doi-asserted-by":"publisher","first-page":"1835","DOI":"10.1128\/JB.183.6.1835-1842.2001","volume":"183","author":"EA Groisman","year":"2001","unstructured":"Groisman, E. A. The pleiotropic two-component regulatory system PhoP-PhoQ. J. Bacteriol. 183, 1835\u20131842 (2001).","journal-title":"J. Bacteriol."},{"key":"BFnmicrobiol201728_CR43","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1093\/jac\/47.5.647","volume":"47","author":"AJ O'Neill","year":"2001","unstructured":"O'Neill, A. J., Cove, J. H. & Chopra, I. Mutation frequencies for resistance to fusidic acid and rifampicin in Staphylococcus aureus. J. Antimicrob. Chemother. 47, 647\u2013650 (2001).","journal-title":"J. Antimicrob. Chemother."},{"key":"BFnmicrobiol201728_CR44","doi-asserted-by":"publisher","first-page":"1289","DOI":"10.1128\/AAC.48.4.1289-1294.2004","volume":"48","author":"DH Mariam","year":"2004","unstructured":"Mariam, D. H., Mengistu, Y., Hoffner, S. E. & Andersson, D. I. Effect of rpoB mutations conferring rifampin resistance on fitness of Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 48, 1289\u20131294 (2004).","journal-title":"Antimicrob. Agents Chemother."}],"container-title":["Nature Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/nmicrobiol201728.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/nmicrobiol201728","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/nmicrobiol201728.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,22]],"date-time":"2024-06-22T16:48:05Z","timestamp":1719074885000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/nmicrobiol201728"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,3,6]]},"references-count":44,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2017,5]]}},"alternative-id":["BFnmicrobiol201728"],"URL":"https:\/\/doi.org\/10.1038\/nmicrobiol.2017.28","relation":{},"ISSN":["2058-5276"],"issn-type":[{"value":"2058-5276","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,3,6]]},"assertion":[{"value":"9 December 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 February 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 March 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"17028"}}