{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:24:45Z","timestamp":1759796685007,"version":"build-2065373602"},"reference-count":61,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T00:00:00Z","timestamp":1733788800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFB3804500"],"award-info":[{"award-number":["2022YFB3804500"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["52372276","2002391","82172455"],"award-info":[{"award-number":["52372276","2002391","82172455"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014137","name":"Shanghai Shenkang Hospital Development Center","doi-asserted-by":"publisher","award":["SHDC12021117"],"award-info":[{"award-number":["SHDC12021117"]}],"id":[{"id":"10.13039\/501100014137","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018625","name":"Science and Technology Innovation Plan Of Shanghai Science and Technology Commission","doi-asserted-by":"publisher","award":["22S31900200"],"award-info":[{"award-number":["22S31900200"]}],"id":[{"id":"10.13039\/501100018625","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Small colony variant (SCV) is strongly linked to antibiotic resistance and the persistence of osteomyelitis. However, the intrinsic phenotypic instability of SCV has hindered a thorough investigation of its pathogenic mechanisms. In this study, phenotypically stable SCV strains are successfully recovered from clinical specimens, characterized by elevated drug resistance and reduced immunogenicity. Multi\u2010omics analysis revealed that the acquired high drug resistance is associated with altered flux in the purine metabolism pathway, attributable to mutations in the hypoxanthine phosphoribosyltransferase (<jats:italic>hpt<\/jats:italic>) gene. Furthermore, this study innovatively discovered that lonidamine, an inhibitor of cellular energy metabolism, can effectively mitigate SCV resistance to \u03b2\u2010lactam antibiotics, thereby facilitating its eradication. The underlying mechanism involves the reprogramming of purine metabolism. Therefore, a co\u2010delivery system for lonidamine and oxacillin is constructed with amino\u2010modified dendritic mesoporous silica as a carrier, which showed high efficacy and safety in combating SCV both in vitro and in vivo experiments. Overall, this study elucidated the pathogenic mechanisms of a class of clinically isolated SCV isolates with <jats:italic>hpt<\/jats:italic> mutations and provided a paradigm for treating SCV\u2010associated osteomyelitis by reprogramming purine metabolism.<\/jats:p>","DOI":"10.1002\/advs.202410781","type":"journal-article","created":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T14:01:27Z","timestamp":1733839287000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Resensitizing \u03b2\u2010Lactams by Reprogramming Purine Metabolism in Small Colony Variant for Osteomyelitis Treatment"],"prefix":"10.1002","volume":"12","author":[{"given":"Tingwang","family":"Shi","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery Shanghai Institute of Microsurgery on Extremities Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  600 Yishan Road Shanghai 200233 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiong","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  600 Yishan Road Shanghai 200233 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zesong","family":"Ruan","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Shanghai Institute of Microsurgery on Extremities Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  600 Yishan Road Shanghai 200233 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiyuan","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Shanghai Institute of Microsurgery on Extremities Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  600 Yishan Road Shanghai 200233 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenbo","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Shanghai Institute of Microsurgery on Extremities Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  600 Yishan Road Shanghai 200233 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhao","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Shanghai Institute of Microsurgery on Extremities Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  600 Yishan Road Shanghai 200233 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yihong","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Shanghai Institute of Microsurgery on Extremities Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  600 Yishan Road Shanghai 200233 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Shanghai Institute of Microsurgery on Extremities Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  600 Yishan Road Shanghai 200233 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guangyu","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Spine Lab The First Affiliated Hospital Zhejiang University School of Medicine  Hangzhou 310003 China"},{"name":"Joslin\u2010Beth Israel Deaconess Foot Center and The Rongxiang Xu MD Center for Regenerative Therapeutics Beth Israel Deaconess Medical Center Harvard Medical School  Boston MA 02215 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han","family":"Lin","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Ceramics Chinese Academy of Sciences Research Unit of Nanocatalytic Medicine in Specific Therapy for Serious Disease Chinese Academy of Medical Sciences  Shanghai 200050 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6106-2721","authenticated-orcid":false,"given":"Min","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Electrical and Electronic Engineering The University of Hong Kong  Pokfulam Road Hong Kong 999077 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1612-5794","authenticated-orcid":false,"given":"Yunfeng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Shanghai Institute of Microsurgery on Extremities Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  600 Yishan Road Shanghai 200233 China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,12,10]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-018-0019-y"},{"key":"e_1_2_9_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41413-022-00228-7"},{"key":"e_1_2_9_1_3","doi-asserted-by":"publisher","DOI":"10.1002\/EXP.20230087"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-022-00686-0"},{"key":"e_1_2_9_2_2","doi-asserted-by":"publisher","DOI":"10.1186\/s10020-023-00632-7"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1302\/0301-620X.104B5.BJJ-2021-1759.R1"},{"key":"e_1_2_9_3_2","doi-asserted-by":"publisher","DOI":"10.1302\/2046-3758.1112.BJR-2021-0590.R1"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1384"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkw060"},{"key":"e_1_2_9_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkv371"},{"key":"e_1_2_9_5_3","doi-asserted-by":"publisher","DOI":"10.1111\/all.13580"},{"key":"e_1_2_9_5_4","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2020.00321"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/emmm.201000115"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01178-17"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.1.5219.124-a"},{"key":"e_1_2_9_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01000-13"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00084-09"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.2106\/JBJS.21.00958"},{"key":"e_1_2_9_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-019-0597-0"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2017.12.006"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abj0716"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02081-21"},{"key":"e_1_2_9_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aal3011"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.02478-22"},{"key":"e_1_2_9_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00324-21"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2014.00099"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01775-14"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1TB02615A"},{"key":"e_1_2_9_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202310320"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00347"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202304774"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13954"},{"key":"e_1_2_9_20_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002497"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00187.2010"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.1c11132"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.01121"},{"key":"e_1_2_9_23_2","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aaf7279"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2017.09.003"},{"key":"e_1_2_9_24_2","doi-asserted-by":"publisher","DOI":"10.1099\/mgen.0.000623"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2012.09.016"},{"key":"e_1_2_9_26_1","doi-asserted-by":"crossref","DOI":"10.1128\/spectrum.01898-22","volume":"11","author":"Liu S.","year":"2023","journal-title":"Microbiol. Spectr."},{"key":"e_1_2_9_26_2","doi-asserted-by":"publisher","DOI":"10.1086\/507633"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202104079"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202305316"},{"key":"e_1_2_9_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-10042-1"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.40.8.1914"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002217"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-micro-020518-115943"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.11.017"},{"key":"e_1_2_9_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.01.021"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201489209"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jot.2019.07.006"},{"key":"e_1_2_9_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2017.11.009"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2015.12.012"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-00424-8"},{"key":"e_1_2_9_36_2","doi-asserted-by":"publisher","DOI":"10.1002\/EXP.20230054"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1039\/C5CP00552C"},{"volume-title":"Trends in Endocrinology and Metabolism","year":"2024","author":"Rong S.","key":"e_1_2_9_38_1"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.118.301062"},{"key":"e_1_2_9_39_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells8010067"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202306964"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202410781","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T09:03:00Z","timestamp":1759741380000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202410781"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,10]]},"references-count":61,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["10.1002\/advs.202410781"],"URL":"https:\/\/doi.org\/10.1002\/advs.202410781","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"type":"print","value":"2198-3844"},{"type":"electronic","value":"2198-3844"}],"subject":[],"published":{"date-parts":[[2024,12,10]]},"assertion":[{"value":"2024-09-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2410781"}}