Either periplasmic tethering or protease resistance is sufficient to allow a SodC to protect Salmonella enterica serovar Typhimurium from phagocytic superoxide.
Either periplasmic tethering or protease resistance is sufficient to allow a SodC to protect Salmonella enterica serovar Typhimurium from phagocytic superoxide.
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DOI：
10.1111/j.1365-2958.2011.07884.x
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发表时间：
2011-11
影响因子：
3.6
通讯作者：
Slauch JM
中科院分区：
文献类型：
--
作者：
Rushing MD;Slauch JM
鼠伤寒沙门氏菌通过产生周质超氧化物歧化酶SodCI来对抗吞噬细胞的超氧化物歧化酶。同源蛋白SodCII也在感染过程中产生，但对毒力没有贡献。这两种蛋白质在物理上的不同之处在于，SodCI是二聚体的，对蛋白酶有抵抗力，并且非共价连接在周质中。相反，SodCII是一种蛋白酶敏感的单体，通常通过渗透休克从周质中释放出来。为了确定哪些特性与毒力相关，我们构建了20多个具有酶功能的杂交SODC蛋白，并检测了它们的蛋白酶敏感性、渗透休克释放、多聚化和对金属辅因子的亲和力。蛋白酶易感性定位于SodCII的C末端，而SodCI残基120-131是拴系所必需的。抗蛋白酶的SodCII杂交种能够在侵染过程中替代SodCI。有趣的是，一种被拴住但对蛋白酶敏感的SodCII杂交种也能够提供保护。因此，系留或蛋白酶抗性足以使SODC在感染期间发挥作用。这些结果支持我们的模型，即在巨噬细胞中，沙门氏菌的外膜部分被抗菌肽破坏。包括SodCII在内的周质蛋白被释放，和/或吞噬细胞蛋白酶获得进入。SodCI既被束缚在周质内，又具有抗蛋白酶活性，因此能够存活下来，为超氧化物解毒。
Salmonella Typhimurium combats phagocytic superoxide by producing the periplasmic superoxide dismutase, SodCI. The homologous protein, SodCII, is also produced during infection, but does not contribute to virulence. The proteins physically differ in that SodCI is dimeric, protease resistant, and non-covalently tethered within the periplasm. Conversely, SodCII is a protease sensitive monomer that is released normally from the periplasm by osmotic shock. To identify which properties correlate with virulence, we constructed over 20 enzymatically functional hybrid SodC proteins and assayed them for protease susceptibility, release by osmotic shock, multimerization, and affinity for metal cofactors. Protease susceptibility maps to the C-terminus of SodCII, while SodCI residues 120–131 are required for tethering. A protease resistant SodCII hybrid was able to substitute for SodCI during infection. Interestingly, a tethered but protease sensitive SodCII hybrid was also able to confer protection. Thus, either tethering or protease resistance is sufficient for a SodC to function during infection. These results support our model that in the macrophage, the outer membrane of Salmonella is partially disrupted by antimicrobial peptides. Periplasmic proteins, including SodCII, are released and/or phagocytic proteases gain access. SodCI is both tethered within the periplasm and protease resistant, thereby surviving to detoxify superoxide.
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影响因子：
15.3
作者：
Mastroeni, P;Vazquez-Torres, A;Fang, F C;Xu, Y;Khan, S;Hormaeche, C E;Dougan, G
通讯作者：
Dougan, G
影响因子：
3.2
作者：
Krishnakumar, R;Craig, M;Slauch, JM
通讯作者：
Slauch, JM
影响因子：
3.5
作者：
Ellermeier, CD;Janakiraman, A;Slauch, JM
通讯作者：
Slauch, JM
影响因子：
4.8
作者：
Ammendola, Serena;Pasquali, Paolo;Battistoni, Andrea
通讯作者：
Battistoni, Andrea
影响因子：
3.2
作者：
Golubeva, Yekaterina A.;Slauch, James M.
通讯作者：
Slauch, James M.