{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T15:47:03Z","timestamp":1792424823739,"version":"4.5.0"},"reference-count":56,"publisher":"National Academy of Sciences","issue":"35","license":[{"start":{"date-parts":[[2024,8,16]],"date-time":"2024-08-16T00:00:00Z","timestamp":1723766400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32141002"],"award-info":[{"award-number":["32141002"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81991535"],"award-info":[{"award-number":["81991535"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"MOST | National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFD1800400"],"award-info":[{"award-number":["2022YFD1800400"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2024,8,27]]},"abstract":"<jats:p>\n                    The emergence of carbapenem-resistant hypervirulent\n                    <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                    (CR-hvKp) is a growing concern due to its high mortality and limited treatment options. Although hypermucoviscosity is crucial for CR-hvKp infection, the role of changes in bacterial mucoviscosity in the host colonization and persistence of CR-hvKp is not clearly defined. Herein, we observed a phenotypic switch of CR-hvKp from a hypermucoviscous to a hypomucoviscous state in a patient with scrotal abscess and urinary tract infection (UTI). This switch was attributed to decreased expression of\n                    <jats:italic>rmpADC<\/jats:italic>\n                    , the regulator of mucoid phenotype, caused by deletion of the upstream insertion sequence IS\n                    <jats:italic>Kpn26<\/jats:italic>\n                    . Postswitching, the hypomucoid variant showed a 9.0-fold decrease in mice sepsis mortality, a &gt;170.0-fold reduction in the ability to evade macrophage phagocytosis in vitro, and an 11.2- to 40.9-fold drop in growth rate in normal mouse serum. Conversely, it exhibited an increased residence time in the mouse urinary tract (21 vs. 6 d), as well as a 216.4-fold boost in adhesion to bladder epithelial cells and a 48.7% enhancement in biofilm production. Notably, the CR-hvKp mucoid switch was reproduced in an antibiotic-free mouse UTI model. The in vivo generation of hypomucoid variants was primarily associated with defective or low expression of\n                    <jats:italic>rmpADC<\/jats:italic>\n                    or capsule synthesis gene\n                    <jats:italic>wcaJ<\/jats:italic>\n                    , mediated by IS\n                    <jats:italic>Kpn26<\/jats:italic>\n                    insertion\/deletion or base-pair insertion. The spontaneous hypomucoid variants also outcompeted hypermucoid bacteria in the mouse urinary tract. Collectively, the IS\n                    <jats:italic>Kpn26<\/jats:italic>\n                    -associated mucoid switch in CR-hvKp signifies the antibiotic-independent host adaptive evolution, providing insights into the role of mucoid switch in the persistence of CR-hvKp.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2400446121","type":"journal-article","created":{"date-parts":[[2024,8,16]],"date-time":"2024-08-16T12:08:37Z","timestamp":1723810117000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":62,"title":["Adaptive evolution of carbapenem-resistant hypervirulent\n                    <i>Klebsiella pneumoniae<\/i>\n                    in the urinary tract of a single patient"],"prefix":"10.1073","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-5161-0347","authenticated-orcid":false,"given":"Shikai","family":"Song","sequence":"first","affiliation":[{"name":"National Key Laboratory of Veterinary Public Health and Safety, Department of Basic Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"},{"name":"Poultry Research Institute, Shandong Academy of Agricultural Science, Jinan 250100, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shixin","family":"Yang","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Veterinary Public Health and Safety, Department of Basic Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruicheng","family":"Zheng","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Veterinary Public Health and Safety, Department of Basic Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0417-158X","authenticated-orcid":false,"given":"Dandan","family":"Yin","sequence":"additional","affiliation":[{"name":"Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2605-5594","authenticated-orcid":false,"given":"Yue","family":"Cao","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Veterinary Public Health and Safety, Department of Basic Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Wang","sequence":"additional","affiliation":[{"name":"Shandong Animal Disease Prevention and Control Center, Jinan 250100, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Qiao","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Veterinary Public Health and Safety, Department of Basic Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rina","family":"Bai","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Veterinary Public Health and Safety, Department of Basic Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuge","family":"Wang","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Veterinary Public Health and Safety, Department of Basic Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9695-8224","authenticated-orcid":false,"given":"Wenjuan","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Basic Medical Science, Key Laboratory of Pathogenesis Mechanism and Control of Inflammatory-Autoimmune Diseases of Hebei Province, Hebei University, Baoding 071002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6396-8949","authenticated-orcid":false,"given":"Yanjun","family":"Dong","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Veterinary Public Health and Safety, Department of Basic Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Bai","sequence":"additional","affiliation":[{"name":"National Center for Food Safety Risk Assessment, Beijing 100022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6025-338X","authenticated-orcid":false,"given":"Hui","family":"Yang","sequence":"additional","affiliation":[{"name":"National Center for Food Safety Risk Assessment, Beijing 100022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianzhong","family":"Shen","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Veterinary Public Health and Safety, Department of Basic Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4238-9080","authenticated-orcid":false,"given":"Congming","family":"Wu","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Veterinary Public Health and Safety, Department of Basic Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4493-0619","authenticated-orcid":false,"given":"Fupin","family":"Hu","sequence":"additional","affiliation":[{"name":"Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5928-9377","authenticated-orcid":false,"given":"Yang","family":"Wang","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Veterinary Public Health and Safety, Department of Basic Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2024,8,16]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1080\/22221751.2020.1799721"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1186\/s44280-023-00009-9"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(17)30489-9"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(22)00275-4"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2022.1003783"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1080\/22221751.2020.1721334"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid2602.190594"},{"key":"e_1_3_4_8_2","first-page":"3317","article-title":"Carriage of bla\n                  KPC-2 by a virulence plasmid in hypervirulent Klebsiella pneumoniae","volume":"73","author":"Dong N.","year":"2018","unstructured":"N. Dong , Carriage of blaKPC-2 by a virulence plasmid in hypervirulent Klebsiella pneumoniae. J. Antimicrob. Chemother. 73, 3317\u20133321 (2018).","journal-title":"J. Antimicrob. 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A.","year":"2017","unstructured":"M. A. San , Fitness costs of plasmids: A limit to plasmid transmission. Microbiol. Spectr. 5, 1\u201312 (2017).","journal-title":"Microbiol. 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Wang , Peptide nucleic acid restores colistin susceptibility through modulation of mcr-1 expression in Escherichia coli. J. Antimicrob. Chemother. 75, 2059\u20132065 (2020).","journal-title":"J. Antimicrob. 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