Identified virulence factors of Francisella: Secretion system
Related genes: dotU1;
Keywords: Secretion system;
Type VI secretion system;
Phylogenetic analysis of T6SSs lead to the classification of the F. tularensis T6SS as a unique subtype T6SSii. Representatives of T6SSi are widespread among Proteobacteria, whereas T6SSiii have so far been identified only in Bacteroidetes.
Out of the 13 proteins that define the core of prototypical T6SSs, the FPI lacks obvious homologues for at least 5 of them.
A TssM/IcmF family protein (PdpB) lacks the conserved Walker A box required to bind ATP and to provide energy to the secretion process.
Francisella VgrG protein is much smaller than prototypical VgrG proteins.
The atypical T6SS might be linked to its unique ability to target the eukaryotic phagosomal membrane.
IglA/IglB heterodimers assemble to form T6SS Sheaths.
IglG a novel PAAR-like protein located at the tip of the T6SS.
Putative model for Francisella T6SS (From: Rigard M, et al., 2016. Francisella tularensis IglG Belongs to a Novel Family of PAAR-Like T6SS Proteins and Harbors a Unique N-terminal Extension Required for Virulence. PLoS Pathog 12(9):e1005821.).
Allowing the bacteria to disrupt the phagosomal membrane and enter the cytosol for growth.
Effectors encoded within (pdpC, pdbD) and outside (OpiA, OpiB) the FPI cooperate to enhance the growth of Francisella in macrophages.
Nano FE, et al., 2007. The Francisella pathogenicity island. Ann N Y Acad Sci 1105:122-37.
Clemens DL, et al., 2015. Atomic structure of T6SS reveals interlaced array essential to function. Cell 160(5):940-51.
Rigard M, et al., 2016. Francisella tularensis IglG Belongs to a Novel Family of PAAR-Like T6SS Proteins and Harbors a Unique N-terminal Extension Required for Virulence. PLoS Pathog 12(9):e1005821.
Eshraghi A, et al., 2016. Secreted Effectors Encoded within and outside of the Francisella Pathogenicity Island Promote Intramacrophage Growth. Cell Host Microbe 20(5):573-583.
Brodmann M, et al., 2017. Francisella requires dynamic type VI secretion system and ClpB to deliver effectors for phagosomal escape. Nat Commun 8:15853.