Identification of Poly(ADP-ribose) Polymerase 9 (PARP9) as a Potent Suppressor for Mycobacterium tuberculosis Infection
Identification of Poly(ADP-ribose) Polymerase 9 (PARP9) as a Potent Suppressor for Mycobacterium tuberculosis Infection
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DOI：
10.1007/s43657-023-00112-2
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发表时间：
2023-09-04
期刊：
影响因子：
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通讯作者：
Wu，Jiaxue
中科院分区：
文献类型：
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作者：
Zhu，Zhenyu;Weng，Shufeng;Wu，Jiaxue
ADP-核糖基化是由ADP-核糖基转移酶（ART）介导的可逆和动态的翻译后修饰。聚ADP-核糖聚合酶（Poly（ADP-ribose）polymerases，PARP）是人类ART的一个重要家族。ADP-核糖基化和PARP在宿主-病原体相互作用中具有重要作用，特别是在病毒感染中。然而，ADP-核糖基化和PARP在分枝杆菌感染中的功能和潜在的分子机制尚不清楚。在这项研究中，生物信息学分析显示，与健康个体相比，结核病患者中几种PARP的表达水平发生了显着变化。此外，这些PARP的表达水平在结核病治疗后恢复正常。然后，分别在感染分枝杆菌模型菌株卡介苗（BCG）的东北医院儿科-1（THP 1）诱导分化的巨噬细胞和感染耻垢分枝杆菌（Ms）的人肺腺癌A549细胞中验证了分枝杆菌感染期间PARP表达水平的变化。在感染过程中，PARP 9、PARP 10、PARP 12和PARP 14的mRNA水平显著升高，蛋白水平也相应升高，表明这些PARP在分枝杆菌感染过程中可能具有生物学功能。此外，还进一步研究了宿主PARP 9在分枝杆菌感染中的生物学功能。PARP 9缺陷显著增加MS的感染效率和细胞内增殖能力，这被PARP 9的重建逆转。总之，本研究更新了对分枝杆菌感染过程中PARP表达变化的理解，并提供了支持PARP 9作为分枝杆菌感染的有效抑制因子的证据。
ADP-ribosylation is a reversible and dynamic post-translational modification mediated by ADP-ribosyltransferases (ARTs). Poly(ADP-ribose) polymerases (PARPs) are an important family of human ARTs. ADP-ribosylation and PARPs have crucial functions in host–pathogen interaction, especially in viral infections. However, the functions and potential molecular mechanisms of ADP-ribosylation and PARPs inMycobacteriuminfection remain unknown. In this study, bioinformatics analysis revealed significantly changed expression levels of several PARPs in tuberculosis patients compared to healthy individuals. Moreover, the expression levels of these PARPs returned to normal following tuberculosis treatment. Then, the changes in the expression levels of PARPs duringMycobacteriuminfection were validated in Tohoku Hospital Pediatrics-1 (THP1)-induced differentiated macrophages infected withMycobacteriummodel strains bacillus Calmette-Guérin (BCG) and in human lung adenocarcinoma A549 cells infected withMycobacterium smegmatis(Ms), respectively. The mRNA levels of PARP9, PARP10, PARP12, and PARP14 were most significantly increased during infection, with corresponding increases in protein levels, indicating the possible biological functions of these PARPs duringMycobacteriuminfection. In addition, the biological function of host PARP9 inMycobacteriuminfection was further studied. PARP9 deficiency significantly increased the infection efficiency and intracellular proliferation ability of Ms, which was reversed by the reconstruction of PARP9. Collectively, this study updates the understanding of changes in PARP expression duringMycobacteriuminfection and provides evidence supporting PARP9 as a potent suppressor forMycobacteriuminfection.