Regué Miguel, Izquierdo Luis, Fresno Sandra, Jimenez Natalia, Piqué Nuria, Corsaro M Michela, Parrilli Michelangelo, Naldi Teresa, Merino Susana, Tomás Juan M
Departamento de Microbiología y Parasitología Sanitarias, Facultad de Farmacia, Universidad de Barcelona, Av. Joan XXIII s/n, 08028 Barcelona, Spain.
J Biol Chem. 2005 Nov 4;280(44):36648-56. doi: 10.1074/jbc.M506278200. Epub 2005 Aug 30.
The core lipopolysaccharide (LPS) of Klebsiella pneumoniae is characterized by the presence of disaccharide alphaGlcN-(1,4)-alphaGalA attached by an alpha1,3 linkage to l-glycero-d-manno-heptopyranose II (ld-HeppII). Previously it has been shown that the WabH enzyme catalyzes the incorporation of GlcNAc from UDP-GlcNAc to outer core LPS. The presence of GlcNAc instead of GlcN and the lack of UDP-GlcN in bacteria indicate that an additional enzymatic step is required. In this work we identified a new gene (wabN) in the K. pneumoniae core LPS biosynthetic cluster. Chemical and structural analysis of K. pneumoniae non-polar wabN mutants showed truncated core LPS with GlcNAc instead of GlcN. In vitro assays using LPS truncated at the level of d-galacturonic acid (GalA) and cell-free extract containing WabH and WabN together led to the incorporation of GlcN, whereas none of them alone were able to do it. This result suggests that the later enzyme (WabN) catalyzes the deacetylation of the core LPS containing the GlcNAc residue. Thus, the incorporation of the GlcN residue to core LPS in K. pneumoniae requires two distinct enzymatic steps. WabN homologues are found in Serratia marcescens and some Proteus strains that show the same disaccharide alphaGlcN-(1,4)-alphaGalA attached by an alpha1,3 linkage to ld-HeppII.
肺炎克雷伯菌的核心脂多糖(LPS)的特征是存在通过α1,3键连接到l-甘油-d-甘露庚糖II(ld-HeppII)上的二糖αGlcN-(1,4)-αGalA。此前已表明,WabH酶催化UDP-GlcNAc中的GlcNAc掺入外核心LPS。细菌中存在GlcNAc而非GlcN且缺乏UDP-GlcN,这表明还需要一个额外的酶促步骤。在这项研究中,我们在肺炎克雷伯菌核心LPS生物合成簇中鉴定出一个新基因(wabN)。对肺炎克雷伯菌非极性wabN突变体的化学和结构分析显示,核心LPS被截断,其中的GlcN被GlcNAc取代。使用在d-半乳糖醛酸(GalA)水平截断的LPS以及同时含有WabH和WabN的无细胞提取物进行的体外试验导致了GlcN的掺入,而单独使用它们中的任何一种都无法做到这一点。这一结果表明,后一种酶(WabN)催化含有GlcNAc残基的核心LPS的脱乙酰化。因此,肺炎克雷伯菌中GlcN残基掺入核心LPS需要两个不同的酶促步骤。在粘质沙雷氏菌和一些变形杆菌菌株中发现了WabN同源物,它们也显示出通过α1,3键连接到ld-HeppII上的相同二糖αGlcN-(1,4)-αGalA。