Regulatory and structural differences in the Cu, Zn-superoxide dismutases of Salmonella enterica and their significance for virulence
Regulatory and structural differences in the Cu, Zn-superoxide dismutases of Salmonella enterica and their significance for virulence
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DOI：
10.1074/jbc.m710499200
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发表时间：
2008-05-16
影响因子：
4.8
通讯作者：
Battistoni, Andrea
中科院分区：
文献类型：
--
作者：
Ammendola, Serena;Pasquali, Paolo;Battistoni, Andrea
许多最毒力的沙门氏菌菌株产生两种不同的Cu，Zn-超氧化物歧化酶（SodCI和SodCII）。噬菌体编码的SodCI酶对沙门氏菌的毒力有更大的贡献。我们已经进行了详细的比较沙门氏菌SodC酶的功能，结构和监管特性。在这里，我们证明了SodCI和SodCII在比活性、蛋白酶抗性、金属亲和力和过氧化活性方面不同，二聚体SodCI表现出上级稳定性和活性。特别地，单体SodCII在不存在锌的情况下不能保留其催化铜离子。我们还发现，SodCI和SodCII的差异受氧，锌的可用性，和转录调节FNR。SodCII在厌氧条件下强烈下调，并依赖于高亲和力ZnuABC锌转运系统，而SodCI在体外和巨噬细胞内的积累是FNR依赖性的。我们已经证实了早期的研究结果，即SodCII在细胞内沙门氏菌中的积累是可以忽略不计的，而SodCI在巨噬细胞中强烈上调。我们的观察结果表明，表达，活性和稳定性的差异有助于解释噬菌体编码的SodCI酶对沙门氏菌毒力的独特贡献。
Many of the most virulent strains of Salmonella enterica produce two distinct Cu, Zn-superoxide dismutases (SodCI and SodCII). The bacteriophage-encoded SodCI enzyme makes the greater contribution to Salmonella virulence. We have performed a detailed comparison of the functional, structural, and regulatory properties of the Salmonella SodC enzymes. Here we demonstrate that SodCI and SodCII differ with regard to specific activity, protease resistance, metal affinity, and peroxidative activity, with dimeric SodCI exhibiting superior stability and activity. In particular, monomeric SodCII is unable to retain its catalytic copper ion in the absence of zinc. We have also found that SodCI and SodCII are differentially affected by oxygen, zinc availability, and the transcriptional regulator FNR. SodCII is strongly down-regulated under anaerobic conditions and dependent on the high affinity ZnuABC zinc transport system, whereas SodCI accumulation in vitro and within macrophages is FNR-dependent. We have confirmed earlier findings that SodCII accumulation in intracellular Salmonella is negligible, whereas SodCI is strongly up-regulated in macrophages. Our observations demonstrate that differences in expression, activity, and stability help to account for the unique contribution of the bacteriophage-encoded SodCI enzyme to Salmonella virulence.