SIRT7 induces cytoskeletal remodelling via RAC1 to enhance host resistance to Mtb
Mycobacterium tuberculosis (Mtb) secretes several virulence determinants that alter phagosome biogenesis, enabling its survival within the cell. Nevertheless, the mechanism underlying this process remains considerably obscure. Here, we have identified a novel regulatory mechanism whereby SIRT7 mediates Rac1 activation in cytoskeletal remodelling during Mtb infection. We found that SIRT7 are significantly decreased during Mtb infection in both mRNA and protein levels. SIRT7 deficiency impairs macrophage phagocytosis and bacteriacidal activity by disrupts actin cytoskeleton dynamics. In the murine TB model, the deficiency of Sirt7 had an adverse effect on the host's response to Mtb since it led to an increase in bacterial burden and inflammation in the lung. Conversely, the overexpression of Sirt7 impeded bacterial growth. Mechanistically, we have shown that SIRT7 limits Mtb infection by directly interacting with and activating RAC1. Therefore, we conclude that SIRT7 is responsible for driving cytoskeletal remodeling through RAC1, thus providing crucial insight into host response during Mtb infection and offering a potential target for tuberculosis treatment. Overall design: Total RNA was extracted from either uninfected or H37Rv-infected BMDMs of Sirt7+/+ or Sirt7-/- at 12 hours post-infection, using the mirVana Isolation Kit (Life Technologies). The quality of the RNA was confirmed using an Agilent Bioanalyzer, and only samples with an RNA integrity number >7 were processed. After library construction, library purification, library detection, and library quantification, FastQC was used for sequencing data quality control, and the data was then filtered by Cutadapt. Short reads were aligned using the Hisat2(v2.0.1) software, and gene expression was calculated by the FPKM (Fragments Per Kilo bases per Million reads) (20436464) method using the Htseq software(V0.6.1).