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Anti-infectives

Stuck in a tunnel

Nature Reviews Microbiology volume 2, page 615 (2004)Cite this article

MccJ25 is a 21-amino-acid antibiotic with an unusual lariat (knot) structure. It inhibits Gram-negative bacteria by targeting the bacterial RNAP, which is a complex of five subunits (α2ββ′ω). Mutations conferring resistance to MccJ25 map to the gene that encodes the β′ subunit. The use of RNAP inhibitors, including antibiotics such as rifampicin, is an elegant tool for defining mechanisms of transcription. Now, groups led by Richard Ebright and Konstantin Severinov have used complementary approaches to address how MccJ25 inhibits RNAP.

Transcription in bacteria is a multi-step process; first, RNAP binds to promoter DNA and forms a closed complex; second, the DNA is locally unwound (melted), yielding an open complex; third, transcription is initiated, producing very short RNA fragments, less than 9–11 bp (called abortive initiation); and, finally, the RNAP is released to produce a full-length transcript. By incorporating MccJ25 into assays that assemble functional RNAP–DNA complexes both groups showed that the antibiotic does not inhibit the first two steps in this process — but specifically inhibited abortive initiation and elongation, and, moreover, adding excess NTPs overcame this inhibition.

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ORIGINAL RESEARCH PAPERS

  1. Mukhopadhyay, J. et al. Antibacterial peptide Microcin J25 inhibits transcription by binding within and obstructing the RNA polymerase secondary channel. Mol. Cell 14, 739–751 (2004)

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  2. Adelman, K. et al. Molecular mechanism of transcription inhibition by peptide antibiotic Microcin J25. Mol. Cell 14, 753–762 (2004)

    Article  CAS  Google Scholar 

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Authors
  1. Susan Jones
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Jones, S. Stuck in a tunnel. Nat Rev Microbiol 2, 615 (2004). https://doi.org/10.1038/nrmicro965

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  • DOI: https://doi.org/10.1038/nrmicro965

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