Genomics

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SIRT7 induces cytoskeletal remodelling via RAC1 to enhance host resistance to Mtb


ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE245205 | GEO | 2023/12/20

REPOSITORIES: GEO

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