Gaasbeek Esther J, van der Wal Fimme J, van Putten Jos P M, de Boer Paulo, van der Graaf-van Bloois Linda, de Boer Albert G, Vermaning Bart J, Wagenaar Jaap A
Department of Bacteriology and TSEs, Central Veterinary Institute of Wageningen UR, 8219 PH Lelystad, The Netherlands.
J Bacteriol. 2009 Jun;191(12):3785-93. doi: 10.1128/JB.01817-08. Epub 2009 Apr 17.
The presence and functionality of DNA repair mechanisms in Campylobacter jejuni are largely unknown. In silico analysis of the complete translated genome of C. jejuni NCTC 11168 suggests the presence of genes involved in methyl-directed mismatch repair (MMR), nucleotide excision repair, base excision repair (BER), and recombinational repair. To assess the functionality of these putative repair mechanisms in C. jejuni, mutS, uvrB, ung, and recA knockout mutants were constructed and analyzed for their ability to repair spontaneous point mutations, UV irradiation-induced DNA damage, and nicked DNA. Inactivation of the different putative DNA repair genes did not alter the spontaneous mutation frequency. Disruption of the UvrB and RecA orthologues, but not the putative MutS or Ung proteins, resulted in a significant reduction in viability after exposure to UV irradiation. Assays performed with uracil-containing plasmid DNA showed that the putative uracil-DNA glycosylase (Ung) protein, important for initiation of the BER pathway, is also functional in C. jejuni. Inactivation of recA also resulted in a loss of natural transformation. Overall, the data indicate that C. jejuni has multiple functional DNA repair systems that may protect against DNA damage and limit the generation of genetic diversity. On the other hand, the apparent absence of a functional MMR pathway may enhance the frequency of on-and-off switching of phase variable genes typical for C. jejuni and may contribute to the genetic heterogeneity of the C. jejuni population.
空肠弯曲菌中DNA修复机制的存在及其功能在很大程度上尚不清楚。对空肠弯曲菌NCTC 11168完整翻译基因组的计算机分析表明,存在参与甲基定向错配修复(MMR)、核苷酸切除修复、碱基切除修复(BER)和重组修复的基因。为了评估这些假定的修复机制在空肠弯曲菌中的功能,构建了mutS、uvrB、ung和recA基因敲除突变体,并分析它们修复自发点突变、紫外线照射诱导的DNA损伤和切口DNA的能力。不同假定DNA修复基因的失活并未改变自发突变频率。UvrB和RecA直系同源物的破坏,而非假定的MutS或Ung蛋白,导致紫外线照射后活力显著降低。用含尿嘧啶的质粒DNA进行的试验表明,对BER途径起始重要的假定尿嘧啶-DNA糖基化酶(Ung)蛋白在空肠弯曲菌中也具有功能。recA的失活也导致自然转化丧失。总体而言,数据表明空肠弯曲菌具有多种功能性DNA修复系统,这些系统可能防止DNA损伤并限制遗传多样性的产生。另一方面,功能性MMR途径的明显缺失可能会增加空肠弯曲菌典型的相位可变基因的开-关切换频率,并可能导致空肠弯曲菌群体的遗传异质性。