{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:22:54Z","timestamp":1785410574609,"version":"3.56.0"},"reference-count":42,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82472300"],"award-info":[{"award-number":["82472300"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82130065"],"award-info":[{"award-number":["82130065"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82372270"],"award-info":[{"award-number":["82372270"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82472300"],"award-info":[{"award-number":["82472300"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["82130065"],"award-info":[{"award-number":["82130065"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["82372270"],"award-info":[{"award-number":["82372270"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Capital\u2019s Funds for Health Improvement and Research","award":["CFH 2026-1Q-1081"],"award-info":[{"award-number":["CFH 2026-1Q-1081"]}]},{"name":"Beijing Hospitals Authority\u2019s Ascent Plan","award":["DFL20241301"],"award-info":[{"award-number":["DFL20241301"]}]},{"award":["DFL20241301"],"award-info":[{"award-number":["DFL20241301"]}],"id":[{"id":"https:\/\/ror.org\/02jwb5s28","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004826","name":"Beijing Natural Science Foundation","doi-asserted-by":"publisher","award":["7264238"],"award-info":[{"award-number":["7264238"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>This study aimed to use quantitative phosphoproteomics to explore phosphorylation characteristics in Klebsiella pneumoniae (Kpn)-induced liver abscess (KPLA) formation and liver injury. The Kpn strain LA-Kpn006 was phenotypically and genotypically characterized. A murine model of KPLA was established via intragastric inoculation. Phosphoproteomics and bioinformatic analyses were conducted to identify and quantify phosphosites and phosphoproteins. LA-Kpn006 displayed a hypermucoviscous phenotype, serotype K1, ST23 genotype, and harbored six major virulence genes. Inoculation induced liver colonization and typical histopathological abscess lesions. We quantified 3017 phosphoproteins covering 12,798 phosphosites (dominated by serine phosphorylation); 1723 proteins were upregulated and 425 downregulated. Bioinformatic analyses revealed remodeling in metabolism, stress response, signal transduction, and cytoskeleton organization. Upregulated proteins converged on fatty acid elongation, inositol phosphate metabolism, and the tricarboxylic acid cycle; downregulated proteins were enriched in PI3K\u2013Akt, IL-17 signaling, and T-cell differentiation. Protein\u2013protein interaction network analysis identified 10 key proteins (Src, Rac1, Actb, Hsp90aa1, Hsp90ab1, Egfr, Rps6, Pik3CA, Itgb1, and Fyn) that mediate inflammatory signaling, cytoskeleton remodeling, and immune infiltration. Dysregulated phosphorylation networks drive pathological metabolic adaptation, suppressed immune homeostasis, and cytoskeletal disorganization, collectively facilitating KPLA progression. The identified hub proteins and pathways represent high-value mechanistic targets and candidate therapeutic vulnerabilities for KPLA.<\/jats:p>","DOI":"10.3390\/pathogens15070739","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T03:06:52Z","timestamp":1784084812000},"page":"739","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Phosphorylation Modification Characteristics of Liver Injury-Related Proteins in Klebsiella pneumoniae Liver Abscess"],"prefix":"10.3390","volume":"15","author":[{"given":"Chao","family":"Yan","sequence":"first","affiliation":[{"name":"Department of Bacteriology, Capital Center for Children\u2019s Health, Capital Institute of Pediatrics, Capital Medical University, Beijing 100020, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuanfeng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Bacteriology, Capital Center for Children\u2019s Health, Capital Institute of Pediatrics, Capital Medical University, Beijing 100020, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujie","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Bacteriology, Capital Center for Children\u2019s Health, Capital Institute of Pediatrics, Capital Medical University, Beijing 100020, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Bacteriology, Capital Center for Children\u2019s Health, Capital Institute of Pediatrics, Capital Medical University, Beijing 100020, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Bacteriology, Capital Center for Children\u2019s Health, Capital Institute of Pediatrics, Capital Medical University, Beijing 100020, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Bacteriology, Capital Center for Children\u2019s Health, Capital Institute of Pediatrics, Capital Medical University, Beijing 100020, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Bacteriology, Capital Center for Children\u2019s Health, Capital Institute of Pediatrics, Capital Medical University, Beijing 100020, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"107399","DOI":"10.1016\/j.micpath.2025.107399","article-title":"Emerging Challenges in Klebsiella pneumoniae: Antimicrobial Resistance and Novel Approach","volume":"202","author":"Shah","year":"2025","journal-title":"Microb. Pathog."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.1001\/archinte.1986.00360220057011","article-title":"Klebsiella pneumoniae Liver Abscess Associated with Septic Endophthalmitis","volume":"146","author":"Liu","year":"1986","journal-title":"Arch. Intern. