Phagocytic superoxide specifically damages an extracytoplasmic target to inhibit or kill Salmonella.
Phagocytic superoxide specifically damages an extracytoplasmic target to inhibit or kill Salmonella.
复制标题
吞噬超氧化物特异性损害外质靶标可抑制或杀死沙门氏菌。
DOI：
10.1371/journal.pone.0004975
复制
发表时间：
2009
期刊：
影响因子：
3.7
通讯作者：
Slauch JM
中科院分区：
文献类型：
--
作者：
Craig M;Slauch JM
吞噬细胞氧化爆发是先天免疫的主要效应器，可防止细菌感染。然而，活性氧（ROS）杀死或抑制细菌的机制尚不清楚。人们通常认为 DNA 是氧化损伤的主要目标，这与细菌细胞质中内源产生的 ROS 的已知影响一致。但大多数研究未能区分宿主衍生的 ROS 的影响与内源性细菌来源造成的损害。我们利用肠沙门氏菌鼠伤寒血清型在巨噬细胞中存活的能力和系统的遗传易处理性来检验吞噬超氧化物会损害包括 DNA 在内的细胞质靶标的假设。 SodCI 是一种周质铜锌超氧化物歧化酶 (SOD)，有助于鼠伤寒沙门氏菌在巨噬细胞中的存活。通过竞争性毒力测定，我们询问 sodCI 是否与各种细胞质系统存在遗传相互作用。我们发现 SodCI 的作用独立于细胞质 SOD、SodA 和 SodB。此外，SodCI 独立于碱基切除修复系统和 RuvAB 发挥作用，参与 DNA 修复。尽管 sodCI 确实显示出与 recA 的遗传相互作用，但这显然与重组无关，并且可能是由于 recA 突变的多效性效应。综上所述，这些结果表明吞噬超氧化物对细菌的抑制主要是胞质外靶标受损的结果。
The phagocytic oxidative burst is a primary effector of innate immunity that protects against bacterial infection. However, the mechanism by which reactive oxygen species (ROS) kill or inhibit bacteria is not known. It is often assumed that DNA is a primary target of oxidative damage, consistent with known effects of endogenously produced ROS in the bacterial cytoplasm. But most studies fail to distinguish between effects of host derived ROS versus damage caused by endogenous bacterial sources. We took advantage of both the ability of Salmonella enterica serovar Typhimurium to survive in macrophages and the genetic tractability of the system to test the hypothesis that phagocytic superoxide damages cytoplasmic targets including DNA. SodCI is a periplasmic Cu-Zn superoxide dismutase (SOD) that contributes to the survival of Salmonella Typhimurium in macrophages. Through competitive virulence assays, we asked if sodCI has a genetic interaction with various cytoplasmic systems. We found that SodCI acts independently of cytoplasmic SODs, SodA and SodB. In addition, SodCI acts independently of the base excision repair system and RuvAB, involved in DNA repair. Although sodCI did show genetic interaction with recA, this was apparently independent of recombination and is presumably due to the pleiotropic effects of a recA mutation. Taken together, these results suggest that bacterial inhibition by phagocytic superoxide is primarily the result of damage to an extracytoplasmic target.
登录
查看更多内容
影响因子：
3.5
作者：
CHEREPANOV, PP;WACKERNAGEL, W
通讯作者：
WACKERNAGEL, W
影响因子：
15.9
作者：
BUCHMEIER, NA;LIBBY, SJ;FANG, FC
通讯作者：
FANG, FC
影响因子：
3.6
作者：
BUCHMEIER, NA;LIPPS, CJ;HEFFRON, F
通讯作者：
HEFFRON, F
影响因子：
3.2
作者：
Cano, DA;Pucciarelli, MG;Casadesús, J
通讯作者：
Casadesús, J
影响因子：
3.5
作者：
Ellermeier, CD;Janakiraman, A;Slauch, JM
通讯作者：
Slauch, JM