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The Francisella tularensis Polysaccharides: What Is the Real Capsule?

Francisella tularensis is a tier 1 select agent responsible for tularemia in humans and a wide variety of animal species. Extensive research into understanding the virulence factors of the bacterium has been ongoing to develop an efficacious vaccine. At least two such virulence factors are described as capsules of F. tularensis: the O-antigen capsule and the capsule-like complex (CLC). These two separate entities aid in avoiding host immune defenses but have not been clearly differentiated. SUMMARY Francisella tularensis is a tier 1 select agent responsible for tularemia in humans and a wide variety of animal species. Extensive research into understanding the virulence factors of the bacterium has been ongoing to develop an efficacious vaccine. At least two such virulence factors are described as capsules of F. tularensis: the O-antigen capsule and the capsule-like complex (CLC). These two separate entities aid in avoiding host immune defenses but have not been clearly differentiated. These components are distinct and differ in composition and genetic basis. The O-antigen capsule consists of a polysaccharide nearly identical to the lipopolysaccharide (LPS) O antigen, whereas the CLC is a heterogeneous complex of glycoproteins, proteins, and possibly outer membrane vesicles and tubes (OMV/Ts). In this review, the current understanding of these two capsules is summarized, and the historical references to “capsules” of F. tularensis are clarified. A significant amount of research has been invested into the composition of each capsule and the genes involved in synthesis of the polysaccharide portion of each capsule. Areas of future research include further exploration into the molecular regulation and pathways responsible for expression of each capsule and further elucidating the role that each capsule plays in virulence.