Highlights
- •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.
Abstract
Objectives
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.
Methods
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.
Results
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.
Conclusion
M.tb alters its transcriptome to establish infection in bone by upregulating certain
virulence genes which play a key role in disturbing bone homeostasis.
Keywords
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Article info
Publication history
Published online: December 19, 2022
Accepted:
December 13,
2022
Identification
Copyright
© 2022 The British Infection Association. Published by Elsevier Ltd. All rights reserved.