{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T06:29:01Z","timestamp":1792045741812,"version":"4.4.0"},"reference-count":54,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T00:00:00Z","timestamp":1756771200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T00:00:00Z","timestamp":1756771200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["INV-030705"],"award-info":[{"award-number":["INV-030705"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2025,9,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Klebsiella pneumoniae<\/jats:italic>\n                      is a major cause of neonatal sepsis in low- to middle-income countries. With the proportion of multidrug-resistant\n                      <jats:italic toggle=\"yes\">K. pneumoniae<\/jats:italic>\n                      strains increasing globally and the lack of novel antibiotics in the pipeline, vaccination to prevent infections due to\n                      <jats:italic toggle=\"yes\">K. pneumoniae<\/jats:italic>\n                      is an alternative strategy to antibiotics. Several\n                      <jats:italic toggle=\"yes\">K. pneumoniae<\/jats:italic>\n                      vaccines are currently in development; however, there are no small animal models of\n                      <jats:italic toggle=\"yes\">K. pneumoniae<\/jats:italic>\n                      -associated neonatal sepsis that can be used to evaluate vaccine efficacy. Therefore, we developed and characterized a neonatal murine model of\n                      <jats:italic toggle=\"yes\">K. pneumoniae<\/jats:italic>\n                      infection. We found that neonatal C57BL\/6 mice were highly susceptible to\n                      <jats:italic toggle=\"yes\">K. pneumoniae<\/jats:italic>\n                      B5055, a serotype O1:K2 hypervirulent strain, via peroral inoculation, and the susceptibility of mice to\n                      <jats:italic toggle=\"yes\">K. pneumoniae<\/jats:italic>\n                      infection was age and dose dependent. Mice aged 2\u20133 days consistently exhibited 88%\u2013100% mortality when infected with 10\n                      <jats:sup>8<\/jats:sup>\n                      \u201310\n                      <jats:sup>9<\/jats:sup>\n                      colony-forming units of\n                      <jats:italic toggle=\"yes\">K. pneumoniae<\/jats:italic>\n                      B5055. This susceptibility progressively decreased during the neonatal period such that\n                      <jats:italic toggle=\"yes\">K. pneumoniae<\/jats:italic>\n                      B5055 at this dose was avirulent in 10-day-old and older C57BL\/6 mice following peroral administration. Two-day-old mice were bacteremic as early as 2 h post-infection, which was accompanied by systemic dissemination of\n                      <jats:italic toggle=\"yes\">K. pneumoniae<\/jats:italic>\n                      beyond the gastrointestinal tract into the brain, liver, lungs, and spleen. However, only the liver and lungs displayed inflammatory infiltrate around the portal tract and neutrophilic exudate in the alveoli and air spaces, when compared to uninfected mice, which showed no pathological effects. Collectively, these results show that we have generated a novel and reproducible animal model for\n                      <jats:italic toggle=\"yes\">K. pneumoniae<\/jats:italic>\n                      neonatal sepsis.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        The development of appropriate vaccines for\n                        <jats:italic toggle=\"yes\">K. pneumoniae<\/jats:italic>\n                        relies on suitable animal models for\n                        <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                        efficacy testing. However, to date, there are no small animal models of\n                        <jats:italic toggle=\"yes\">K. pneumoniae<\/jats:italic>\n                        -associated neonatal sepsis. We have established a neonatal mouse model of lethal\n                        <jats:italic toggle=\"yes\">K. pneumoniae<\/jats:italic>\n                        infection that is age dependent and mimics the heightened susceptibility to\n                        <jats:italic toggle=\"yes\">Klebsiella<\/jats:italic>\n                        spp. observed in human neonates. This newly discovered mouse model represents a valuable tool to study the pathogenesis of invasive\n                        <jats:italic toggle=\"yes\">K. pneumoniae<\/jats:italic>\n                        infections in the neonate and to develop novel vaccines aimed at minimizing morbidity and mortality associated with\n                        <jats:italic toggle=\"yes\">K. pneumoniae<\/jats:italic>\n                        neonatal sepsis.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.00697-25","type":"journal-article","created":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T13:00:07Z","timestamp":1754053207000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Development of a mouse model for\n                    <i>Klebsiella pneumoniae<\/i>\n                    -associated neonatal sepsis"],"prefix":"10.1128","volume":"13","author":[{"given":"Jernelle C.","family":"Miller","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04rq5mt64","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Vaccine Development and Global Health, University of Maryland School of Medicine","place":["Baltimore, USA"]},{"id":[{"id":"https:\/\/ror.org\/04rq5mt64","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, University of Maryland School of Medicine","place":["Baltimore, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myeongjin","family":"Choi","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04rq5mt64","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Vaccine Development and Global Health, University of Maryland School of Medicine","place":["Baltimore, USA"]},{"id":[{"id":"https:\/\/ror.org\/04rq5mt64","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, University of Maryland School of Medicine","place":["Baltimore, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyong","family":"Zhao","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04rq5mt64","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Vaccine Development and Global Health, University of Maryland School of Medicine","place":["Baltimore, USA"]},{"id":[{"id":"https:\/\/ror.org\/04rq5mt64","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, University of Maryland School of Medicine","place":["Baltimore, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ember M.","family":"Mushrush","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04rq5mt64","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Vaccine Development and Global Health, University of Maryland School of Medicine","place":["Baltimore, USA"]},{"id":[{"id":"https:\/\/ror.org\/04rq5mt64","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, University of Maryland School of Medicine","place":["Baltimore, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teklu