{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T03:10:15Z","timestamp":1791947415599,"version":"4.3.4"},"reference-count":90,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T00:00:00Z","timestamp":1764633600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T00:00:00Z","timestamp":1764633600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-RS-2024-00392205"],"award-info":[{"award-number":["NRF-RS-2024-00392205"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2025,12,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      The worldwide dissemination of colistin-resistant pathogens, despite global\n                        efforts, is a serious public health concern, considering that colistin is\n                        regarded as a last-resort antimicrobial agent for the clinical treatment of\n                        multidrug-resistant (MDR) Gram-negative bacterial infections. Since the\n                        development of novel strategies and technologies, such as limiting bacterial\n                        adaptation, is essential for our society, adaptive laboratory evolution\n                        (ALE) was conducted under colistin pressure to uncover poorly understood\n                        mechanisms of colistin adaptation and provide a fundamental basis for future\n                        technologies. In this study, two isolates of\n                      <jats:italic toggle=\"yes\">Klebsiella\n                            pneumoniae<\/jats:italic>\n                      were subjected to ALE under colistin pressure, with\n                        each isolate serving as the ancestor of three mutant strains resulting from\n                        independently conducted ALE experiments. Consequently, all strains surpassed\n                        the resistance threshold, and the resistant ratio of the bacterial\n                        population exceeded 60% by at least the seventh day of colistin pressure.\n                        Whole-genome resequencing revealed multiple gene variants potentially\n                        associated with colistin adaptation, warranting further assessment. The\n                        RNA-seq results from each stage of pressure revealed that in the early\n                        stage, pathways related to quorum sensing are involved, while in the later\n                        stage, pathways related to colistin target modification mechanisms were\n                        activated. This suggests that different reactions and pathways contribute to\n                        colistin survival at the early and later stages. The findings presented in\n                        this study will contribute to a deeper understanding of colistin adaptation\n                        in\n                      <jats:italic toggle=\"yes\">K. pneumoniae<\/jats:italic>\n                      and provide valuable insights for further\n                        studies aimed at establishing new strategies to prevent the further\n                        emergence of colistin-resistant\n                      <jats:italic toggle=\"yes\">K. pneumoniae<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      Nowadays, only a few treatment options remain for widespread\n                        multidrug-resistant (MDR) Gram-negative bacterial infections, including the\n                        old antibiotic colistin. However, colistin-resistant clinical pathogens are\n                        spreading globally, further limiting treatment options. The future does not\n                        look promising due to the increasing global use of antibiotics and the\n                        uncontrolled spread of MDR pathogens. Moreover, the development of novel\n                        antibiotics has been limited in the industrial sector due to the rapid\n                        adaptation of the clinical pathogens. Therefore, the hope relies solely on\n                        the development of novel strategies and technologies to manage bacterial\n                        infections or limit bacterial adaptations. In this study, a new strategy has\n                        been proposed based on findings from\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      colistin\n                        pressure to limit bacterial adaptation to colistin. Given the growing future\n                        concerns, the novel perspectives proposed in this study could provide a\n                        fundamental basis for developing novel materials or measures to limit\n                        antimicrobial adaptation in clinical environments.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.03428-24","type":"journal-article","created":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T13:36:01Z","timestamp":1761053761000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["Delineating molecular mechanisms on the acquisition of\n                    <i>in                        vitro-<\/i>\n                    adapted colistin-resistant\n                    <i>Klebsiella                        pneumoniae<\/i>\n                    by transcriptomic analysis"],"prefix":"10.1128","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-1454-9800","authenticated-orcid":false,"given":"Su Min","family":"Kyung","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04h9pn542","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Infectious Disease, College of Veterinary Medicine, Seoul National University","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun Ho","family":"Lee","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04h9pn542","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Infectious Disease, College of Veterinary Medicine, Seoul National University","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun-Seo","family":"Lee","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04h9pn542","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Infectious Disease, College of Veterinary Medicine, Seoul National University","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi-Rui","family":"Xiang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04h9pn542","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Infectious Disease, College of Veterinary Medicine, Seoul National University","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0548-0835","authenticated-orcid":true,"given":"Han Sang","family":"Yoo","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04h9pn542","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Infectious Disease, College of Veterinary Medicine, Seoul National University","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/femsre\/fux013"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.00078-15"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/124.4.394"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.1961.03620110004002"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1086\/514732"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/39.2.255"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms9020442"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.2147\/IDR.S427398"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2022.1076315"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.001104"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2023.1207441"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2020.586368"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1245993"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymben.2019.08.004"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.36.12.708"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1088"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3564"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1086\/285289"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2014.06.016"},{"key":"e_1_3_4_21_2","first-page":"R1","article-title":"Antibiotic