Francisella requires dynamic type VI secretion system and ClpB to deliver effectors for phagosomal escape

Nat Commun. 2017 Jun 16;8:15853. doi: 10.1038/ncomms15853.

Abstract

Francisella tularensis is an intracellular pathogen that causes the fatal zoonotic disease tularaemia. Critical for its pathogenesis is the ability of the phagocytosed bacteria to escape into the cell cytosol. For this, the bacteria use a non-canonical type VI secretion system (T6SS) encoded on the Francisella pathogenicity island (FPI). Here we show that in F. novicida T6SS assembly initiates at the bacterial poles both in vitro and within infected macrophages. T6SS dynamics and function depends on the general purpose ClpB unfoldase, which specifically colocalizes with contracted sheaths and is required for their disassembly. T6SS assembly depends on iglF, iglG, iglI and iglJ, whereas pdpC, pdpD, pdpE and anmK are dispensable. Importantly, strains lacking pdpC and pdpD are unable to escape from phagosome, activate AIM2 inflammasome or cause disease in mice. This suggests that PdpC and PdpD are T6SS effectors involved in phagosome rupture.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / genetics
  • Bacterial Proteins / immunology
  • Bacterial Proteins / metabolism*
  • Endopeptidase Clp / genetics
  • Endopeptidase Clp / immunology
  • Endopeptidase Clp / metabolism*
  • Female
  • Francisella tularensis / genetics
  • Francisella tularensis / immunology
  • Francisella tularensis / metabolism*
  • Gene Expression Regulation, Bacterial
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Phagosomes / immunology*
  • Phagosomes / microbiology
  • Tularemia / immunology
  • Tularemia / microbiology*
  • Type VI Secretion Systems / genetics
  • Type VI Secretion Systems / immunology
  • Type VI Secretion Systems / metabolism*

Substances

  • Bacterial Proteins
  • Type VI Secretion Systems
  • Endopeptidase Clp