B.","family":"Legesse","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00sde4n60","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathology, University of Maryland Medical Center","place":["Baltimore, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4362-9936","authenticated-orcid":true,"given":"Alan S.","family":"Cross","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04rq5mt64","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Vaccine Development and Global Health, University of Maryland School of Medicine","place":["Baltimore, USA"]},{"id":[{"id":"https:\/\/ror.org\/04rq5mt64","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, University of Maryland School of Medicine","place":["Baltimore, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2771-1609","authenticated-orcid":true,"given":"Scott M.","family":"Baliban","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04rq5mt64","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Vaccine Development and Global Health, University of Maryland School of Medicine","place":["Baltimore, USA"]},{"id":[{"id":"https:\/\/ror.org\/04rq5mt64","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, University of Maryland School of Medicine","place":["Baltimore, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0651-5748","authenticated-orcid":true,"given":"Sharon M.","family":"Tennant","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04rq5mt64","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Vaccine Development and Global Health, University of Maryland School of Medicine","place":["Baltimore, USA"]},{"id":[{"id":"https:\/\/ror.org\/04rq5mt64","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, University of Maryland School of Medicine","place":["Baltimore, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.04121-22"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.00078-15"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2020.01249"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2017.01576"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2023.1184205"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00031-13"},{"key":"e_1_3_5_8_2","volume-title":"Neonatal sepsis","author":"Singh M","year":"2024","unstructured":"Singh M, Alsaleem M, Gray CP. 2024. Neonatal sepsis. StatPearls Publishing, Treasure Island, FL."},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1097\/MOP.0000000000000315"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(19)30414-1"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1004239"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1004179"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-021-00870-7"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(20)30205-9"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.k5314"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(21)00050-5"},{"key":"e_1_3_5_17_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. Available from: https:\/\/www.who.int\/publications\/i\/item\/9789240093461. Retrieved 17 Feb 2025."},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40121-021-00533-4"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micres.2024.127837"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines12101177"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.3389\/fpubh.2023.1139832"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pedneo.2015.09.007"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0032-1333412"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.m3672"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2024.1367422"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2008.07.100"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0203143"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.00045-21"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1080\/14767058.2016.1265932"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiz062"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.3791\/52018"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-46775-x"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.1086\/319297"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1177\/03000605211021733"},{"key":"e_1_3_5_35_2","article-title":"Insight into neonatal sepsis: an overview","volume":"15","author":"Mahmoud HAH","year":"2023","unstructured":"MahmoudHAH, ParekhR, DhandibhotlaS, SaiT, PradhanA, AlugulaS, Cevallos-CuevaM, HayesBK, AthantiS, AbdinZ. 2023. Insight into neonatal sepsis: an overview. Cureus 15:e45530.","journal-title":"Cureus"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-022-04374-2"},{"key":"e_1_3_5_37_2","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2022.847827"},{"key":"e_1_3_5_38_2","doi-asserted-by":"publisher","DOI":"10.1164\/arrd.1983.128.4.662"},{"key":"e_1_3_5_39_2","volume-title":"Klebsiella pneumonia","author":"Ashurst JV","year":"2024","unstructured":"Ashurst JV, Dawson A. 2024. Klebsiella pneumonia. StatPearls Publishing, Treasure Island, FL."},{"key":"e_1_3_5_40_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.50468"},{"key":"e_1_3_5_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00071-20"},{"key":"e_1_3_5_42_2","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0000000000001403"},{"key":"e_1_3_5_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhin.2017.12.024"},{"key":"e_1_3_5_44_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2022.873253"},{"key":"e_1_3_5_45_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adg5562"},{"key":"e_1_3_5_46_2","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.00500-21"},{"key":"e_1_3_5_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2666-5247(23)00290-2"},{"key":"e_1_3_5_48_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00902-12"},{"key":"e_1_3_5_49_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-018-2222-7"},{"key":"e_1_3_5_50_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.01754"},{"key":"e_1_3_5_51_2","doi-asserted-by":"publisher","DOI":"10.1177\/2058738420950586"},{"key":"e_1_3_5_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(12)70205-0"},{"key":"e_1_3_5_53_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00001-19"},{"key":"e_1_3_5_54_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1501049112"},{"key":"e_1_3_5_55_2","doi-asserted-by":"publisher","DOI":"10.1128\/cdli.4.5.550-555.1997"}],"container-title":["Microbiology Spectrum"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/spectrum.00697-25","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/spectrum.00697-25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T13:04:07Z","timestamp":1756818247000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/spectrum.00697-25"}},"subtitle":[],"editor":[{"given":"Nagendran","family":"Tharmalingam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,9,2]]},"references-count":54,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,9,2]]}},"alternative-id":["10.1128\/spectrum.00697-25"],"URL":"https:\/\/doi.org\/10.1128\/spectrum.00697-25","relation":{},"ISSN":["2165-0497"],"issn-type":[{"value":"2165-0497","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,2]]},"assertion":[{"value":"2025-03-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00697-25"}}