SIRT2 inhibition enhances mitochondrial apoptosis in Brucella-infected bovine placental trophoblast cells.

Brucella is a successful pathogen that employs a plethora of immune evasion mechanisms. This contributes to pathogenesis and persistence and limits the efficacy of available treatments. An increasing understanding of host‒pathogen interactions suggests that integrating host-directed strategies with existing anti-Brucella treatments could lead to more effective bacterial clearance and a reduction in drug-resistant strains. SIRT2 is a nicotinamide adenine dinucleotide (NAD⁺)-dependent deacetylase found in mammals. It can deacetylate various transcription factors and regulatory proteins, playing crucial roles in host‒pathogen interactions and pathogen infection-induced apoptosis. In this study, we investigated the role of SIRT2 in Brucella-induced cell apoptosis using bovine placental trophoblast cells. Our results indicate that B. abortus A19 infection upregulates SIRT2 protein expression and significantly induces mitochondrial apoptosis in these cells. Furthermore, inhibition of SIRT2 exacerbates B. abortus A19-induced mitochondrial apoptosis and markedly inhibits intracellular bacterial survival. These results prove the role of SIRT2 in Brucella pathogenesis and the mechanism of action.