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Type IV pili-mediated secretion modulates Francisella virulence

Anthony J Hager1, Diana L Bolton, Mark R Pelletier

  • 1Department of Pediatrics, Division of Infectious Diseases, University of Washington, Seattle, WA, USA.

Molecular Microbiology
|September 22, 2006
PubMed

Insights

Francisella novicida secretes PepO protease via a Type IV pilus system, which limits bacterial spread in mice. Loss of PepO function may explain the high virulence of human pathogenic Francisella strains.

Area of Science:

  • Microbiology
  • Infectious Diseases
  • Bacterial Pathogenesis

Background:

  • Francisella tularensis causes tularaemia, a zoonotic disease.
  • Francisella novicida is pathogenic in immunocompromised individuals and mice.
  • The Type IV pilus (T4P) secretion system's role in Francisella virulence is not fully understood.

Purpose of the Study:

  • To identify secreted proteins and the T4P secretion system in F. novicida.
  • To investigate the function of the secreted protease PepO in F. novicida pathogenesis.
  • To explore the implications of PepO function in the evolution of Francisella virulence.

Main Methods:

  • Proteomic and bioinformatic analyses to identify secreted proteins and the T4P system.
  • Gene transcription analysis regulated by the virulence regulator MglA.
  • Intradermal infection of mice to assess bacterial spread and host immune response.

Main Results:

  • Seven F. novicida secreted proteins, including PepO protease and BglX beta-glucosidase, were identified.
  • PepO and BglX transcription is regulated by MglA.
  • F. novicida mutants lacking T4P secretion or PepO showed enhanced systemic spread in mice.
  • PepO mutants increased neutrophil infiltration in mouse airways.
  • PepO, a zinc protease, is homologous to mammalian endothelin-converting enzyme ECE-1.

Conclusions:

  • Secretion of PepO limits F. novicida spread by inducing vasoconstriction.
  • Mutations in PepO in human pathogenic strains may contribute to their high virulence.
  • The T4P system and PepO are crucial for F. novicida pathogenesis.

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