Abstract
BackgroundA prerequisite for the virulence of the facultative intracellular bacterium Francisella tularensis is effective intramacrophage proliferation, which is preceded by phagosomal escape into the cytosol, and ultimately leads to host cell death. Many components essential for the intracellular life cycle are encoded by a gene cluster, the Francisella pathogenicity island (FPI), constituting a type VI secretion system.ResultsWe characterized the FPI mutant ΔpdpC of the live vaccine strain (LVS) of F. tularensis and found that it exhibited lack of intracellular replication, incomplete phagosomal escape, and marked attenuation in the mouse model, however, unlike a phagosomally contained FPI mutant, it triggered secretion of IL-1β, albeit lower than LVS, and markedly induced LDH release.ConclusionsThe phenotype of the ΔpdpC mutant appears to be unique compared to previously described F. tularensis FPI mutants.
Highlights
A prerequisite for the virulence of the facultative intracellular bacterium Francisella tularensis is effective intramacrophage proliferation, which is preceded by phagosomal escape into the cytosol, and leads to host cell death
Uptake of F. tularensis bacteria leads to rapid induction of a proinflammatory response, which is repressed upon bacterial internalization via modulation of host cell signaling and, again, execution of these mechanisms appears to require a cytosolic localization of bacteria [17,19,20,21,22]
Homologues exist in all species and subspecies of Francisella, they are not identical to PdpC of live vaccine strain (LVS)
Summary
A prerequisite for the virulence of the facultative intracellular bacterium Francisella tularensis is effective intramacrophage proliferation, which is preceded by phagosomal escape into the cytosol, and leads to host cell death. Many components essential for the intracellular life cycle are encoded by a gene cluster, the Francisella pathogenicity island (FPI), constituting a type VI secretion system. A lone member of one of these groups, and a phylogenetic outlier, is the T6SS of F. tularensis, a highly virulent Gram-negative intracellular pathogen, which causes the zoonotic disease tularemia in humans and many mammals [8]. Uptake of F. tularensis bacteria leads to rapid induction of a proinflammatory response, which is repressed upon bacterial internalization via modulation of host cell signaling and, again, execution of these mechanisms appears to require a cytosolic localization of bacteria [17,19,20,21,22]. Two notable exceptions are the ΔiglI and ΔiglG mutants of LVS, since these are avirulent but show intact growth in certain monocytic cells, with only marginal cytopathogenic effects [17]
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