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New publication on the role of ACOD1 in Brucella infection

In this article published in PLOS Pathogens, Aurore Demars from the group of Eric Muraille explores the role of aconitate decarboxylase 1 gene (Acod1; also known as Immune responsive gene 1) in the control of pulmonary Brucella infection in mouse. They observe that Acod1 is upregulated in murine alveolar macrophages in response to Brucella infection and that Acod1 deficient mice display a higher bacterial load in their lungs than control mice, demonstrating that Acod1 participates in the control of pulmonary Brucella infection. The ACOD1 enzyme is mostly produced in mitochondria of macrophages, and converts cis-aconitate, a metabolite in the Krebs cycle, into itaconate. This later has a dose-dependent inhibitory effect on Brucella growth in vitro but not on isocitrate lyase deletion mutant of Brucella. Structural analysis demonstrates the binding of itaconate into the binding site of Brucella isocitrate lyase. Collectively, these data suggest that bacterial isocitrate lyase might be a target of Acod1 in infected alveolar macrophage. As the mouse Acod1 enzyme is ∼80% identical in its amino acid sequence to the human Acod1, the development of pharmacological agents that enhance Acod1 function or promote itaconate production might help to control early stages of pulmonary Brucella infection.
September 16th 2021 - 14:36