Game of ‘Somes: Protein Destruction for Mycobacterium tuberculosis Pathogenesis

The proteasome system of Mycobacterium tuberculosis is required for causing disease. Proteasomes are multisubunit chambered proteases and, until recently, were only known to participate in adenosine triphosphate (ATP)-dependent proteolysis in bacteria. In this review, we discuss the latest advances in understanding how both ATP-dependent and ATP-independent proteasome-regulated pathways contribute to M. tuberculosis virulence.

TrendsThe proteasome is a highly regulated protease that is required for the pathogenesis of Mycobacterium tuberculosis.Both ATP-dependent and ATP-independent pathways to the proteasome are needed to promote bacterial virulence.The M. tuberculosis proteasome degrades an enzyme that produces cytokinins, which break down into aldehydes that synergize with nitric oxide to kill bacteria.Defects in proteasomal degradation perturb metal homeostasis, including zinc- and copper-regulated genes required for pathogenesis.Proteasome function is required for a robust heat-shock response.