How bacteria escape from digestion in the phagosome: comparative analysis of the Type 6 Secretion System in pathogenic Francisella and non-pathogenic Parafrancisella bacteria

The γ-proteobacterium Francisella includes numerous species (F. tularensis, F. noatunensis, F. orientalis, F. halioticida and others) which are highly pathogenic to humans, fishes and molluscs. These species cause diseases by entering the eukaryotic cell through phagocytosis, and rapidly escaping from the phagosome to multiply into the cytosol. Their ability to avoid phagosome digestion by the target cell is essentially due to a gene cluster known as Francisella pathogenicity island (or FPI), which contains genes encoding an atypical type VI secretion system (T6SS). Proteins encoded by the T6SS genes generate a needle-like structure which anchors to the bacterial membrane and is used to inject effector proteins into the target cell. We have analyzed the genomes of three strains of a non-pathogenic species of Francisella, recently re-named Parafrancisella adeliensis, that have been raised as cytoplasmic endosymbionts of cells of two Antarctic and Arctic species of the ciliate Euplotes (E. petzi and E. nobilii). All three genomes contain a new 23404-bp FPI-like gene cluster, in which the T6SS genes are associated with three other genes encoding effector proteins. Considering that in addition to being not pathogenic, P. adeliensis is unable to grow at 37 °C and easy to be cultivated, this identification strongly suggests to use the microbial Euplotes/Parafrancisella association as a new model to investigate the role of each T6SS component and the mechanism of bacterial invasion of eukaryotic cells.