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Modifications of Bordetella bronchiseptica core lipopolysaccharide influence immune response without affecting protective activity
Authors:Federico Sisti  Julieta Fernández  Andrés Cordero  Adriana Casabuono  Alicia Couto  Daniela Hozbor
Affiliation:1. Instituto de Biotecnología y Biología Molecular, CCT La Plata CONICET, Departamento de Ciencias Biológicas, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Calles 47 y 115, 1900 La Plata, Argentina;2. CIHIDECAR, Departamento de Química Orgánica, Facultad de Cs Exactas y Naturales, Universidad de Buenos Aires, 1428 Bs. As., Argentina
Abstract:Bordetella bronchiseptica produces respiratory disease primarily in mammals including humans. Although a considerably amount of research has been generated regarding lipopolysaccharide (LPS) role during infection and stimulating innate and adaptive immune response, mechanisms involved in LPS synthesis are still unknown. In this context we searched in B. bronchiseptica genome for putative glycosyltransferases. We found possible genes codifying for enzymes involved in sugar substitution of the LPS structure. We decided to analyse BB3394 to BB3400 genes, closed to a previously described LPS biosynthetic locus in B. pertussis. Particularly, conservation of BB3394 in sequenced B. bronchiseptica genomes suggests the importance of this gene for bacteria normal physiology. Deletion of BB3394 abolished resistance to naive serum as described for other LPS mutants. When purified LPS was analyzed, differences in the LPS core structure were found. Particularly, a GalNA branched sugar substitution in the core was absent in the LPS obtained from BB3394 deletion mutant. Absence of GalNA in core LPS alters immune response in vivo but is able to induce protective response against B. bronchiseptica infection.
Keywords:Lipopolysaccharide  Bordetella  Glycosyltransferase  Kdo  Hep, Heptose  GlcA  glucuronic acid  GlcN  glucosamine  GlcNAc  N-acetylglucosamine  FucN, Fuc2NAc4N  2-acetamido 4-amino 2,4,6-trideoxy-galactose  Man2,3NAcA  2,3-diacetamido-2,3-dideoxymannuronic acid  GlcNAc  N-acetylglucosamine  Man2,3NAcAN  2,3-diacetamido-2,3-dideoxymannuronamide  GalNAc3NAcA  2,3-diacetamido-2,3-dideoxygalacturonic acid  GlcNAc3NAcAN  2,3-diacetamido-2,3-dideoxy-glucuronamide  Lac type  2-Nacetyl, 3-Nformyl, 4N-(2 metoxypropionyl)-2,3,4-triamino 2,3,4-trideoxy-α-galacturonamide
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