Structural Analysis of Francisella tularensis Cell Surface Carbohydrates using High Resolution and Accuracy Mass Spectrometry

摘要

Francisella tularensis (Ft) is the gram-negative bacterium that causes tularemia, an infectious disease in humans and other mammals such as aquatic rodents and rabbits. Ft is classified as a category A Select Agent by the Centers for Disease Control because of its low infectious dose and high mortality rate. Therefore, development of vaccines and immunotherapeutics against Ft is essential for public health. Lipopolysaccharide (LPS) has been reported to be a protective Ft antigen. The structure of Ft LPS has been studied using NMR and mass spectrometry (1,2). The O-antigen was identified as containing a variable number of the tetrasaccharide repeat, (GalNAcAN)_(2)(QuiNAc)(Qui4NFM) attached to one of two types of core structures: (Hex)_(3)(HexNAc)(Kdo) or (Hex)_(4)(HexNAc)(Kdo). Capsular polysaccharide (CPS), which contaminates LPS preparations, was recently shown to contain the same tetrasaccharide repeat found in Ft O-antigen but no core, and to confer immune protection against Ft LVS challenge in mice (3).