van der Ende A, Hopman C T, Dankert J
Department of Medical Microbiology and Reference Laboratory for Bacterial Meningitis, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Infect Immun. 1999 Jun;67(6):2928-34. doi: 10.1128/IAI.67.6.2928-2934.1999.
PorA is an important component in a vaccine against infection with Neisseria meningitidis. However, porA-negative meningococci were isolated from patients, thereby potentially limiting the role of PorA-mediated immunity. To analyze the mechanism by which the porA deletion occurred, the regions upstream and downstream of porA from three meningococcal strains (H44/76, H355, and 860183) were sequenced. The porA upstream region in strain 860183 contains a cluster of 22 repetitive palindromic RS3 core sequences (ATTCCC-N8-GGGAAT) and 10 RS3 core sequences (ATTCCC) in direct orientation. The cluster is flanked by neisserial repeats, so-called Correia elements, and can be subdivided into three repeats of 518 bp followed by a truncated repeat. The porA upstream region of the other two strains showed deletions, probably caused by a recombination between RS3 core sequences. The porA downstream region of H44/76 and H355 contains the IS1106 element followed by a cluster of 10 palindromic RS3 core sequences, 4 RS3 core sequences, and 1 other RS3 core sequence (GGGAAT) and is followed by a Correia element. This cluster can be subdivided into four direct repeats of 370 bp. Strain 860183 had two such repeats instead of four. Sequence analysis of the porA-negative variants indicated that the deletion of porA occurred via a recombination between two copies of the 116-bp region, containing two palindromic RS3 core sequences and a single RS3 core sequence. This region is homologous in the upstream and downstream clusters.
PorA是抗脑膜炎奈瑟菌感染疫苗中的一个重要成分。然而,从患者体内分离出了porA阴性的脑膜炎球菌,从而可能限制了PorA介导的免疫作用。为了分析porA缺失发生的机制,对三株脑膜炎球菌菌株(H44/76、H355和860183)的porA上下游区域进行了测序。860183菌株的porA上游区域包含一组22个重复的回文RS3核心序列(ATTCCC-N8-GGGAAT)和10个同向排列的RS3核心序列(ATTCCC)。该簇两侧是奈瑟菌重复序列,即所谓的科雷亚元件,可细分为三个518 bp的重复序列,后面跟着一个截短的重复序列。其他两株菌株的porA上游区域显示有缺失,可能是由RS3核心序列之间的重组引起的。H44/76和H355的porA下游区域包含IS1106元件,后面跟着一组10个回文RS3核心序列、4个RS3核心序列和1个其他RS3核心序列(GGGAAT),接着是一个科雷亚元件。该簇可细分为四个370 bp的直接重复序列。860183菌株有两个这样的重复序列,而不是四个。对porA阴性变体的序列分析表明,porA的缺失是通过116 bp区域的两个拷贝之间的重组发生的,该区域包含两个回文RS3核心序列和一个单一的RS3核心序列。该区域在上游和下游簇中是同源的。