The Role of the Francisella Tularensis Pathogenicity Island in Type VI Secretion, Intracellular Survival, and Modulation of Host Cell Signaling

Abstract

Francisella tularensis is a highly virulent gram-negative intracellular bacterium that causes the zoonotic disease tularemia. Essential for its virulence is the ability to multiply within host cells, in particular monocytic cells. The bacterium has developed intricate means to subvert host immune mechanisms and thereby facilitate its intracellular survival by preventing phagolysosomal fusion followed by escape into the cytosol, where it multiplies. Moreover, it targets and manipulates numerous host cell signaling pathways, thereby ameliorating the otherwise bactericidal capacity. Many of the underlying molecular mechanisms still remain unknown but key elements, directly or indirectly responsible for many of the aforementioned mechanisms, rely on the expression of proteins encoded by the Francisella pathogenicity island (FPI), suggested to constitute a type VI secretion system. We here describe the current knowledge regarding the components of the FPI and the roles that have been ascribed to them.

IglE Is an Outer Membrane-Associated Lipoprotein Essential for Intracellular Survival and Murine Virulence of Type A Francisella tularensis

“…However, this model is not supported by all of the results obtained to date. For example, whereas both LVS iglI and iglG mutants showed essentially wild-type growth in J774 macrophages, only the iglG mutant was proficient for growth in peritoneal exudates and BMMs (22). Differences in intracellular replication and induction of host cell death pathways were also observed following infection of J774 macrophages with pdpC, iglC, iglG, or iglI mutants of LVS (56).…”

“…iglE is predicted to encode a lipoprotein on the basis of the presence of a putative signal peptidase II (SPII) cleavage site and a conserved cysteine residue at position 22 in the iglE-coding sequence. However, there are limited published data to substantiate this directly (22). To test this, we first analyzed the behavior of IglE in the nonionic detergent TX-114.…”

Repression of Inflammasome by Francisella tularensis during Early Stages of Infection

“…The virulence properties and mechanisms underlying innate immune subversion of F. tularensis are unique and remain largely undefined. F. tularensis lacks toxins or type III and IV secretion systems but possesses a type VI secretion system (9,10). Macrophages are the primary sites of predilection for F. tularensis.…”

Importance of PdpC, IglC, IglI, and IglG for Modulation of a Host Cell Death Pathway Induced by Francisella tularensis

“…tularensis and subsp. holarctica and in the live vaccine strain (17,18). The latter is an empirically attenuated strain of F. tularensis subsp.…”