DNA-REPAIR IS MORE IMPORTANT THAN CATALASE FOR SALMONELLA VIRULENCE IN MICE
DNA-REPAIR IS MORE IMPORTANT THAN CATALASE FOR SALMONELLA VIRULENCE IN MICE
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DOI：
10.1172/jci117750
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发表时间：
1995-03-01
影响因子：
15.9
通讯作者：
FANG, FC
中科院分区：
文献类型：
--
作者：
BUCHMEIER, NA;LIBBY, SJ;FANG, FC
病原微生物具有抗氧化防御机制，以保护免受活性氧代谢产物如过氧化氢（H2O2）的影响，这些代谢产物是在吞噬细胞的呼吸爆发过程中产生的。这些防御机制包括酶，如过氧化氢酶，其解毒活性氧，和DNA修复系统，其修复氧化应激引起的损伤。为了确定这两个潜在的保护性防御机制的相对重要性，对沙门氏菌感染宿主过程中遇到的氧化应激，鼠伤寒沙门氏菌双突变体不能产生的HPI或HPII过氧化氢酶的构建，并与同基因recA突变体的DNA修复缺陷进行了比较。recA突变体在体外低细胞密度下对H2O2敏感，而过氧化氢酶突变体在高细胞密度下对高H2O2浓度更敏感。发现过氧化氢酶突变体对巨噬细胞具有抗性，并保留了完整的鼠毒力，而recA突变体先前在小鼠中表现出巨噬细胞敏感性和减毒性。这些观察结果表明，沙门氏菌受到低浓度的H2O2，而在感染过程中，在相对低的细胞密度，条件需要一个完整的DNA修复系统，但没有功能性过氧化氢酶活性。
Pathogenic microorganisms possess antioxidant defense mechanisms for protection from reactive oxygen metabolites such as hydrogen peroxide (H2O2), which are generated during the respiratory burst of phagocytic cells. These defense mechanisms include enzymes such as catalase, which detoxify reactive oxygen species, and DNA repair systems which repair damage resulting from oxidative stress. To determine the relative importance of these two potentially protective defense mechanisms against oxidative stress encountered by Salmonella during infection of the host, a Salmonella typhimurium double mutant unable to produce either the HPI or HPII catalase was constructed, and compared with an isogenic recA mutant deficient in DNA repair. The recA mutant was hypersusceptible to H2O2 at low cell densities in vitro, while the catalase mutant was more susceptible to high H2O2 concentrations at high cell densities. The catalase mutant was found to be resistant to macrophages and retained full murine virulence, in contrast to the recA mutant which previously was shown to be macrophage-sensitive and attenuated in mice. These observations suggest that Salmonella is subjected to low concentrations of H2O2 while at relatively low cell density during infection, conditions requiring an intact DNA repair system but not functional catalase activity.