牛分枝杆菌 AF2122/97 PhoPR 系统的功能分析

IF 2.8 3区医学 Q3 IMMUNOLOGY

Tuberculosis Pub Date : 2024-07-14 DOI:10.1016/j.tube.2024.102544

Jose Maria Urtasun-Elizari , Ruoyao Ma , Hayleah Pickford , Damien Farrell , Gabriel Gonzalez , Viktor Perets , Chie Nakajima , Yasuhiko Suzuki , David E. MacHugh , Apoorva Bhatt , Stephen V. Gordon

{"title":"牛分枝杆菌 AF2122/97 PhoPR 系统的功能分析","authors":"Jose Maria Urtasun-Elizari , Ruoyao Ma , Hayleah Pickford , Damien Farrell , Gabriel Gonzalez , Viktor Perets , Chie Nakajima , Yasuhiko Suzuki , David E. MacHugh , Apoorva Bhatt , Stephen V. Gordon","doi":"10.1016/j.tube.2024.102544","DOIUrl":null,"url":null,"abstract":"<div>The PhoPR system is a master regulator in Mycobacterium tuberculosis. A key difference between M. tuberculosis and Mycobacterium bovis is a G71I substitution in the M. bovis PhoR orthologue. Functional studies of the M. bovis PhoPR system have generated conflicting findings, with some research suggesting that the M. bovis PhoPR is defective while others indicate it is functional.We sought to revisit the functionality of the M. bovis PhoPR system. To address this, we constructed a phoPR mutant in the reference strain M. bovis AF2122/97. We employed a combination of growth assays and transcriptomics analyses to assess the phenotype of the mutant vs wild type and complemented strains. We found that the M. bovis AF2122/97 ΔphoPR mutant showed a growth defect on solid and liquid media compared to the wild type and complemented strains. The transcriptome of the M. bovis AF2122/97 ΔphoPR mutant was also altered as compared to wild type, including differential expression of genes involved in lipid metabolism and secretion. Our work provides further insight into the activity of PhoPR in M. bovis and underlines the importance of the PhoPR system as a master regulator of gene expression in the Mycobacterium tuberculosis complex.</div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"148 ","pages":"Article 102544"},"PeriodicalIF":2.8000,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1472979224000702/pdfft?md5=02d2a9138ca63808bebfd78f2a56fe26&pid=1-s2.0-S1472979224000702-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Functional analysis of the Mycobacterium bovis AF2122/97 PhoPR system\",\"authors\":\"Jose Maria Urtasun-Elizari , Ruoyao Ma , Hayleah Pickford , Damien Farrell , Gabriel Gonzalez , Viktor Perets , Chie Nakajima , Yasuhiko Suzuki , David E. MacHugh , Apoorva Bhatt , Stephen V. Gordon\",\"doi\":\"10.1016/j.tube.2024.102544\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>The PhoPR system is a master regulator in Mycobacterium tuberculosis. A key difference between M. tuberculosis and Mycobacterium bovis is a G71I substitution in the M. bovis PhoR orthologue. Functional studies of the M. bovis PhoPR system have generated conflicting findings, with some research suggesting that the M. bovis PhoPR is defective while others indicate it is functional.We sought to revisit the functionality of the M. bovis PhoPR system. To address this, we constructed a phoPR mutant in the reference strain M. bovis AF2122/97. We employed a combination of growth assays and transcriptomics analyses to assess the phenotype of the mutant vs wild type and complemented strains. We found that the M. bovis AF2122/97 ΔphoPR mutant showed a growth defect on solid and liquid media compared to the wild type and complemented strains. The transcriptome of the M. bovis AF2122/97 ΔphoPR mutant was also altered as compared to wild type, including differential expression of genes involved in lipid metabolism and secretion. Our work provides further insight into the activity of PhoPR in M. bovis and underlines the importance of the PhoPR system as a master regulator of gene expression in the Mycobacterium tuberculosis complex.</div>\",\"PeriodicalId\":23383,\"journal\":{\"name\":\"Tuberculosis\",\"volume\":\"148 \",\"pages\":\"Article 102544\"},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2024-07-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S1472979224000702/pdfft?md5=02d2a9138ca63808bebfd78f2a56fe26&pid=1-s2.0-S1472979224000702-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Tuberculosis\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1472979224000702\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Tuberculosis","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1472979224000702","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}

