Mycobacterium tuberculosis catalase and peroxidase activities and resistance to oxidative killing in human monocytes in vitro
Mycobacterium tuberculosis catalase and peroxidase activities and resistance to oxidative killing in human monocytes in vitro
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DOI：
10.1128/iai.67.1.74-79.1999
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发表时间：
1999-01-01
影响因子：
3.1
通讯作者：
Kaplan, G
中科院分区：
文献类型：
--
作者：
Manca, C;Paul, S;Kaplan, G
结核分枝杆菌对过氧化氢和有机过氧化物具有较高的抵抗力，耐药谱由分枝杆菌过氧化氢酶-过氧化物酶（KatG）介导，也可能由烷基过氧化氢还原酶（AhpC）介导。我们检测了一个实验室菌株、两个临床分离株和三个重组M.结核病与不同水平的KatG和AhpC。其中5株分枝杆菌的胞内怀疑时间为27 ~ 32 h，而1株KatG缺陷型临床分离株的胞内怀疑时间为27 ~ 32 h，（ATCC 35825）在类似于76小时内加倍，通过外源添加的H2 O2对分枝杆菌的杀伤对于细胞内杆菌比对于来源于破坏的单核细胞的那些杆菌更显著，菌株，即使没有检测到KatG表达或过氧化氢酶活性，也对外源H2 O2的杀伤相对敏感（43 - 67%杀伤）。然而，即使是最小的过氧化氢酶活性存在，分枝杆菌过氧化氢酶活性超过10倍的范围（0.56至6.2 U/mg）与85%的杆菌的生存。过氧化物酶活性水平与分枝杆菌菌株对H2 O2介导的杀伤的抗性显著相关。通过4 β-佛波醇12 β-肉豆蔻酸酯13 α-乙酸酯处理感染的单核细胞的内源性氧化爆发诱导降低了KatG无效菌株（H37 Rv Inh（r））的活力，但不降低KatG过表达菌株[H37 Rv（pMH 59）]的活力。这些结果表明，分枝杆菌对氧化代谢产物（包括H2 O2和其他过氧化物）的抗性可能是宿主吞噬细胞内细菌存活的重要机制。
Mycobacterium tuberculosis has a relatively high resistance to killing by hydrogen peroxide and organic peroxides, Resistance map be mediated by mycobacterial catalase-peroxidase (KatG) and possibly by alkyl hydroperoxide reductase (AhpC), To determine the interrelationship between sensitivity to H2O2, catalase and peroxidase activities, and bacillary growth rates measured bath intracellularly in human monocytes and in culture medium, we examined one laboratory strain, two clinical isolates, and three recombinant strains of M. tuberculosis with differing levels of KatG and AhpC. Five of the mycobacterial strains had intracellular doubting times of 27 to 32 h, while one KatG-deficient clinical isolate (ATCC 35825) doubled in similar to 76 h, Killing of mycobacteria by exogenously added H2O2 was more pronounced for intracellular bacilli than for those bacilli derived from disrupted monocytes, Strains,vith no detectable KatG expression or catalase activity were relatively sensitive to killing (43 to 67% killing) by exogenous H2O2. However, once even minimal catalase activity was present, mycobacterial catalase activity over a 10-fold range (0.56 to 6.2 U/mg) was associated with survival of 85% of the bacilli. Peroxidase activity levels correlated significantly with resistance of the mycobacterial strains to H2O2-mediated killing. An endogenous oxidative burst induction by 4 beta-phorbol 12 beta-myristate 13 alpha-acetate treatment of infected monocytes reduced the viability of the KatG null strain (H37Rv Inh(r)) but not the KatG-overespressing strain [H37Rv(pMH59)]. These results suggest that mycobacterial resistance to oxidative metabolites (including H2O2 and other peroxides) may be an important mechanism of bacillary survival within the host phagocyte.