{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T19:02:02Z","timestamp":1793041322636,"version":"4.5.0"},"reference-count":44,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100017700","name":"Henan Provincial Science and Technology Research Project","doi-asserted-by":"publisher","award":["252102310045"],"award-info":[{"award-number":["252102310045"]}],"id":[{"id":"10.13039\/501100017700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2025,10,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Colistin resistance in carbapenem-resistant\n                      <jats:italic toggle=\"yes\">Klebsiella pneumoniae<\/jats:italic>\n                      (CRKP) poses a significant global health challenge, as colistin remains the last-resort antibiotic for treating multidrug-resistant\n                      <jats:italic toggle=\"yes\">K. pneumoniae<\/jats:italic>\n                      infections. This study aimed to investigate the prevalence and molecular mechanisms underlying colistin resistance in CRKP (Col\n                      <jats:sup>r<\/jats:sup>\n                      -CRKP) isolates in Henan, China, from 2021 to 2024. The minimum inhibitory concentrations of colistin for 134\n                      <jats:italic toggle=\"yes\">K<\/jats:italic>\n                      .\n                      <jats:italic toggle=\"yes\">pneumoniae<\/jats:italic>\n                      isolates were determined using the broth microdilution method. Whole-genome sequencing was performed using the Illumina platform to identify carbapenemase genes and sequence types (STs). Colistin resistance mechanisms were investigated, including mutations in two-component systems (\n                      <jats:italic toggle=\"yes\">pmrA<\/jats:italic>\n                      \/\n                      <jats:italic toggle=\"yes\">pmrB<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">phoP<\/jats:italic>\n                      \/\n                      <jats:italic toggle=\"yes\">phoQ<\/jats:italic>\n                      ), inactivation of the\n                      <jats:italic toggle=\"yes\">mgrB<\/jats:italic>\n                      gene, and the presence of plasmid-mediated\n                      <jats:italic toggle=\"yes\">mcr<\/jats:italic>\n                      genes. Most isolates were collected from intensive care units (99\/134, 73.9%), with 48.5% (59\/134) of patients having no documented colistin exposure history. Notably, ST11 was the predominant sequence type among Col\n                      <jats:sup>r<\/jats:sup>\n                      -CRKP isolates (113\/134, 84.3%), all of which carried\n                      <jats:italic toggle=\"yes\">bla<\/jats:italic>\n                      <jats:sub>KPC-2<\/jats:sub>\n                      as the sole carbapenemase determinant. In contrast, seven non-carbapenemase-producing isolates exhibited phenotypic resistance to carbapenems. Genomic analysis revealed inactivation or loss of the\n                      <jats:italic toggle=\"yes\">mgrB<\/jats:italic>\n                      gene in 53.7% (72\/134) of isolates, predominantly due to insertion mutations (54\/72). Although 32.8% (44\/134) of isolates carried mutations in two-component systems, these alterations did not exhibit pathway-specific clustering. Intriguingly, plasmid-mediated\n                      <jats:italic toggle=\"yes\">mcr<\/jats:italic>\n                      genes were detected in only 1.5% (2\/134) of cases (\n                      <jats:italic toggle=\"yes\">mcr-8.2<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">mcr-1.1<\/jats:italic>\n                      ), while 22.4% (30\/134) of colistin-resistant strains lacked identifiable resistance determinants based on current detection methods. Our findings indicate that disruption of the\n                      <jats:italic toggle=\"yes\">mgrB<\/jats:italic>\n                      gene is the primary mechanism of colistin resistance in ST11 CRKP clones. The emergence of resistance in 48.5% of patients without prior colistin exposure, combined with low\n                      <jats:italic toggle=\"yes\">mcr<\/jats:italic>\n                      gene prevalence (1.5%) and unexplained resistance in 22.4% of isolates, suggests complex selective pressures beyond direct antimicrobial use. These findings underscore the urgent need for strengthened antimicrobial stewardship and the development of alternative therapeutic strategies to combat this high-risk pathogen.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        The global rise of colistin-resistant\n                        <jats:italic toggle=\"yes\">Klebsiella pneumoniae<\/jats:italic>\n                        , particularly in carbapenem-resistant\n                        <jats:italic toggle=\"yes\">Klebsiella pneumoniae<\/jats:italic>\n                        (CRKP) strains, has severely restricted treatment options for multidrug-resistant infections. Our study provides the first comprehensive molecular characterization of colistin resistance in CRKP in a large tertiary hospital in central China. We identified\n                        <jats:italic toggle=\"yes\">mgrB<\/jats:italic>\n                        disruption as the predominant resistance mechanism, while plasmid-mediated\n                        <jats:italic toggle=\"yes\">mcr<\/jats:italic>\n                        genes were rare. Notably, nearly half of the resistant isolates occurred in patients without prior colistin exposure, suggesting alternative selective pressures driving resistance. These findings highlight the complex dynamics of colistin resistance in CRKP and underscore the need for enhanced genomic surveillance and stewardship interventions to limit further dissemination.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.01049-25","type":"journal-article","created":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T13:01:20Z","timestamp":1756472480000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":6,"title":["Molecular characterization of colistin resistance in carbapenem-resistant\n                    <i>Klebsiella pneumoniae<\/i>\n                    from a tertiary hospital in China"],"prefix":"10.1128","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-8172-8653","authenticated-orcid":false,"given":"Saiqi","family":"Qi","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/056swr059","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haijun","family":"Li","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/056swr059","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University","place":["Zhengzhou, China"]},{"name":"Key Clinical Laboratory of Henan Province","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jilei","family":"Ma","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/056swr059","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University","place":["Zhengzhou, China"]},{"name":"Key Clinical Laboratory of Henan Province","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cailin","family":"Liu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/056swr059","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University","place":["Zhengzhou, China"]},{"name":"Key Clinical Laboratory of Henan Province","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Yi","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/056swr059","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University","place":["Zhengzhou, China"]},{"name":"Key Clinical Laboratory of Henan Province","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4389-541X","authenticated-orcid":true,"given":"Shijun","family":"Sun","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/056swr059","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University","place":["Zhengzhou, China"]},{"name":"Key Clinical Laboratory of Henan Province","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7987-8988","authenticated-orcid":false,"given":"Wanhai","family":"Wang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/056swr059","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University","place":["Zhengzhou, China"]},{"name":"Key Clinical Laboratory of Henan Province","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2018.00004"},{"key":"e_1_3_5_3_2","unstructured":"WHO bacterial priority pathogens list 2024: bacterial pathogens of public health importance to guide research development and strategies to prevent and control antimicrobial resistance. 2024. 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