Regué Miguel, Izquierdo Luis, Fresno Sandra, Piqué Núria, Corsaro Maria Michela, Naldi Teresa, De Castro Cristina, Waidelich Dietmar, Merino Susana, Tomás Juan M
Departamento de Microbiología i Parasitología Sanitarias, Facultad de Farmacia, Universidad de Barcelona, Spain.
J Bacteriol. 2005 Jun;187(12):4198-206. doi: 10.1128/JB.187.12.4198-4206.2005.
Up to now only one major type of core oligosaccharide has been found in the lipopolysaccharide of all Klebsiella pneumoniae strains analyzed. Applying a different screening approach, we identified a novel Klebsiella pneumoniae core (type 2). Both Klebsiella core types share the same inner core and the outer-core-proximal disaccharide, GlcN-(1,4)-GalA, but they differ in the GlcN substituents. In core type 2, the GlcpN residue is substituted at the O-4 position by the disaccharide beta-Glcp(1-6)-alpha-Glcp(1, while in core type 1 the GlcpN residue is substituted at the O-6 position by either the disaccharide alpha-Hep(1-4)-alpha-Kdo(2 or a Kdo residue (Kdo is 3-deoxy-D-manno-octulosonic acid). This difference correlates with the presence of a three-gene region in the corresponding core biosynthetic clusters. Engineering of both core types by interchanging this specific region allowed studying the effect on virulence. The replacement of Klebsiella core type 1 in a highly type 2 virulent strain (52145) induces lower virulence than core type 2 in a murine infection model.
到目前为止,在所有已分析的肺炎克雷伯菌菌株的脂多糖中,仅发现了一种主要类型的核心寡糖。通过应用不同的筛选方法,我们鉴定出了一种新型的肺炎克雷伯菌核心(2型)。两种肺炎克雷伯菌核心类型共享相同的内核和靠近外核的二糖GlcN-(1,4)-GalA,但它们在GlcN取代基上有所不同。在2型核心中,GlcpN残基在O-4位被二糖β-Glcp(1-6)-α-Glcp(1取代,而在1型核心中,GlcpN残基在O-6位被二糖α-Hep(1-4)-α-Kdo(2或一个Kdo残基(Kdo是3-脱氧-D-甘露糖辛酸)取代。这种差异与相应核心生物合成簇中一个三基因区域的存在相关。通过交换这个特定区域对两种核心类型进行工程改造,从而能够研究其对毒力的影响。在小鼠感染模型中,将高毒力的2型菌株(52145)中的1型肺炎克雷伯菌核心替换为2型核心,所诱导的毒力低于2型核心。