Claus Heike, Borrow Ray, Achtman Mark, Morelli Giovanna, Kantelberg Carmen, Longworth Emma, Frosch Matthias, Vogel Ulrich
Institut für Hygiene und Mikrobiologie, Universität Würzburg, Josef-Schneider-Str. 2, 97080 Würzburg, Germany.
Mol Microbiol. 2004 Jan;51(1):227-39. doi: 10.1046/j.1365-2958.2003.03819.x.
Capsular polysaccharides of serogroup C, W-135 and Y meningococci were previously reported to be O-acetylated at the sialic acid residues. There is evidence that O-acetylation affects the immunogenicity of polysaccharide vaccines. We identified genes indispensable for O-acetylation of serogroup C, W-135 and Y meningococci downstream of the capsule synthesis genes siaA-D. The genes were co-transcribed with the sia operon as shown by reverse transcription polymerase chain reaction analysis. The putative capsular polysaccharide O-acetyltransferases were designated OatC and OatWY. The protein OatWY of serogroups W-135 and Y showed sequence homologies to members of the NodL-LacA-CysE family of bacterial acetyltransferases, whereas no sequence homology with any known protein in the different databases was found for the serogroup C protein OatC. In serogroup W-135 and Y meningococci, several clonal lineages either lacked OatWY or OatWY was inactivated by insertion of IS1301. For serogroup C meningococci, we observed in vitro phase variation of O-acetylation, which resulted from slipped-strand mispairing in homopolymeric tracts. This finding explains the observation of naturally occurring de-O-acetylated serogroup C meningococci. Our report is the first description of sequences of sialic acid O-acetyltransferase genes that have not been cloned from either other bacterial or mammalian organisms.
以前有报道称,C群、W-135群和Y群脑膜炎球菌的荚膜多糖在唾液酸残基处发生了O-乙酰化。有证据表明,O-乙酰化会影响多糖疫苗的免疫原性。我们在荚膜合成基因siaA-D下游鉴定出了C群、W-135群和Y群脑膜炎球菌O-乙酰化所必需的基因。逆转录聚合酶链反应分析表明,这些基因与sia操纵子共同转录。假定的荚膜多糖O-乙酰转移酶被命名为OatC和OatWY。W-135群和Y群的蛋白OatWY与细菌乙酰转移酶的NodL-LacA-CysE家族成员具有序列同源性,而C群蛋白OatC在不同数据库中未发现与任何已知蛋白的序列同源性。在W-135群和Y群脑膜炎球菌中,几个克隆谱系要么缺乏OatWY,要么OatWY因IS1301的插入而失活。对于C群脑膜炎球菌,我们观察到了O-乙酰化的体外相变,这是由同聚物区段中的滑链错配引起的。这一发现解释了天然存在的去O-乙酰化C群脑膜炎球菌的现象。我们的报告首次描述了尚未从其他细菌或哺乳动物生物体中克隆的唾液酸O-乙酰转移酶基因的序列。