引用次数: 0

摘要

PhoPR 系统是结核分枝杆菌的主调节器。结核分枝杆菌与牛分枝杆菌的一个主要区别是牛分枝杆菌 PhoR 直向同源物中的 G71I 取代。对牛分枝杆菌 PhoPR 系统的功能研究结果相互矛盾，一些研究表明牛分枝杆菌 PhoPR 存在缺陷，而另一些研究则表明其功能正常。为此，我们在参考菌株 M. bovis AF2122/97 中构建了一个 PhoPR 突变体。我们采用生长测定和转录组学分析相结合的方法来评估突变体与野生型和互补菌株的表型。我们发现，与野生型和互补型菌株相比，M. bovis AF2122/97 ΔphoPR突变体在固体和液体培养基上表现出生长缺陷。与野生型相比，M. bovis AF2122/97 ΔphoPR突变体的转录组也发生了改变，包括参与脂质代谢和分泌的基因的不同表达。我们的工作进一步揭示了 PhoPR 在牛海绵状芽孢杆菌中的活性，并强调了 PhoPR 系统作为结核分枝杆菌复合体中基因表达主调控因子的重要性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文本刊更多论文

Functional analysis of the Mycobacterium bovis AF2122/97 PhoPR system

The PhoPR system is a master regulator in Mycobacterium tuberculosis. A key difference between M. tuberculosis and Mycobacterium bovis is a G71I substitution in the M. bovis PhoR orthologue. Functional studies of the M. bovis PhoPR system have generated conflicting findings, with some research suggesting that the M. bovis PhoPR is defective while others indicate it is functional.

We sought to revisit the functionality of the M. bovis PhoPR system. To address this, we constructed a phoPR mutant in the reference strain M. bovis AF2122/97. We employed a combination of growth assays and transcriptomics analyses to assess the phenotype of the mutant vs wild type and complemented strains. We found that the M. bovis AF2122/97 ΔphoPR mutant showed a growth defect on solid and liquid media compared to the wild type and complemented strains. The transcriptome of the M. bovis AF2122/97 ΔphoPR mutant was also altered as compared to wild type, including differential expression of genes involved in lipid metabolism and secretion. Our work provides further insight into the activity of PhoPR in M. bovis and underlines the importance of the PhoPR system as a master regulator of gene expression in the Mycobacterium tuberculosis complex.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

Tuberculosis 医学-呼吸系统

CiteScore

4.60

自引率

3.10%

发文量

审稿时长

49 days

期刊介绍： Tuberculosis is a speciality journal focusing on basic experimental research on tuberculosis, notably on bacteriological, immunological and pathogenesis aspects of the disease. The journal publishes original research and reviews on the host response and immunology of tuberculosis and the molecular biology, genetics and physiology of the organism, however discourages submissions with a meta-analytical focus (for example, articles based on searches of published articles in public electronic databases, especially where there is lack of evidence of the personal involvement of authors in the generation of such material). We do not publish Clinical Case-Studies. Areas on which submissions are welcomed include: -Clinical TrialsDiagnostics- Antimicrobial resistance- Immunology- Leprosy- Microbiology, including microbial physiology- Molecular epidemiology- Non-tuberculous Mycobacteria- Pathogenesis- Pathology- Vaccine development. This Journal does not accept case-reports. The resurgence of interest in tuberculosis has accelerated the pace of relevant research and Tuberculosis has grown with it, as the only journal dedicated to experimental biomedical research in tuberculosis.