Research Article| Volume 86, ISSUE 2, P134-146, February 2023

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Metabolic switching and cell wall remodelling of Mycobacterium tuberculosis during bone tuberculosis

  • Author Footnotes
    1 Present Address: Division of Bone and Mineral Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States.
    Khushpreet Kaur
    1 Present Address: Division of Bone and Mineral Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States.
    Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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  • Author Footnotes
    2 These authors contributed equally to this work.
    Sumedha Sharma
    2 These authors contributed equally to this work.
    Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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  • Author Footnotes
    2 These authors contributed equally to this work.
    Sudhanshu Abhishek
    2 These authors contributed equally to this work.
    Department of Biochemistry and Molecular Biology, Uniformed Services University of the Health Sciences, Bethesda, MD, United States
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  • Prabhdeep Kaur
    Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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  • Uttam Chand Saini
    Department of Orthopaedics, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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  • Mandeep Singh Dhillon
    Department of Orthopaedics, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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  • Petros C. Karakousis
    Centers for Tuberculosis Research and Systems Approaches for Infectious Diseases, School of Medicine, Johns Hopkins University, Baltimore, MD, United States
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  • Indu Verma
    Corresponding author.
    Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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  • Author Footnotes
    1 Present Address: Division of Bone and Mineral Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States.
    2 These authors contributed equally to this work.
Published:December 19, 2022DOI:


      • M.tb adapts to host environments primarily by alterations in its transcriptome.
      • Remodelling of M.tb cell wall and metabolic pathways was seen in bone TB lesions.
      • M.tb virulence genes were upregulated in bone lesions and cell line model.
      • M.tb virulence proteins inhibit osteoblast differentiation, altering bone homeostasis.
      • Further studies on the role of these proteins in bone TB needed using M.tb mutants.



      Bone tuberculosis (TB) is the third most common types of extrapulmonary tuberculosis. It is critical to understand mycobacterial adaptive strategies within bone lesions to identify mycobacterial factors that may have role in disease pathogenesis.


      Whole genome microarray was used to characterize the in-vivo transcriptome of Mycobacterium tuberculosis (M.tb) within bone TB specimens. Mycobacterial virulent proteins were identified by bioinformatic software. An in vitro osteoblast cell line model was used to study the role of these proteins in bone TB pathogenesis.


      914 mycobacterial genes were significantly overexpressed and 1688 were repressed in bone TB specimens. Pathway analysis of differentially expressed genes demonstrated a non-replicative and hypometabolic state of M.tb, reinforcement of the mycobacterial cell wall and induction of DNA damage repair responses, suggesting possible survival strategies of M.tb within bone. Bioinformatics mining of microarray data led to identification of five virulence proteins. The genes encoding these proteins were also upregulated in the in vitro MC3T3 osteoblast cell line model of bone TB. Further, exposure of osteoblast cells to two of these virulence proteins (Rv1046c and Rv3663c) significantly inhibited osteoblast differentiation.


      M.tb alters its transcriptome to establish infection in bone by upregulating certain virulence genes which play a key role in disturbing bone homeostasis.


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