Surface diversity in Mycoplasma agalactiae is driven by site-specific DNA inversions within the vpma multigene locus

Surface diversity in Mycoplasma agalactiae is driven by site-specific DNA inversions within the vpma multigene locus
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DOI:
10.1128/jb.184.21.5987-5998.2002
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发表时间:
2002-11-01
影响因子:
3.2
通讯作者:
Citti, C
Citti, C
中科院分区:
生物学3区
文献类型:
--
作者:
Glew, MD;Marenda, M;Citti, C

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反刍动物病原体无乳支原体具有一个被称为Vpmas的丰富表达的可变表面脂蛋白家族。Vpma成员之间的表型开关先前与Vpma基因位点内的DNA重排相关,并被认为在疾病发病机制中发挥重要作用。本研究在无乳杆菌型菌株PG2中鉴定了6个vpma基因。所有vpma基因聚集在一个8kb的区域内,共享高度保守的5'非翻译区、脂蛋白信号序列和短n端序列。对连续克隆分离的vpma基因座的分析表明,vpma DNA重排具有位点特异性,并且在所有vpma基因的5'非翻译区中,切割和链交换发生在最小21 bp的区域内。该过程通过有效地将沉默基因的开放阅读框(ORF)连接到基因座内独特的活性启动子序列来控制vpma基因的表达。紧邻vpma位点一端的ORF (xer1)没有发生重排,并且与属于位点特异性xer重组酶的lambda整合酶家族的一个独特的基因子集具有显著的同源性。有人提出,xer1编码一个位点特异性重组酶,该重组酶不参与染色体二聚体的分解,而是负责在无乳杆菌中观察到的vpma特异性重组。
The ruminant pathogen Mycoplasma agalactiae possesses a family of abundantly expressed variable surface lipoproteins called Vpmas. Phenotypic switches between Vpma members have previously been correlated with DNA rearrangements within a locus of vpma genes and are proposed to play an important role in disease pathogenesis. In this study, six vpma genes were characterized in the M. agalactiae type strain PG2. All vpma genes clustered within an 8-kb region and shared highly conserved 5' untranslated regions, lipoprotein signal sequences, and short N-terminal sequences. Analyses of the vpma loci from consecutive clonal isolates showed that vpma DNA rearrangements were site specific and that cleavage and strand exchange occurred within a minimal region of 21 bp located within the 5' untranslated region of all vpma genes. This process controlled expression of vpma genes by effectively linking the open reading frame (ORF) of a silent gene to a unique active promoter sequence within the locus. An ORF (xer1) immediately adjacent to one end of the vpma locus did not undergo rearrangement and had significant homology to a distinct subset of genes belonging to the lambda integrase family of site-specific xer recombinases. It is proposed that xer1 codes for a site-specific recombinase that is not involved in chromosome dimer resolution but rather is responsible for the observed vpma-specific recombination in M. agalactiae.