resistance: a threat and\n                        challenge to society","volume":"1","author":"Dhawale A","year":"2014","unstructured":"Dhawale A, Rath A. 2014. Antibiotic resistance: a threat and challenge to society. Ann Appl Biosci 1:R1\u2013R6.","journal-title":"Ann Appl Biosci"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6976.2012.00345.x"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2022.791802"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2001.02669.x"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.187.6.2066-2076.2005"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.187.1.238-248.2005"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2021109990"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13567-019-0725-0"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1408691111"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgar.2023.12.018"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.resmic.2010.05.014"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.187.8.2870-2880.2005"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.181.20.6387-6395.1999"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1991.tb00787.x"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1097(90)90158-m"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1991.tb00788.x"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.564021"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)40096-2"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.175.20.6671-6678.1993"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.1983.tb00419.x"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.176.6.1695-1701.1994"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2007.07.144"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2008.03.007"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.2008.01437.x"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00688-09"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1995.tb02299.x"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M106962200"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2007.12.061"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.120.315037"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhazmat.2024.135588"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.3109\/10408418809104468"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01135388"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micres.2017.10.012"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0630018100"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi970453p"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-023-05302-2"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2016.02135"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja062940a"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1308098110"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkaa450"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01958-20"},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.1093\/femsre\/fuv038"},{"key":"e_1_3_4_63_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12866-023-03074-7"},{"key":"e_1_3_4_64_2","volume-title":"Performance standards for antimicrobial\n                        susceptibility testing","author":"CLSI","year":"2017","unstructured":"CLSI. 2017. Performance standards for antimicrobial susceptibility testing. Clinical and Laboratory Standards Institute, Wayne, PA."},{"key":"e_1_3_4_65_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00039-06"},{"key":"e_1_3_4_66_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3519"},{"key":"e_1_3_4_67_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-12-323"},{"key":"e_1_3_4_68_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks042"},{"key":"e_1_3_4_69_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"e_1_3_4_70_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2021.711077"},{"key":"e_1_3_4_71_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3176"},{"key":"e_1_3_4_72_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.211"},{"key":"e_1_3_4_73_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btae615"},{"key":"e_1_3_4_74_2","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_3_4_75_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.107524.110"},{"key":"e_1_3_4_76_2","doi-asserted-by":"publisher","unstructured":"Garrison E Marth G. 2016. Haplotype-based variant detection from short-read sequencing. arXiv. doi:10.48550\/arXiv.1207.3907","DOI":"10.48550\/arXiv.1207.3907"},{"key":"e_1_3_4_77_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp352"},{"key":"e_1_3_4_78_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr509"},{"key":"e_1_3_4_79_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-018-0051-x"},{"key":"e_1_3_4_80_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt755"},{"key":"e_1_3_4_81_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr670"},{"key":"e_1_3_4_82_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv710"},{"key":"e_1_3_4_83_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1009843107"},{"key":"e_1_3_4_84_2","doi-asserted-by":"publisher","DOI":"10.4161\/fly.19695"},{"key":"e_1_3_4_85_2","unstructured":"Andrews S. 2010. FastQC: a quality control tool for high throughput sequence data. Available from: http:\/\/www.bioinformatics.babraham.ac.uk\/projects\/fastqc"},{"key":"e_1_3_4_86_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btw354"},{"key":"e_1_3_4_87_2","doi-asserted-by":"publisher","DOI":"10.1093\/gigascience\/giab008"},{"key":"e_1_3_4_88_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1004873"},{"key":"e_1_3_4_89_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv566"},{"key":"e_1_3_4_90_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr330"},{"key":"e_1_3_4_91_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bti054"}],"container-title":["Microbiology Spectrum"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/spectrum.03428-24","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/spectrum.03428-24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T14:06:52Z","timestamp":1764684412000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/spectrum.03428-24"}},"subtitle":[],"editor":[{"given":"Joanna B.","family":"Goldberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,12,2]]},"references-count":90,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12,2]]}},"alternative-id":["10.1128\/spectrum.03428-24"],"URL":"https:\/\/doi.org\/10.1128\/spectrum.03428-24","relation":{},"ISSN":["2165-0497"],"issn-type":[{"value":"2165-0497","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,2]]},"assertion":[{"value":"2025-01-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e03428-24"}}