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Inteins as targets for potential antimycobacterial drugs

Henry Paulus1

  • 1Boston Biomedical Research Institute, Watertown, Massachusetts 02472-1753, USA. paulus@bbri.org

Frontiers in Bioscience : a Journal and Virtual Library
|September 6, 2003
PubMed

Insights

Inteins, which mediate protein splicing in microorganisms, are promising targets for new antimycobacterial drugs. Screening systems have been developed to identify inhibitors of intein activity in Mycobacterium tuberculosis.

Area of Science:

  • Microbiology
  • Biochemistry
  • Molecular Biology

Background:

  • Inteins are protein splicing elements found in microorganisms, often interrupting essential genes.
  • Mycobacteria, including Mycobacterium tuberculosis, possess inteins in critical DNA repair and replication proteins (RecA, DnaB).
  • Inteins are attractive targets for developing specific antimycobacterial agents due to their unique presence and essential function.

Purpose of the Study:

  • To review existing screening systems for detecting mutations or inhibitors of protein splicing.
  • To highlight the potential of inteins as specific targets for antimycobacterial drug development.

Main Methods:

  • Description of four developed screening systems for protein splicing inhibition.
  • Three systems utilize conditional toxicity assays based on intein insertion into toxic proteins, monitoring bacterial growth.
  • One system employs purified proteins and measures Green Fluorescent Protein formation.

Main Results:

  • Established screening systems allow for the detection of compounds interfering with protein splicing.
  • These assays can monitor inhibition through bacterial growth or fluorescent protein production.

Conclusions:

  • Inteins represent highly specific and promising targets for novel antimycobacterial therapies.
  • The reviewed screening systems provide tools for discovering inhibitors of intein-mediated protein splicing.

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