Rv0687 a Putative Short-Chain Dehydrogenase Is Required for In Vitro and In Vivo Survival of Mycobacterium...

Area of Science:

• Microbiology
• Immunology
• Pathogenesis

Background:

• Mycobacterium tuberculosis (Mtb) is a human pathogen that survives within host cells.
• Mtb employs evasion mechanisms, including detoxifying enzymes like short-chain dehydrogenases/reductases (SDRs), to counter host-induced stress.

Purpose of the Study:

• To investigate the functional role of Rv0687, an SDR family gene, in Mtb pathogenesis.
• To assess the impact of Rv0687 deletion on Mtb's stress response and survival in host models.

Main Methods:

• Generated a Rv0687 deletion mutant (RvΔ0687) and complemented strain of Mtb.
• Evaluated in vitro stress responses (oxidative, nitrosative) of WT and RvΔ0687 strains.
• Assessed Mtb survival in macrophages and infection models using WT, RvΔ0687, and complemented strains in mice (Rag-/-, C57BL/6).

Main Results:

• RvΔ0687 exhibited increased sensitivity to oxidative and nitrosative stress agents.
• Deletion of Rv0687 compromised Mtb survival in macrophages and increased pro-inflammatory cytokine release (TNF-α, MIP-1α).
• RvΔ0687 showed reduced growth in spleen of Rag-/- mice and decreased bacterial burden in spleen and lungs of C57BL/6 mice, leading to longer survival in Rag-/- mice.

Conclusions:

• Rv0687 is crucial for Mtb's ability to withstand host-generated stress.
• The Rv0687 gene contributes to Mtb pathogenesis by promoting survival and virulence within the host.
• Targeting Rv0687 may represent a potential strategy for controlling Mtb infections.