Targeting the Proteostasis Network for Mycobacterial Drug Discovery

Tania J. Lupoli, Julien Vaubourgeix, Kristin Burns-Huang, Ben Gold

Research output: Contribution to journalReview articlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)478-498
Number of pages21
JournalACS Infectious Diseases
Volume4
Issue number4
DOIs
StatePublished - Apr 13 2018

Keywords

  • Mycobacterium tuberculosis
  • antibiotics
  • chaperones
  • host immunity
  • proteases
  • proteasome
  • protein aggregation
  • protein folding
  • protein misfolding
  • proteolysis
  • proteostasis
  • proteostasis network

ASJC Scopus subject areas

  • Infectious Diseases

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