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Taxonomic group: bacteria / Proteobacteria (Phylum: Proteobacteria)
Host organism: Homo sapiens
Associated disease: tularemia [ICD11: 1B94

, ICD11: XN0BX

]; infection due to Francisella tularensis [ICD11: XN0BX

]

NCBI PubMed ID: 24452684
Publication DOI: 10.1128/IAI.01640-13
Journal NLM ID: 0246127
Publisher: American Society for Microbiology
Correspondence: Bradley D. Jones <bradley-jones

uiowa.edu>
Institutions: Department of Microbiology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA, Sciences Division/Microbiology, Pacific Northwest National Laboratory, Richland, Washington, USAd, The Buck Institute for Age Research, Novato, California, USA, The Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, USA, Midwest Regional Center for Excellence in Biodefense and Emerging Infectious Disease Research, Washington University, St. Louis, Missouri, USA

The virulence factors mediating Francisella pathogenesis are being investigated with emphasis on understanding how the organism evades innate immunity mechanisms. F. tularensis produces a lipopolysaccharide (LPS) that is essentially inert and a polysaccharide capsule that helps the organism evade detection by components of innate immunity. We have identified, from a F. tularensis Schu S4 mutant library, strains that are disrupted for capsule and O-antigen production. These serum-sensitive strains lack both capsule production and O-antigen laddering. Analysis of the predicted protein sequences of the disrupted genes (FTT1236 and FTT1238c) revealed similarity to waa (rfa) biosynthetic genes in other bacteria. Mass spectrometry further revealed that these proteins are involved in LPS core sugar biosynthesis and the ligation of O-antigen to the LPS core sugars. The LD50 values of these strains are increased 100- to 1000-fold for mice. Histopathology revealed that the immune response to the F. tularensis mutant strains was significantly different than that observed with wild type infected mice. The lung tissue from mutant infected mice had widespread necrotic debris but the spleens lacked necrosis and displayed neutrophilia. In contrast, the lungs of wild type infected mice had nominal necrosis but the spleens had widespread necrosis. These data indicate that murine death caused by the wild type strains occurs by a mechanism different from that by which the mutant strains killed mice. Mice immunized with these mutant strains displayed greater than ten-fold protective effects against virulent type A F. tularensis challenge.

Lipopolysaccharide, O-antigen, Francisella tularensis, virulence factor

Structure type: oligomer
Location inside paper: p.1529, fig.3, E
Aglycon: lipid A
Compound class: LOS
Contained glycoepitopes: IEDB_130648,IEDB_130650,IEDB_130658,IEDB_130659,IEDB_130701,IEDB_137473,IEDB_137485,IEDB_1391961,IEDB_141584,IEDB_142488,IEDB_144983,IEDB_144998,IEDB_146664,IEDB_152206,IEDB_153219,IEDB_244149,IEDB_885822,IEDB_983930,IEDB_983931,SB_192,SB_44,SB_67,SB_72

Methods: GC-MS, de-O-acylation, ELISA, MALDI-MS, MS/MS, biological assays, composition analysis, genetic methods, immunoblotting, PAGE
Biosynthesis and genetic data: genetic data
Comments, role: Francisella tularensis LVS 00706::TrgTn mutant strain.

Related record ID(s): 30122
NCBI Taxonomy refs (TaxIDs): 263
Reference(s) to other database(s): GTC:G42181OV
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There are 10 chemically distinct structures. Please, select:

CC(=O)N[C@H]1[C@@H](O[C@@H]2[C@H](O[C@H]3[C@H](O)[C@H](O[C@@H]4O[C@H](CO)[C@@H](O)[C@H](O)[C@H]4O)[C@@H](O[C@H]4[C@@H]([C@H](O)CO)O[C@@](O)(C(=O)OC5(C(=O)O)C[C@@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O5)C[C@H]4O)O[C@@H]3CO)O[C@H](CO)[C@@H](O)[C@@H]2O[C@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)O[C@H](CO)[C@H](O)[C@@H]1O

SVG MW SMILES 3D mol Ionize