{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T15:49:18Z","timestamp":1790264958184,"version":"4.1.0"},"reference-count":57,"publisher":"Microbiology Society","issue":"3","license":[{"start":{"date-parts":[[2018,3,1]],"date-time":"2018-03-01T00:00:00Z","timestamp":1519862400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,3,1]]},"abstract":"<jats:p>\n                    Extensively drug-resistant\n                    <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                    (XDR-KP) infections cause high mortality and are disseminating globally. Identifying the genetic basis underpinning resistance allows for rapid diagnosis and treatment. XDR isolates sourced from Greece and Brazil, including 19 polymyxin-resistant and five polymyxin-susceptible strains, were subjected to whole genome sequencing. Seventeen of the 19 polymyxin-resistant isolates harboured variations upstream or within\n                    <jats:italic>mgrB<\/jats:italic>\n                    . The most common mutation identified was an insertion at nucleotide position 75 in\n                    <jats:italic>mgrB<\/jats:italic>\n                    via an IS\n                    <jats:italic>Kpn26<\/jats:italic>\n                    -like element in the ST258 lineage and IS\n                    <jats:italic>Kpn13<\/jats:italic>\n                    in one ST11 isolate. Three strains acquired an IS\n                    <jats:italic>1<\/jats:italic>\n                    element upstream of\n                    <jats:italic>mgrB<\/jats:italic>\n                    and another strain had an IS\n                    <jats:italic>Kpn25<\/jats:italic>\n                    insertion at 133\u2009bp. Other isolates had truncations (C28STOP, Q30STOP) or a missense mutation (D29E) affecting\n                    <jats:italic>mgrB<\/jats:italic>\n                    . Complementation assays revealed all\n                    <jats:italic>mgrB<\/jats:italic>\n                    perturbations contributed to resistance. Missense mutations in\n                    <jats:italic>phoQ<\/jats:italic>\n                    (T281M, G385C) were also found to facilitate resistance. Several variants in\n                    <jats:italic>phoPQ<\/jats:italic>\n                    co-segregating with the IS\n                    <jats:italic>Kpn26<\/jats:italic>\n                    -like insertion were identified as potential partial suppressor mutations. Three ST258 samples were found to contain subpopulations with different resistance-conferring mutations, including the IS\n                    <jats:italic>Kpn26<\/jats:italic>\n                    -like insertion colonizing with a novel mutation in\n                    <jats:italic>pmrB<\/jats:italic>\n                    (P158R), both confirmed via complementation assays. These findings highlight the broad spectrum of chromosomal modifications which can facilitate and regulate resistance against polymyxins in\n                    <jats:italic>K. pneumoniae<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1099\/mgen.0.000158","type":"journal-article","created":{"date-parts":[[2018,2,12]],"date-time":"2018-02-12T10:12:33Z","timestamp":1518430353000},"source":"Crossref","is-referenced-by-count":40,"title":["Multifactorial chromosomal variants regulate polymyxin resistance in extensively drug-resistant Klebsiella pneumoniae"],"prefix":"10.1099","volume":"4","author":[{"given":"Miranda E.","family":"Pitt","sequence":"first","affiliation":[{"name":"1\u200bInstitute for Molecular Bioscience, The University of Queensland, Brisbane, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alysha G.","family":"Elliott","sequence":"additional","affiliation":[{"name":"1\u200bInstitute for Molecular Bioscience, The University of Queensland, Brisbane, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minh Duc","family":"Cao","sequence":"additional","affiliation":[{"name":"1\u200bInstitute for Molecular Bioscience, The University of Queensland, Brisbane, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devika","family":"Ganesamoorthy","sequence":"additional","affiliation":[{"name":"1\u200bInstitute for Molecular Bioscience, The University of Queensland, Brisbane, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilias","family":"Karaiskos","sequence":"additional","affiliation":[{"name":"2\u200b6th Department of Internal Medicine, Hygeia General Hospital, Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Giamarellou","sequence":"additional","affiliation":[{"name":"2\u200b6th Department of Internal Medicine, Hygeia General Hospital, Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cely S.","family":"Abboud","sequence":"additional","affiliation":[{"name":"3\u200bInstituto Dante Pazzanese de Cardiologia, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A. T.","family":"Blaskovich","sequence":"additional","affiliation":[{"name":"1\u200bInstitute for Molecular Bioscience, The University of Queensland, Brisbane, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew A.","family":"Cooper","sequence":"additional","affiliation":[{"name":"1\u200bInstitute for Molecular Bioscience, The University of Queensland, Brisbane, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lachlan J. M.","family":"Coin","sequence":"additional","affiliation":[{"name":"1\u200bInstitute for Molecular Bioscience, The University of