Abstract
Francisella tularensis is a highly-infectious bacterium that causes the rapid, and often lethal disease, tularemia. Many studies have been performed to identify and characterize the virulence factors that F. tularensis uses to infect a wide variety of hosts and host cell types, evade immune defenses, and induce severe disease and death. This review focuses on the virulence factors that are present in the F. tularensis envelope, including capsule, LPS, outer membrane, periplasm, inner membrane, secretion systems, and various molecules in each of aforementioned sub-compartments. Whereas, no single bacterial molecule or molecular complex single-handedly controls F. tularensis virulence, we review here how diverse bacterial systems work in conjunction to subvert the immune system, attach to and invade host cells, alter phagosome/lysosome maturation pathways, replicate in host cells without being detected, inhibit apoptosis, and induce host cell death for bacterial release and infection of adjacent cells. Given that the F. tularensis envelope is the outermost layer of the bacterium, we highlight herein how many of these molecules directly interact with the host to promote infection and disease. These and future envelope studies are important to advance our collective understanding of F. tularensis virulence mechanisms and offer targets for future vaccine development efforts.
Highlights
Francisella tularensis is a Gram-negative intracellular bacterium and the causative agent of the zoonotic disease tularemia (Carvalho et al, 2014)
These studies have provided a wealth of information about many previously unstudied F. tularensis hypothetical proteins and have revealed novel virulence strategies, major questions still remain about the true role of many of these putative virulence factors in Type A and Type B virulent strains
We focused on components of the F. tularensis envelope that have been reported to contribute to immune evasion, intracellular replication and survival, and mammalian virulence
Summary
Francisella tularensis is a Gram-negative intracellular bacterium and the causative agent of the zoonotic disease tularemia (Carvalho et al, 2014). Capsule production appears to be well-conserved among many F. tularensis strains, as a monoclonal antibody generated against Schu S4 capsular material cross-reacted with 14 different Type A and Type B isolates, including LVS, but did not react against LPS (Apicella et al, 2010). Whereas Schu S4 capsule was found to be composed of mannose and rhamnose, a LVS capsule-like complex was found to contain mannose, glucose, and galactose, indicating that capsular composition may differ between Type A and B species (Bandara et al, 2011) Together, these studies demonstrated that many F. tularensis strains express a polysaccharide capsule that it is identical to the O-antigen but lacks other LPS components. Only the FTL0708 mutant was found to be deficient in capsule production but not LPS, demonstrating that some genes
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