Loss of both Holliday junction processing pathways is synthetically lethal in the presence of gonococcal pilin antigenic variation
Loss of both Holliday junction processing pathways is synthetically lethal in the presence of gonococcal pilin antigenic variation
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DOI：
10.1111/j.1365-2958.2006.05213.x
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发表时间：
2006-07-01
影响因子：
3.6
通讯作者：
Seifert, H. Steven
中科院分区：
文献类型：
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作者：
Sechman, Eric V.;Kline, Kimberly A.;Seifert, H. Steven
淋球菌（Neisseria gonorrhoeae，Gc）是一种通过抗原变异（antigenic variation，Av）实现免疫逃避的致病菌。我们表明，RuvABC和RecG霍利迪连接（HJ）加工途径都需要重组修复，每个可以在遗传转移过程中发挥作用，都需要菌毛蛋白AV。双突变体的分析表明，RecG或RuvAB HJ加工途径必须是功能性的正常生长的Gc时，RecA的表达。RecA表达的HJ加工缺陷幸存者富集携带pilE基因大缺失的非纤毛细菌。防止菌毛蛋白变异的突变，如recO、recQ和顺式作用pilE转座子插入，都拯救了HJ加工缺陷菌株的RecA依赖性生长抑制。这些结果表明，菌毛蛋白Av产生重组中间体，其必须通过任一种HJ途径加工以保持活力，但需要两种HJ加工途径以产生菌毛蛋白变体。通过频繁的重组反应产生多样性的需要创造了一种情况，其中HJ加工机制对于生长是必不可少的，并为抗淋病的新型抗菌剂提供了可能的靶点。
The obligate human pathogen Neisseria gonorrhoeae (Gc) has co-opted conserved recombination pathways to achieve immune evasion by way of antigenic variation (Av). We show that both the RuvABC and RecG Holliday junction (HJ) processing pathways are required for recombinational repair, each can act during genetic transfer, and both are required for pilin Av. Analysis of double mutants shows that either the RecG or RuvAB HJ processing pathway must be functional for normal growth of Gc when RecA is expressed. HJ processing-deficient survivors of RecA expression are enriched for non-piliated bacteria that carry large deletions of the pilE gene. Mutations that prevent pilin variation such as recO, recQ, and a cis-acting pilE transposon insertion all rescue the RecA-dependent growth inhibition of a HJ processing-deficient strain. These results show that pilin Av produces a recombination intermediate that must be processed by either one of the HJ pathways to retain viability, but requires both HJ processing pathways to yield pilin variants. The need for diversity generation through frequent recombination reactions creates a situation where the HJ processing machinery is essential for growth and presents a possible target for novel antimicrobials against gonorrhoea.