{"title":"Identification of Poly(ADP-ribose) Polymerase 9 (PARP9) as a Potent Suppressor for <i>Mycobacterium tuberculosis</i> Infection.","authors":"Zhenyu Zhu, Shufeng Weng, Fen Zheng, Qi Zhao, Ying Xu, Jiaxue Wu","doi":"10.1007/s43657-023-00112-2","DOIUrl":null,"url":null,"abstract":"<p><p>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 in <i>Mycobacterium</i> infection 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 during <i>Mycobacterium</i> infection were validated in Tohoku Hospital Pediatrics-1 (THP1)-induced differentiated macrophages infected with <i>Mycobacterium</i> model strains bacillus Calmette-Guérin (BCG) and in human lung adenocarcinoma A549 cells infected with <i>Mycobacterium smegmatis</i> (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 during <i>Mycobacterium</i> infection. In addition, the biological function of host PARP9 in <i>Mycobacterium</i> infection 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 during <i>Mycobacterium</i> infection and provides evidence supporting PARP9 as a potent suppressor for <i>Mycobacterium</i> infection.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43657-023-00112-2.</p>","PeriodicalId":20318,"journal":{"name":"Plant Phenomics","volume":null,"pages":null},"PeriodicalIF":7.6000,"publicationDate":"2023-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11169154/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Plant Phenomics","FirstCategoryId":"97","ListUrlMain":"https://doi.org/10.1007/s43657-023-00112-2","RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/4/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"AGRONOMY","Score":null,"Total":0}
引用次数: 0
Abstract
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 in Mycobacterium infection 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 during Mycobacterium infection were validated in Tohoku Hospital Pediatrics-1 (THP1)-induced differentiated macrophages infected with Mycobacterium model strains bacillus Calmette-Guérin (BCG) and in human lung adenocarcinoma A549 cells infected with Mycobacterium 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 during Mycobacterium infection. In addition, the biological function of host PARP9 in Mycobacterium infection 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 during Mycobacterium infection and provides evidence supporting PARP9 as a potent suppressor for Mycobacterium infection.
Supplementary information: The online version contains supplementary material available at 10.1007/s43657-023-00112-2.
期刊介绍:
Plant Phenomics is an Open Access journal published in affiliation with the State Key Laboratory of Crop Genetics & Germplasm Enhancement, Nanjing Agricultural University (NAU) and published by the American Association for the Advancement of Science (AAAS). Like all partners participating in the Science Partner Journal program, Plant Phenomics is editorially independent from the Science family of journals.
The mission of Plant Phenomics is to publish novel research that will advance all aspects of plant phenotyping from the cell to the plant population levels using innovative combinations of sensor systems and data analytics. Plant Phenomics aims also to connect phenomics to other science domains, such as genomics, genetics, physiology, molecular biology, bioinformatics, statistics, mathematics, and computer sciences. Plant Phenomics should thus contribute to advance plant sciences and agriculture/forestry/horticulture by addressing key scientific challenges in the area of plant phenomics.
The scope of the journal covers the latest technologies in plant phenotyping for data acquisition, data management, data interpretation, modeling, and their practical applications for crop cultivation, plant breeding, forestry, horticulture, ecology, and other plant-related domains.