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Orphan toxin OrtT (YdcX) of Escherichia coli reduces growth during the stringent response

Sabina Islam1, Michael J Benedik2, Thomas K Wood3

  • 1Department of Chemical Engineering, the Pennsylvania State University, University Park, PA 16802-4400, USA. sui112@psu.edu.

Toxins
|February 3, 2015
PubMed

Insights

This study identifies OrtT as an independent bacterial toxin that damages cell membranes. OrtT functions alone, without an antitoxin, to inhibit growth under specific antimicrobial stress conditions.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Bacterial Toxin Research

Background:

  • Toxin/antitoxin (TA) systems are common in prokaryotes, with toxins typically inactivated by antitoxins.
  • The existence and physiological relevance of toxins functioning without antitoxins (orphan toxins) remain largely unexplored.

Purpose of the Study:

  • To investigate whether orphan toxins are physiologically relevant.
  • To characterize the function and mechanism of the orphan toxin OrtT (formerly YdcX).

Main Methods:

  • Homologous protein analysis of the Escherichia coli GhoT/GhoS type V TA system.
  • Genetic screening to identify potential antitoxin partners.
  • Transmission electron microscopy to assess membrane damage.
  • Growth assays in the presence of antimicrobials (trimethoprim and sulfamethoxazole).

Main Results:

  • YdcX, renamed OrtT, was identified as a toxic protein lacking a corresponding antitoxin.
  • OrtT functions independently, not being inactivated by known antitoxins or regulatory RNAs.
  • OrtT causes membrane damage, leading to cell lysis and reduced growth.
  • OrtT's toxicity is exacerbated under conditions that induce the stringent response, specifically during inhibition of tetrahydrofolate synthesis.

Conclusions:

  • OrtT represents a novel class of independent bacterial toxins.
  • Orphan toxins can be physiologically relevant and contribute to cellular stress responses.
  • OrtT's mechanism involves membrane damage and impacts bacterial growth during specific antimicrobial treatments.

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