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首页> 外文期刊>Journal of bacteriology >Iron Storage Proteins Are Essential for the Survival and Pathogenesis of Mycobacterium tuberculosis in THP-1 Macrophages and the Guinea Pig Model of Infection
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Iron Storage Proteins Are Essential for the Survival and Pathogenesis of Mycobacterium tuberculosis in THP-1 Macrophages and the Guinea Pig Model of Infection

机译：铁存储蛋白对于THP-1巨噬细胞和豚鼠感染模型中结核分枝杆菌的生存和发病机制至关重要。

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摘要

Iron is one of the crucial elements required for the growth of Mycobacterium tuberculosis. However, excess free iron becomes toxic for the cells because it catalyzes the production of reactive oxygen radicals, leading to oxidative damage. Hence, it is essential for the pathogen to have the ability to store intracellular iron in an iron-rich environment and utilize it under iron depletion. M. tuberculosis has two iron storage proteins, namely BfrA (Rv1876; a bacterioferritin) and BfrB (Rv3841; a ferritin-like protein). However, the demonstration of biological significance requires the disruption of relevant genes and the evaluation of the resulting mutant for its ability to survive in the host and cause disease. In this study, we have disrupted bfrA and bfrB of M. tuberculosis and demonstrated that these genes are crucial for the storage and supply of iron for the growth of bacteria and to withstand oxidative stress in vitro. In addition, the bfrA bfrB double mutant (H37Rv ΔbfrA ΔbfrB) exhibited a marked reduction in its ability to survive inside human macrophages. Guinea pigs infected with H37Rv ΔbfrA ΔbfrB exhibited a marked diminution in the dissemination of the bacilli to spleen compared to that of the parental strain. Moreover, guinea pigs infected with H37Rv ΔbfrA ΔbfrB exhibited significantly reduced pathological damage in spleen and lungs compared to that of animals infected with the parental strain. Our study clearly demonstrates the importance of these iron storage proteins in the survival and pathogenesis of M. tuberculosis in the host and establishes them as attractive targets for the development of new inhibitors against mycobacterial infections.
机译：铁是结核分枝杆菌生长所需的关键元素之一。但是，过量的游离铁对细胞具有毒性，因为它催化了活性氧自由基的产生，从而导致氧化损伤。因此，病原体必须具有在富铁环境中储存细胞内铁并在铁耗竭下利用它的能力。结核分枝杆菌具有两种铁存储蛋白，即BfrA（Rv1876;细菌铁蛋白）和BfrB（Rv3841;铁蛋白样蛋白）。然而，生物学意义的证明要求破坏相关基因并评估所得突变体在宿主中存活并引起疾病的能力。在这项研究中，我们破坏了结核分枝杆菌的 bfrA 和 bfrB 并证明了这些基因对于铁的储存和供应对于细菌的生长和抵抗至关重要。体外氧化应激。此外， bfrA bfrB 双突变体（H37RvΔ bfrA Δ bfrB ）在人类巨噬细胞中的存活能力显着降低。与亲本菌株相比，感染了H37RvΔ bfrA Δ bfrB 的豚鼠的细菌向脾脏的传播显着减少。此外，感染H37RvΔ bfrA Δ bfrB 的豚鼠与感染亲本菌株的动物相比，脾脏和肺部的病理损伤显着降低。我们的研究清楚地证明了这些铁存储蛋白在宿主中结核分枝杆菌的存活和发病机理中的重要性，并将它们确定为开发针对分枝杆菌感染的新型抑制剂的有吸引力的靶标。

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