Targeting the Proteostasis Network for Mycobacterial Drug Discovery

ACS Infectious Diseases
Tania J LupoliBen Gold

Abstract

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains one of the world's deadliest infectious diseases and urgently requires new antibiotics to treat drug-resistant strains and to decrease the duration of therapy. During infection, Mtb encounters numerous stresses associated with host immunity, including hypoxia, reactive oxygen and nitrogen species, mild acidity, nutrient starvation, and metal sequestration and intoxication. The Mtb proteostasis network, composed of chaperones, proteases, and a eukaryotic-like proteasome, provides protection from stresses and chemistries of host immunity by maintaining the integrity of the mycobacterial proteome. In this Review, we explore the proteostasis network as a noncanonical target for antibacterial drug discovery.

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Jan 4, 2019·Antimicrobial Agents and Chemotherapy·Mary P ChoulesSanghyun Cho
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Methods Mentioned

BETA
protein folding
protein
nucleotide exchange
nucleotide-exchange
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