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The antibacterial threaded-lasso peptide capistruin inhibits bacterial RNA polymerase

Konstantin Kuznedelov1, Ekaterina Semenova, Thomas A Knappe

  • 1(1)Department of Biochemistry and Molecular Biology and Waksman Institute of Microbiology, Rutgers, the State University of New Jersey, Piscataway, NJ 08854, USA.

Journal of Molecular Biology
|March 15, 2011
PubMed

Insights

Capistruin, a peptide antibiotic, inhibits bacterial growth by targeting RNA polymerase (RNAP). This finding suggests RNAP is a common target for threaded-lasso peptides, broadening our understanding of antibacterial mechanisms.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Biochemistry

Background:

  • Capistruin is a novel threaded-lasso peptide antibiotic from Burkholderia thailandensis E264.
  • Its growth inhibition extends to Burkholderia and Pseudomonas species.
  • The specific molecular target of capistruin remained unidentified.

Purpose of the Study:

  • To identify the functional target of the antibiotic capistruin.
  • To investigate the mechanism of action of capistruin by comparing it to microcin J25 (MccJ25).
  • To determine if capistruin and MccJ25 share a common target.

Main Methods:

  • Comparative analysis of capistruin activity against wild-type and mutant Escherichia coli RNA polymerase (RNAP).
  • Testing capistruin efficacy on an E. coli strain engineered for MccJ25 resistance.
  • Utilizing genetic analysis to confirm the role of RNAP mutations in resistance.

Main Results:

  • Capistruin inhibited wild-type E. coli RNAP, similar to MccJ25.
  • Mutant E. coli RNAP, resistant to MccJ25, also showed resistance to capistruin.
  • A specific mutation in an RNAP subunit gene conferred resistance to both capistruin and MccJ25.

Conclusions:

  • The structural similarity between capistruin and MccJ25 reflects functional similarity.
  • Bacterial DNA-dependent RNA polymerase (RNAP) is the functional target of capistruin.
  • Bacterial RNAP is a likely target for other threaded-lasso peptides.

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