Utilization of CRISPR Interference To Validate MmpL3 as a Drug Target in Mycobacterium tuberculosis

Antimicrob Agents Chemother. 2019 Jul 25;63(8):e00629-19. doi: 10.1128/AAC.00629-19. Print 2019 Aug.

Abstract

There is an urgent need for novel therapeutics to treat Mycobacterium tuberculosis infections. Genetic strategies for validating novel targets are available, yet their time-consuming nature limits their utility. Here, using MmpL3 as a model target, we report on the application of mycobacterial CRISPR interference for the rapid validation of target essentiality and compound mode of action. This strategy has the potential to rapidly accelerate tuberculosis drug discovery.

Keywords: CRISPRi; molecular genetics; mycobacteria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antitubercular Agents / pharmacology
  • Bacterial Proteins / genetics*
  • Clustered Regularly Interspaced Short Palindromic Repeats / genetics*
  • Drug Delivery Systems / methods
  • Humans
  • Membrane Transport Proteins / genetics*
  • Mycobacterium tuberculosis / drug effects
  • Mycobacterium tuberculosis / genetics*
  • Tuberculosis / drug therapy
  • Tuberculosis / microbiology

Substances

  • Antitubercular Agents
  • Bacterial Proteins
  • Membrane Transport Proteins
  • MmpL3 protein, Mycobacterium tuberculosis