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Gram-negative bacteria utilize sophisticated protein secretion systems to transport proteins across their double-membrane envelope into the extracellular environment or host cells. Based on their mechanism of action, these systems are classified into one-step and two-step pathways.One-Step Secretion Systems (Types I, III, IV, and VI)One-step secretion systems bypass the periplasm entirely, forming a continuous channel that spans both the inner and outer membranes:Type I Secretion System (T1SS):...
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Escherichia coli Type III Secretion System 2 Is Associated With Patient Mortality in Bloodstream Infections.

Joshua T Thaden1, Phillip Cox1, Paa Kwesi Ankrah1

  • 1Division of Infectious Diseases.

The Journal of Infectious Diseases
|May 22, 2025
PubMed
Summary

Genomic islands in E. coli, ETT2 and ETT2-AR, are linked to increased patient mortality in bloodstream infections. These islands enhance bacterial virulence by resisting complement and promoting host cell adhesion and death.

Keywords:
Escherichia coliETT2bacteremiabloodstream infectiontype III secretion system

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Area of Science:

  • Microbiology
  • Genomics
  • Infectious Diseases

Background:

  • Escherichia coli possesses a large accessory genome, but its contribution to patient mortality remains unclear.
  • Understanding the genetic basis of E. coli virulence is crucial for improving patient outcomes.

Purpose of the Study:

  • To identify specific genomic features of E. coli associated with increased in-hospital mortality.
  • To investigate the functional mechanisms by which these genomic features contribute to bacterial virulence.

Main Methods:

  • Whole genome sequencing of 193 E. coli bloodstream infection isolates.
  • Pan-genome analysis to identify genomic islands linked to attributable mortality.
  • Serum growth assays and bacterial-host cell interaction assays to determine virulence mechanisms.

Main Results:

  • Two co-localized genomic islands, ETT2 and ETT2-AR, were associated with increased attributable mortality (OR 3.0, p=0.03).
  • These islands encode a type III secretion system (T3SS) homologous to ETT2 and ETT2-AR.
  • ETT2/ETT2-AR enhanced virulence by inhibiting complement activation and increasing host cell adhesion and death.

Conclusions:

  • Genomic islands ETT2 and ETT2-AR are homologous to a T3SS and are found in specific E. coli lineages.
  • These islands are significantly associated with increased mortality in E. coli bloodstream infections.
  • ETT2/ETT2-AR confer increased bacterial virulence via complement resistance and enhanced host cell interactions.