Killing in self-defense: proapoptotic drugs to eliminate intracellular pathogens

Abstract

Intracellular infections rely on host cell survival for replication and have evolved several mechanisms to prevent infected cells from dying. Drugs that promote apoptosis, a noninflammatory form of cell death, can dysregulate these survival mechanisms to kill infected cells via a mechanism that resists the evolution of drug resistance. Two such drug classes, known as SMAC mimetics and BH3 mimetics, have shown preclinical efficacy at mediating clearance of liver-stage malaria and chronic infections such as hepatitis-B virus and Mycobacterium tuberculosis. Emerging toxicity and efficacy data have reinforced the broad applicability of these drugs and form the foundations for preclinical and clinical studies into their various usage cases.