Sisti Federico, Fernández Julieta, Cordero Andrés, Casabuono Adriana, Couto Alicia, Hozbor Daniela
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.
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.
Bioorg Med Chem Lett. 2017 Feb 1;27(3):432-436. doi: 10.1016/j.bmcl.2016.12.049. Epub 2016 Dec 21.
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.
支气管败血波氏杆菌主要在包括人类在内的哺乳动物中引发呼吸道疾病。尽管已经针对脂多糖（LPS）在感染过程中的作用以及刺激先天性和适应性免疫反应开展了大量研究，但LPS合成所涉及的机制仍然未知。在此背景下，我们在支气管败血波氏杆菌基因组中搜索假定的糖基转移酶。我们发现了可能编码参与LPS结构糖基取代的酶的基因。我们决定分析与百日咳博德特氏菌中先前描述的LPS生物合成位点相邻的BB3394至BB3400基因。特别是，BB3394在已测序的支气管败血波氏杆菌基因组中的保守性表明该基因对细菌正常生理功能的重要性。如其他LPS突变体一样，BB3394的缺失消除了对天然血清的抗性。当分析纯化的LPS时，发现了LPS核心结构的差异。特别是，从BB3394缺失突变体获得的LPS中，核心中不存在GalNA分支糖取代。核心LPS中GalNA的缺失改变了体内免疫反应，但能够诱导针对支气管败血波氏杆菌感染的保护性反应。
