Functional analysis of Borrelia burgdorferi uvrA in DNA damage protection
Functional analysis of Borrelia burgdorferi uvrA in DNA damage protection
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DOI：
10.1111/j.1574-6968.2011.02226.x
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发表时间：
2011-04-01
影响因子：
2.1
通讯作者：
Cabello, Felipe C.
中科院分区：
文献类型：
--
作者：
Sambir, Mariya;Ivanova, Larisa B.;Cabello, Felipe C.
细菌病原体面临来自宿主吞噬细胞产生的DNA损伤剂的持续挑战。虽然伯氏疏螺旋体似乎比具有较大基因组的病原体具有少得多的DNA修复酶，但它确实含有uvr A和uvr B的同源物（核酸内切酶ABC的亚基A和B）。作为探索uvrA（Bbu）的生理功能及其在面对DNA损伤剂时在宿主中生存的可能作用的第一步，通过靶向失活分离出部分缺失的uvrA突变体。紫外线照射、丝裂霉素C（MMC）和过氧化氢对野生型B无影响，但对突变株的生长有明显的抑制作用。burgdorferi，其对pH 6.0-6.8和活性氮中间体的响应与野生型亲本菌株相似。紫外线照射，MMC和过氧化物的失活突变体的敏感性是由一个染色体外拷贝的uvrA（Bbu）的补充。我们得出结论，uvrA（Bbu）在B中是功能性的。burgdorferi。
Bacterial pathogens face constant challenges from DNA-damaging agents generated by host phagocytes. Although Borrelia burgdorferi appears to have much fewer DNA repair enzymes than pathogens with larger genomes, it does contain homologues of uvrA and uvrB (subunits A and B of excinuclease ABC). As a first step to exploring the physiologic function of uvrA(Bbu) and its possible role in survival in the host in the face of DNA-damaging agents, a partially deleted uvrA mutant was isolated by targeted inactivation. While growth of this mutant was markedly inhibited by UV irradiation, mitomycin C (MMC) and hydrogen peroxide at doses that lacked effect on wild-type B. burgdorferi, its response to pH 6.0-6.8 and reactive nitrogen intermediates was similar to that of the wild-type parental strain. The sensitivity of the inactivation mutant to UV irradiation, MMC and peroxide was complemented by an extrachromosomal copy of uvrA(Bbu). We conclude that uvrA(Bbu) is functional in B. burgdorferi.