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Insights into the Stress Response Triggered by Kasugamycin in Escherichia coli

Christian Müller1, Lena Sokol2, Oliver Vesper3

  • 1Max F. Perutz Laboratories, Center for Molecular Biology, Department of Microbiology, Immunobiology and Genetics, University of Vienna, Vienna Biocenter (VBC), Dr. Bohr-Gasse 9/4, A-1030 Vienna, Austria. christian_mueller@univie.ac.at.

Antibiotics (Basel, Switzerland)
|June 4, 2016
PubMed

Insights

Kasugamycin antibiotic selectively synthesizes proteins by promoting protein-depleted ribosomes that translate leaderless mRNAs. This occurs through altered ribosome modification and distinct mRNA generation mechanisms.

Area of Science:

  • Molecular Biology
  • Microbiology
  • Genetics

Background:

  • Kasugamycin is a bacteriostatic antibiotic that inhibits protein synthesis by targeting the ribosome's mRNA track.
  • It specifically blocks translation initiation on canonical mRNAs but not on leaderless mRNAs.
  • Previous work showed kasugamycin induces protein-depleted ribosomes selective for leaderless mRNAs in E. coli.

Purpose of the Study:

  • To investigate the mechanisms behind selective protein synthesis during prolonged kasugamycin treatment.
  • To explore the generation of leaderless and short-leadered mRNAs.
  • To examine ribosome heterogeneity in response to kasugamycin.

Main Methods:

  • Bacterial culture and treatment with kasugamycin.
  • Analysis of mRNA populations (leaderless, short-leadered, canonical).
  • Ribosome profiling and characterization of ribosome composition and modification status.

Main Results:

  • Prolonged kasugamycin treatment leads to the selective synthesis of specific proteins.
  • Leaderless and short-leadered mRNAs are generated via distinct mechanisms, including alternative transcription and RNA processing.
  • Evidence of ribosome heterogeneity was observed, linked to altered modification of stalk proteins (bL7/L12).

Conclusions:

  • Kasugamycin induces selective protein synthesis by altering ribosome populations and mRNA accessibility.
  • The generation of specific mRNA types and ribosome heterogeneity are key responses to kasugamycin.
  • Ribosome stalk protein modification plays a role in kasugamycin-induced translational control.
Keywords:
Escherichia colikasugamycinleaderless mRNAtranslation initiation

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