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首页> 外文期刊>Infection and immunity >Deficiency of Double-Strand DNA Break Repair Does Not Impair Mycobacterium tuberculosis Virulence in Multiple Animal Models of Infection
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Deficiency of Double-Strand DNA Break Repair Does Not Impair Mycobacterium tuberculosis Virulence in Multiple Animal Models of Infection

机译：双链DNA断裂修复的缺陷并不损害多种感染动物模型中的结核分枝杆菌毒力。

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Mycobacterium tuberculosis persistence within its human host requires mechanisms to resist the effector molecules of host immunity, which exert their bactericidal effects through damaging pathogen proteins, membranes, and DNA. Substantial evidence indicates that bacterial pathogens, including M. tuberculosis, require DNA repair systems to repair the DNA damage inflicted by the host during infection, but the role of double-strand DNA break (DSB) repair systems is unclear. Double-strand DNA breaks are the most cytotoxic form of DNA damage and must be repaired for chromosome replication to proceed. M. tuberculosis elaborates three genetically distinct DSB repair systems: homologous recombination (HR), nonhomologous end joining (NHEJ), and single-strand annealing (SSA). NHEJ, which repairs DSBs in quiescent cells, may be particularly relevant to M. tuberculosis latency. However, very little information is available about the phenotype of DSB repair-deficient M. tuberculosis in animal models of infection. Here we tested M. tuberculosis strains lacking NHEJ (a Δku ΔligD strain), HR (a ΔrecA strain), or both (a ΔrecA Δku strain) in C57BL/6J mice, C3HeB/FeJ mice, guinea pigs, and a mouse hollow-fiber model of infection. We found no difference in bacterial load, histopathology, or host mortality between wild-type and DSB repair mutant strains in any model of infection. These results suggest that the animal models tested do not inflict DSBs on the mycobacterial chromosome, that other repair pathways can compensate for the loss of NHEJ and HR, or that DSB repair is not required for M. tuberculosis pathogenesis.
机译：结核分枝杆菌在其人类宿主中的持久性需要机制来抵抗宿主免疫的效应分子，该分子通过破坏病原体蛋白质，膜和DNA发挥杀菌作用。大量证据表明，细菌病原体（包括结核分枝杆菌）需要DNA修复系统来修复宿主在感染过程中造成的DNA损伤，但双链DNA断裂（DSB）修复系统的作用尚不清楚。双链DNA断裂是DNA损伤的最具细胞毒性形式，必须进行修复才能进行染色体复制。结核分枝杆菌详细阐述了三种在基因上不同的DSB修复系统：同源重组（HR），非同源末端连接（NHEJ）和单链退火（SSA）。 NHEJ修复静态细胞中的DSB，可能与结核分枝杆菌潜伏期特别相关。但是，在感染的动物模型中，关于DSB修复缺陷型结核分枝杆菌表型的信息很少。在这里，我们测试了缺乏NHEJ（Δ ku Δ ligD 菌株），HR（Δ recA 菌株）或两者均缺乏的结核分枝杆菌菌株（ C57BL / 6J小鼠，C3HeB / FeJ小鼠，豚鼠和小鼠中空纤维感染模型中的Δ recA Δ ku 株）。我们发现在任何感染模型中，野生型和DSB修复突变株之间的细菌载量，组织病理学或宿主死亡率均无差异。这些结果表明，所测试的动物模型不会在分枝杆菌染色体上造成DSB，其他修复途径可以补偿NHEJ和HR的损失，或者结核分枝杆菌发病机理不需要DSB修复。

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