DOI: 10.1002/ame2.70101
Establishment of a biosafe murine model of skeletal tuberculosis using Mycobacterium smegmatis
Yewei Jia1
Yuhuai Guo1
Yusheng Yang2
Jie Zhang1
Ziyang Zhang1
Ying Qu1
Jiulin Tan1
Jie Shen1
Nathachit Limjunyawong3
Jianzhong Xu1
Zehua Zhang1
Fei Luo1
Ce Dou1
1.Department of Orthopaedics,Southwest Hospital,Third Military Medical University(Army Medical University),Chongqing,China2.Department of Orthopaedics,Southwest Hospital,Third Military Medical University(Army Medical University),Chongqing,China;Center of Research Excellence in Allergy& Immunology,Research Department,Faculty of Medicine Siriraj Hospital,Mahidol University,Bangkok,Thailand3.Center of Research Excellence in Allergy& Immunology,Research Department,Faculty of Medicine Siriraj Hospital,Mahidol University,Bangkok,Thailand
摘要：Background:Skeletal tuberculosis(TB)remains a persistent clinical and research chal-lenge due to its chronic course,osteolytic destruction,and the limitations of existing animal models,which often require high-level biosafety containment or fail to repli-cate human skeletal pathology.
Methods:This study developed a biosafe,accessible,and versatile murine model of skeletal TB using Mycobacterium smegmatis,a fast-growing,nonpathogenic myco-bacterial species with high genomic homology to Mycobacterium tuberculosis.Three infection routes—subperiosteal calvarial injection,intratibial injection,and intra-cardiac inoculation—were systematically evaluated for their ability to induce lo-calized versus disseminated bone infection under standard biosafety level(BSL)-1 conditions.
Results:Subperiosteal calvarial and intratibial injection of M.smegmatis induced local-ized bone lesions characterized by osteolysis,sequestrum formation,granulomatous inflammation,and increased osteoclast activity.Intratibial infection additionally trig-gered compartment-specific immune responses,including neutrophil and macrophage expansion,transient B-cell depletion,and activation of interferon-γ+(IFN-γ+)T cells,reflecting active immune remodeling at the infection site.Systemic dissemination via intracardiac injection reproducibly generated progressive vertebral and tibial bone destruction with organized granuloma formation and immune cell infiltration but without prominent sequestrum formation.Compared to intratibial infection,intracar-diac delivery exhibited lower intragroup variability and more closely recapitulated the diffuse progression of extrapulmonary skeletal tuberculosis.
Conclusions:This M.smegmatis-based murine model provides a straightforward,reliable,and immunopathologically relevant platform for exploring host-pathogen dynamics,immune-driven bone destruction,and early-stage therapeutic testing in skeletal TB,all within standard BSL-1 laboratories.This model fills a critical gap by enabling BSL-1 research into skeletal TB mechanisms and drug development.
机标关键词：modelbiosafeestablishmentmurinemycobacteriumskeletalsmegmatistuberculosis
论文发表日期：2026-01-30
在线出版日期：2026-03-27（本平台首次上网日期，不代表文献的发表时间）
页数：16( 5-20 )
英文信息