Jaeger Timo
MOLISA GmbH, Molecular Links Sachsen-Anhalt, Magdeburg, Germany.
Subcell Biochem. 2007;44:207-17. doi: 10.1007/978-1-4020-6051-9_9.
Like other actinomycetes Mycobacterium tuberculosis lacks glutathione and, consequently, the glutathione peroxidases that dominate the antioxidant defence of its mammalian hosts. The hydrogen peroxide metabolism of the pathogen has for long been recognised to depend on a heme-containing catalase/peroxidase. Clinical isolates lacking the catalase were virulent and proved to be resistant to the first line tuberculostatic isoniazid, because the enzyme is evidently required to activate this drug. The survival and virulence of such strains are attributed to the peroxiredoxin-type peroxidases alkyl hydroperoxide reductase (AhpC) and thioredoxin peroxidase (TPx). The most common AhpC reductant in bacteria, the disulfide reductase AhpF, is deleted in M. tuberculosis. Instead, AhpC can be reduced by AhpD, a CXXC-motif-containing protein, or by one of the mycobacterial thioredoxins, TrxC. TPx is reduced by thioredoxins B and C. Mycobacteria contain three more peroxiredoxins, the 1-Cys-Prx AhpE, Bcp and BcpB, whose function and reductants are still unknown.
与其他放线菌一样，结核分枝杆菌缺乏谷胱甘肽，因此也缺乏在其哺乳动物宿主的抗氧化防御中占主导地位的谷胱甘肽过氧化物酶。长期以来，人们一直认为该病原体的过氧化氢代谢依赖于一种含血红素的过氧化氢酶/过氧化物酶。缺乏过氧化氢酶的临床分离株具有毒性，并被证明对一线抗结核药物异烟肼耐药，因为该酶显然是激活这种药物所必需的。此类菌株的存活和毒性归因于过氧化物酶体增殖物激活受体（Prx）型过氧化物酶烷基过氧化氢还原酶（AhpC）和硫氧还蛋白过氧化物酶（TPx）。细菌中最常见的AhpC还原剂——二硫键还原酶AhpF，在结核分枝杆菌中缺失。相反，AhpC可以被AhpD（一种含有CXXC基序的蛋白质）或分枝杆菌硫氧还蛋白之一TrxC还原。TPx由硫氧还蛋白B和C还原。分枝杆菌还含有另外三种过氧化物酶体增殖物激活受体，即1-Cys-Prx AhpE、Bcp和BcpB，其功能和还原剂仍然未知。
