Mycobacterial metallophosphatase MmpE acts as a nucleomodulin to regulate host gene expression and promote intracellular survival - PubMed
5 hours ago
- #Mycobacterium tuberculosis
- #Nucleomodulin
- #Immune evasion
- Mycobacterium tuberculosis causes tuberculosis and remains a major global health challenge.
- Nucleomodulins are bacterial effectors targeting host cell nuclei, playing key roles in virulence.
- Rv2577 (MmpE) is identified as a Fe³+/Zn²+-dependent metallophosphatase and nucleomodulin.
- MmpE enters the host nucleus using nuclear localization signals RRR20-22 and RRK460-462.
- MmpE binds to the vitamin D receptor (VDR) gene promoter, inhibiting inflammatory gene expression.
- MmpE regulates the PI3K-Akt-mTOR pathway, arresting lysosome maturation to suppress immune responses.
- These mechanisms promote mycobacterial survival in macrophages and mice.
- MmpE is a conserved nucleomodulin in mycobacteria, revealing a novel intracellular survival strategy.