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Determinants of pH-dependent modulation of translocation in dermonecrotic G-protein-deamidating toxins

Tana L Repella1, Mengfei Ho, Brenda A Wilson

  • 1Department of Microbiology, School of Molecular and Cell Biology, University of Illinois atUrbana-Champaign, Urbana, IL 61801, USA. repella@illinois.edu

Toxins
|July 30, 2013
PubMed

Insights

Cytotoxic necrotizing factors (CNFs) and Pasteurella multocida toxin (PMT) share N-terminal similarities. This region modulates toxin responses to pH changes, influencing cellular intoxication and cargo delivery.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Toxicology

Background:

  • Cytotoxic necrotizing factors (CNFs) from E. coli and Yersinia, along with Pasteurella multocida toxin (PMT), possess similar N-terminal regions.
  • This conserved N-terminal domain is crucial for receptor binding and translocation, facilitating the delivery of catalytic effector domains into host cells.
  • Variations within this region may dictate specific cellular receptor interactions and target cell tropism.

Purpose of the Study:

  • To investigate the functional role of the conserved N-terminal region of CNFs and PMT.
  • To identify novel functions of this region beyond receptor binding and translocation.
  • To understand how this region influences toxin behavior under varying pH conditions during host cell intoxication.

Main Methods:

  • Comparative sequence analysis of CNFs and PMT N-terminal domains.
  • Utilizing cellular inhibitors to probe toxin-host interactions.
  • Investigating toxin activity and cargo delivery under different pH environments.

Main Results:

  • The N-terminal region of CNFs and PMT plays a role in modulating the toxins' response to pH.
  • This modulation impacts the intoxication process and the delivery efficiency of catalytic domains into the host cytosol.
  • A novel function for the N-terminal region in regulating pH-dependent responses was identified.

Conclusions:

  • The N-terminal region of CNFs and PMT is a multifunctional domain involved in pH-dependent modulation of toxin activity.
  • Understanding these pH-responsive mechanisms is critical for elucidating the pathogenesis of these bacterial toxins.
  • This finding opens new avenues for therapeutic strategies targeting toxin delivery and host cell manipulation.

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