Queensland, Brisbane, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"345","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1128\/microbiolspec.PLAS-0016-2013"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1086\/592412"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1586\/eri.12.78"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00762-09"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2013.04.006"},{"key":"R6","first-page":"1","article-title":"Emerging carbapenem resistance among nosocomial isolates of Klebsiella pneumoniae in South India","volume":"1","author":"Mohamudha","year":"2010","journal-title":"Int J Pharma Bio Sci"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1086\/677170"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.03110-14"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1089\/mdr.2015.0282"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2016.09.025"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.2807\/1560-7917.ES2014.19.42.20939"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1590\/S0074-02762013000100019"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1590\/0037-8682-0041-2015"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2014.02.016"},{"key":"R15","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1128\/jb.97.1.448-452.1969","article-title":"Electron microscopic studies on mode of action of polymyxin","volume":"97","author":"Koike","year":"1969","journal-title":"J Bacteriol"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.29.5.781"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1038\/ja.2013.111"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1128\/jb.179.22.7040-7045.1997"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1021\/jm900999h"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1186\/1423-0127-17-60"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1996.0272n.x"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1177\/1753425913493337"},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.04037-14"},{"key":"R24","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2014.07.020"},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02981-15"},{"key":"R26","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01574-15"},{"key":"R27","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkr007"},{"key":"R28","doi-asserted-by":"publisher","DOI":"10.1038\/srep15082"},{"key":"R29","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(15)00424-7"},{"key":"R30","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(16)00010-4"},{"key":"R31","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(16)30527-8"},{"key":"R32","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01075-16"},{"key":"R33","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00543-17"},{"key":"R34","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2017.11.011"},{"key":"R35","volume-title":"Performance Standards for Antimicrobial Susceptibility Testing\u2013 Twenty-sixth Edition: Approved standard M100S","year":"2016"},{"key":"R36","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2011.03570.x"},{"key":"R37","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu170"},{"key":"R38","doi-asserted-by":"publisher","DOI":"10.1089\/cmb.2012.0021"},{"key":"R39","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt1226"},{"key":"R40","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.06094-11"},{"key":"R41","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dks261"},{"key":"R42","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2522"},{"key":"R43","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"key":"R44","first-page":"12073907","article-title":"Haplotype-based variant detection from short-read sequencing","author":"Garrison","year":"2012","journal-title":"arXiv preprint arXiv"},{"key":"R45","doi-asserted-by":"publisher","DOI":"10.4161\/fly.19695"},{"key":"R46","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv195"},{"key":"R47","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkj014"},{"key":"R48","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00084-14"},{"key":"R49","doi-asserted-by":"publisher","DOI":"10.1159\/000320943"},{"key":"R50","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dku323"},{"key":"R51","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01480-13"},{"key":"R52","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01456-16"},{"key":"R53","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201607336"},{"key":"R54","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01344-16"},{"key":"R55","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1321364111"},{"key":"R56","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.05391-11"},{"key":"R57","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2013.11.027"}],"container-title":["Microbial Genomics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.microbiologyresearch.org\/content\/journal\/mgen\/10.1099\/mgen.0.000158?crawler=true&mimetype=application\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,15]],"date-time":"2023-12-15T07:32:24Z","timestamp":1702625544000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.microbiologyresearch.org\/content\/journal\/mgen\/10.1099\/mgen.0.000158"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,3,1]]},"references-count":57,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2018,3,1]]}},"URL":"https:\/\/doi.org\/10.1099\/mgen.0.000158","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/134684","asserted-by":"object"}]},"ISSN":["2057-5858"],"issn-type":[{"value":"2057-5858","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,3,1]]}}}