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Identification of a target cell permissive factor required for contact-dependent growth inhibition (CDI)

Elie J Diner1, Christina M Beck, Julia S Webb

  • 1Department of Molecular, Cellular, and Developmental Biology, University of California at Santa Barbara, CA 93106, USA.

Genes & Development
|February 16, 2012
PubMed

Insights

Bacterial contact-dependent growth inhibition (CDI) relies on CdiA-CT toxins. We discovered that the enzyme CysK activates these toxins, enabling bacterial growth inhibition and revealing a new regulatory mechanism for CDI.

Area of Science:

  • Microbiology
  • Bacterial Toxinology
  • Molecular Biology

Background:

  • Bacterial contact-dependent growth inhibition (CDI) uses CdiB/CdiA two-partner secretion systems.
  • CdiA effectors deliver toxins (CdiA-CT) to target cells, while immunity proteins prevent self-toxicity.

Purpose of the Study:

  • Investigate the activation mechanism of CdiA-CT from uropathogenic Escherichia coli (UPEC536).
  • Determine the role of host factors in CdiA-CT activity and CDI.

Main Methods:

  • In vitro biochemical assays to test CdiA-CT nuclease activity.
  • Complex formation analysis between CdiA-CT and potential activators.
  • Bacterial growth inhibition assays in wild-type and mutant Escherichia coli strains.

Main Results:

  • UPEC536 CdiA-CT is a latent tRNase, inactive without a specific activator.
  • Purified CysK (O-acetylserine sulfhydrylase A) activates CdiA-CT, enabling tRNA cleavage.
  • CysK and CdiA-CT form a stable complex, mimicking CysK/CysE interactions.
  • CysK is essential for CdiA-CT-mediated growth inhibition; ΔcysK mutants are resistant.

Conclusions:

  • CysK acts as a crucial permissive factor for UPEC536 CdiA-CT activity.
  • CysK-mediated activation of CdiA-CT is required for bacterial growth inhibition during CDI.
  • This study uncovers a novel mechanism for regulating CDI efficacy through host enzyme interaction.

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