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1016\/j.jinf.2006.11.008","article-title":"Emerging Invasive Liver Abscess Caused by K1 Serotype Klebsiella pneumoniae in Korea","volume":"54","author":"Chung","year":"2007","journal-title":"J. Infect."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.3201\/eid1410.071254","article-title":"Pyogenic Liver Abscess as Endemic Disease, Taiwan","volume":"14","author":"Tsai","year":"2008","journal-title":"Emerg. Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"6115","DOI":"10.1128\/AAC.01127-16","article-title":"High Prevalence of Hypervirulent Klebsiella pneumoniae Infection in China: Geographic Distribution, Clinical Characteristics, and Antimicrobial Resistance","volume":"60","author":"Zhang","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"221","DOI":"10.3201\/eid2402.170957","article-title":"Hypervirulent Klebsiella pneumoniae in Cryptogenic Liver Abscesses, Paris, France","volume":"24","author":"Rossi","year":"2018","journal-title":"Emerg. Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.amjms.2015.12.018","article-title":"Klebsiella pneumoniae Liver Abscess: An Emerging Disease","volume":"351","author":"Fazili","year":"2016","journal-title":"Am. J. Med. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e0050824","DOI":"10.1128\/iai.00508-24","article-title":"Klebsiella pneumoniae Liver Abscesses: Pathogenesis, Treatment, and Ongoing Challenges","volume":"93","author":"Tabashsum","year":"2025","journal-title":"Infect. Immun."},{"key":"ref_9","first-page":"80","article-title":"Hypervirulent Klebsiella pneumoniae (hvKp): Overview, Epidemiology, and Laboratory Detection","volume":"10","author":"Endimiani","year":"2024","journal-title":"Pathog. Immun."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1086\/519262","article-title":"Klebsiella pneumoniae Genotype K1: An Emerging Pathogen That Causes Septic Ocular or Central Nervous System Complications from Pyogenic Liver Abscess","volume":"45","author":"Fang","year":"2007","journal-title":"Clin. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e01987","DOI":"10.1016\/j.idcr.2024.e01987","article-title":"Pyogenic Liver Abscess Caused by an Atypical Hypervirulent Klebsiella pneumoniae K1-ST23 in Mexico","volume":"36","year":"2024","journal-title":"IDCases"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e00001-19","DOI":"10.1128\/CMR.00001-19","article-title":"Hypervirulent Klebsiella pneumoniae","volume":"32","author":"Russo","year":"2019","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Nguyen, T.N.T., Howells, G., and Short, F.L. (2025). How Klebsiella pneumoniae Controls Its Virulence. PLoS Pathog., 21.","DOI":"10.1371\/journal.ppat.1013499"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"105331","DOI":"10.1016\/j.ebiom.2024.105331","article-title":"What Defines Hypervirulent Klebsiella pneumoniae?","volume":"108","author":"Stanton","year":"2024","journal-title":"EBioMedicine"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1128\/AAC.01123-10","article-title":"Experimental Phage Therapy in Treating Klebsiella pneumoniae-Mediated Liver Abscesses and Bacteremia in Mice","volume":"55","author":"Hung","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1016\/j.tem.2015.09.013","article-title":"Protein Phosphorylation: A Major Switch Mechanism for Metabolic Regulation","volume":"26","author":"Humphrey","year":"2015","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1007\/978-1-4939-3049-4_21","article-title":"From Phosphosites to Kinases","volume":"1355","author":"Munk","year":"2016","journal-title":"Methods Mol. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2329","DOI":"10.1038\/s41467-025-57453-x","article-title":"Salmonella Exploits LRRK2-Dependent Plasma Membrane Dynamics to Invade Host Cells","volume":"16","author":"Zhu","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2144","DOI":"10.1038\/s41564-024-01734-6","article-title":"Yersinia Infection Induces Glucose Depletion and AMPK-Dependent Inhibition of Pyroptosis in Mice","volume":"9","author":"Yang","year":"2024","journal-title":"Nat. Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"100991","DOI":"10.1016\/j.mcpro.2025.100991","article-title":"Proteomics and Phosphoproteomics Revealed Dysregulated Kinases and Potential Therapy for Liver Fibrosis","volume":"24","author":"Cheng","year":"2025","journal-title":"Mol. Cell Proteom."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1016\/j.jhep.2020.03.023","article-title":"MLKL-Dependent Signaling Regulates Autophagic Flux in a Murine Model of Non-Alcohol-Associated Fatty Liver and Steatohepatitis","volume":"73","author":"Wu","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s12941-018-0302-9","article-title":"Hypervirulent Klebsiella pneumoniae (Hypermucoviscous and Aerobactin Positive) Infection over 6 Years in the Elderly in China: Antimicrobial Resistance Patterns, Molecular Epidemiology and Risk Factor","volume":"18","author":"Liu","year":"2019","journal-title":"Ann. Clin. Microbiol. Antimicrob."