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Quantification of Cytosolic vs. Vacuolar Salmonella in Primary Macrophages by Differential Permeabilization
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Salmonella typhi encodes a functional cytolethal distending toxin that is delivered into host cells by a

Erik Haghjoo1, Jorge E Galán

  • 1Section of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536, USA.

Proceedings of the National Academy of Sciences of the United States of America
|April 9, 2004
PubMed

Insights

Salmonella Typhi uses a novel cytolethal distending toxin (CDT) delivery mechanism. Bacterial internalization into host cells bypasses the need for typical CDT B subunits, enabling CdtB

Area of Science:

  • Microbiology
  • Bacterial Pathogenesis
  • Molecular Biology

Background:

  • Cytolethal distending toxin (CDT) is a bacterial toxin causing host cell cycle arrest via DNA damage.
  • CDT is typically composed of CdtA, CdtB (enzymatically active subunit), and CdtC subunits.
  • CdtA and CdtC facilitate the delivery of CdtB into host cells.

Purpose of the Study:

  • To investigate the CDT encoding and activity in Salmonella enterica serovar Typhi.
  • To elucidate the mechanism of CDT delivery in S. Typhi, particularly in the absence of CdtA and CdtC homologs.

Main Methods:

  • Functional analysis of CDT activity in S. Typhi.
  • Investigation of gene expression and protein function related to CDT.
  • Assessment of bacterial internalization and its effect on toxin activity.

Main Results:

  • S. Typhi encodes CDT activity dependent on a CdtB homologous protein.
  • S. Typhi lacks apparent homologs for CdtA and CdtC.
  • CDT toxicity and cdtB expression require bacterial internalization into host cells.

Conclusions:

  • S. Typhi utilizes a unique CDT delivery system.
  • Bacterial internalization into host cells circumvents the need for canonical CDT B subunits (CdtA/CdtC).
  • This mechanism represents a novel pathway for bacterial toxin delivery.

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