Hammerschmidt S, Müller A, Sillmann H, Mühlenhoff M, Borrow R, Fox A, van Putten J, Zollinger W D, Gerardy-Schahn R, Frosch M
Institut für Medizinische Mikrobiologie, Medizinische Hochschule Hannover, Germany.
Mol Microbiol. 1996 Jun;20(6):1211-20. doi: 10.1111/j.1365-2958.1996.tb02641.x.
A mechanism of capsular polysaccharide phase variation in Neisseria meningitidis is described. Meningococcal cells of an encapsulated serogroup B strain were used in invasion assays. Only unencapsulated variants were found to enter epithelial cells. Analysis of one group of capsule-deficient variants indicated that the capsular polysaccharide was re-expressed at a frequency of 10(-3). Measurement of enzymatic activities involved in the biosynthesis of the alpha-2,8 polysialic acid capsule showed that polysialyltransferase (PST) activity was absent in these capsule-negative variants. Nucleotide sequence analysis of siaD revealed an insertion or a deletion of one cytidine residue within a run of (dC)7 residues at position 89, resulting in a frameshift and premature termination of translation. We analysed unencapsulated isolates from carriers and encapsulated case isolates collected during an outbreak of meningococcal disease. Further paired blood-culture isolates and unencapsulated nasopharyngeal isolates from patients with meningococcal meningitis were examined. In all unencapsulated strains analysed we found an insertion or deletion within the oligo-(dC) stretch within siaD, resulting in a frameshift and loss of capsule formation. All encapsulated isolates, however, had seven dC residues at this position, indicating a correlation between capsule phase variation and bacterial invasion and the outbreak of meningococcal disease.
本文描述了脑膜炎奈瑟菌中荚膜多糖相变的机制。在侵袭试验中使用了一株B群荚膜血清型菌株的脑膜炎球菌细胞。结果发现只有无荚膜变体能够进入上皮细胞。对一组荚膜缺陷变体的分析表明，荚膜多糖的重新表达频率为10^(-3)。对参与α-2,8多聚唾液酸荚膜生物合成的酶活性进行测定，结果显示这些无荚膜变体中不存在多聚唾液酸转移酶（PST）活性。对siaD的核苷酸序列分析显示，在第89位的(dC)7残基序列中插入或缺失了一个胞嘧啶残基，导致移码并提前终止翻译。我们分析了在脑膜炎球菌病暴发期间从携带者中分离出的无荚膜菌株以及从病例中分离出的有荚膜菌株。进一步检查了来自脑膜炎球菌性脑膜炎患者的配对血培养分离株和无荚膜鼻咽分离株。在所有分析的无荚膜菌株中，我们发现在siaD基因内的寡聚(dC)序列中有插入或缺失，导致移码并丧失荚膜形成能力。然而，所有有荚膜的分离株在该位置都有七个dC残基，表明荚膜相变与细菌侵袭以及脑膜炎球菌病暴发之间存在相关性。
