Mycobacterium tuberculosis Rv0198c, a putative matrix metalloprotease is involved in pathogenicity

Area of Science:

• Microbiology
• Molecular Biology
• Pathogen Biology

Background:

• Proteases play vital roles in pathogen biology.
• Mycobacterium tuberculosis is a significant global human pathogen.
• The function of specific proteases, like Rv0198c, in M. tuberculosis remains largely uncharacterized.

Purpose of the Study:

• To investigate the role of the putative matrix metalloprotease Rv0198c in Mycobacterium tuberculosis.
• To determine the impact of Rv0198c deletion on M. tuberculosis growth, protease activity, gene expression, and virulence.

Main Methods:

• Construction of an unmarked chromosomal deletion mutant for Rv0198c.
• Analysis of bacterial growth in axenic culture.
• Measurement of overall protease activity in cell-free extracts.
• Transcriptome analysis (RNA sequencing) under aerobic growth conditions.
• Virulence assays in human macrophage-like THP-1 cells and mouse models (SCID and C57BL/6).

Main Results:

• No significant differences in axenic culture growth or overall protease activity were observed between the mutant and wild-type strains.
• Transcriptome analysis revealed differential gene expression, including upregulation of Rv2488c and Rv1971, and downregulation of qor (Rv1454c).
• The Rv0198c deletion mutant showed comparable replication in THP-1 cells but exhibited hyper-virulence in SCID and C57BL/6 mouse models.

Conclusions:

• Rv0198c is not essential for M. tuberculosis growth in vitro or overall protease activity.
• Rv0198c plays a significant role in modulating the virulence of Mycobacterium tuberculosis during infection.
• The deletion mutant's hyper-virulence phenotype in mouse models highlights Rv0198c's importance in the host-pathogen interaction.