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"867","DOI":"10.18388\/abp.2015_1148","article-title":"Klebsiella pneumoniae: Characteristics of Carbapenem Resistance and Virulence Factors","volume":"62","author":"Candan","year":"2015","journal-title":"Acta Biochim. Pol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1128\/IAI.01347-13","article-title":"TREM-1 Promotes Survival during Klebsiella pneumoniae Liver Abscess in Mice","volume":"82","author":"Lin","year":"2014","journal-title":"Infect. Immun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1097\/HEP.0000000000000611","article-title":"Bile Acid-Induced IRF3 Phosphorylation Mediates Cell Death, Inflammatory Responses, and Fibrosis in Cholestasis-Induced Liver and Kidney Injury via Regulation of ZBP1","volume":"79","author":"Zhuang","year":"2024","journal-title":"Hepatology"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Bezdicek, M., Jakubickova, M., Bitusikova, V., Holubova, E., Vitkova, H., Kocmanova, I., Vitkova, I., Zdrazilova Dubska, L., and Lengerova, M. (2026). Emergence and Genomic Characterization of Hypervirulent ST23\/K1 Klebsiella pneumoniae: Local Epidemiology and Global Context. Front. Microbiol., 17.","DOI":"10.3389\/fmicb.2026.1758288"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3155","DOI":"10.1002\/prot.23148","article-title":"Phosphorylation Alters Backbone Conformational Preferences of Serine and Threonine Peptides","volume":"79","author":"Kim","year":"2011","journal-title":"Proteins"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1146\/annurev.immunol.22.012703.104721","article-title":"Phosphoinositide 3-Kinase: Diverse Roles in Immune Cell Activation","volume":"22","author":"Deane","year":"2004","journal-title":"Annu. Rev. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2629132","DOI":"10.1080\/21505594.2026.2629132","article-title":"Gut Microbiota-Driven IL-17A Production by Hepatic \u0393\u03b4 T Cells Enhances Neutrophil Defense against Systemic Staphylococcus Aureus Infection","volume":"17","author":"Pan","year":"2026","journal-title":"Virulence"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"118364","DOI":"10.1016\/j.jep.2024.118364","article-title":"Wogonin Mitigates Acetaminophen-Induced Liver Injury in Mice through Inhibition of the PI3K\/AKT Signaling Pathway","volume":"332","author":"Zhao","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2164","DOI":"10.1002\/eji.202049119","article-title":"Evolved to Protect, Designed to Destroy: IL-17-Producing \u0393\u03b4 T Cells in Infection, Inflammation, and Cancer","volume":"51","author":"Agerholm","year":"2021","journal-title":"Eur. J. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1007\/s12038-017-9727-0","article-title":"Structure Function Relations in PDZ-Domain-Containing Proteins: Implications for Protein Networks in Cellular Signalling","volume":"43","author":"Manjunath","year":"2018","journal-title":"J. Biosci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/bs.ircmb.2018.05.013","article-title":"Emerging Themes in PDZ Domain Signaling: Structure, Function, and Inhibition","volume":"343","author":"Liu","year":"2019","journal-title":"Int. Rev. Cell Mol. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e202302489","DOI":"10.26508\/lsa.202302489","article-title":"FERM Domain-Containing Proteins Are Active Components of the Cell Nucleus","volume":"7","author":"Vilmos","year":"2024","journal-title":"Life Sci. Alliance"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4099","DOI":"10.1038\/s41467-021-24349-5","article-title":"Reduced Efficacy of a Src Kinase Inhibitor in Crowded Protein Solution","volume":"12","author":"Kasahara","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.virol.2021.02.008","article-title":"Virus-Induced Activation of the Rac1 Protein at the Site of Respiratory Syncytial Virus Assembly Is a Requirement for Virus Particle Assembly on Infected Cells","volume":"557","author":"Ravi","year":"2021","journal-title":"Virology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s43556-024-00176-0","article-title":"Understanding PI3K\/Akt\/mTOR Signaling in Squamous Cell Carcinoma: Mutated PIK3CA as an Example","volume":"5","author":"Zheng","year":"2024","journal-title":"Mol. Biomed."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"815","DOI":"10.2174\/1568026620666200303123102","article-title":"Review on Epidermal Growth Factor Receptor (EGFR) Structure, Signaling Pathways, Interactions, and Recent Updates of EGFR Inhibitors","volume":"20","author":"Sabbah","year":"2020","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"100215","DOI":"10.1016\/j.jvssci.2024.100215","article-title":"Recent Advances in Proteomic Analysis to Study Carotid Artery Plaques","volume":"5","author":"Meschia","year":"2024","journal-title":"JVS Vasc. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"dev192724","DOI":"10.1242\/dev.192724","article-title":"\u03921 Integrin Regulates Convergent Extension in Mouse Notogenesis, Ensures Notochord Integrity and the Morphogenesis of Vertebrae and Intervertebral Discs","volume":"147","author":"Guo","year":"2020","journal-title":"Development"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1038\/s41580-023-00640-9","article-title":"Structural and Functional Complexity of HSP90 in Cellular Homeostasis and Disease","volume":"24","author":"Chiosis","year":"2023","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2199","DOI":"10.1101\/gad.351605","article-title":"Ribosomal Protein S6 Phosphorylation Is a Determinant of Cell Size and Glucose Homeostasis","volume":"19","author":"Ruvinsky","year":"2005","journal-title":"Genes. Dev."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/15\/7\/739\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T09:35:16Z","timestamp":1784194516000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/15\/7\/739"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,14]]},"references-count":42,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["pathogens15070739"],"URL":"https:\/\/doi.org\/10.3390\/pathogens15070739","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,14]]}}}