Mycobacterium tuberculosis manipulates host inflammation and lipid metabolism through the SET1-interacting protein Rv1075c
A growing body of literature supports a critical role for nucleomodulins, proteins that traffic to host cell nuclei and manipulate nuclear processes, in intracellular bacterial pathogenesis. Here, we identify the Mycobacterium tuberculosis (Mtb) secreted protein Rv1075c as a nucleomodulin that targets a histone modifying protein complex in macrophages. We report that {Delta}Rv1075c Mtb infection…
Recent research has uncovered a crucial protein in Mycobacterium tuberculosis (Mtb) that manipulates host inflammation and lipid metabolism processes. The study identifies the Mtb secreted protein Rv1075c as a nucleomodulin, a protein that interacts with a histone modifying protein complex in macrophages. When Mtb lacks Rv1075c, the transcriptional response to inflammation and lipid metabolism is weakened, and the formation of foamy macrophages in the lungs of infected mice is impaired.
Utilizing mass spectrometry, researchers discovered that Rv1075c interacts with components of the H3K4me3-depositing SET1 histone methyltransferase complex. This interaction is vital for Rv1075c's ability to localize within the nucleus. Furthermore, the absence of Rv1075c leads to an overstimulation of inflammatory genes in activated macrophages.
These findings suggest that Mtb manipulates the host's chromatin machinery, utilizing the SET1 complex to establish a conducive environment for its persistence within the host organism.
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