{"title":"金黄色葡萄球菌的 NAD 激酶是包膜和抗生素应激反应所必需的。","authors":"Clarisse Leseigneur , Lou Mondange , Javier Pizarro-Cerdá , Olivier Dussurget","doi":"10.1016/j.micinf.2024.105334","DOIUrl":null,"url":null,"abstract":"<div><p>Global burden of infectious diseases and antimicrobial resistance are major public health issues calling for innovative control measures. Bacterial NAD kinase (NADK) is a crucial enzyme for production of NADP(H) and growth. In <em>Staphylococcus aureus</em>, NADK promotes pathogenesis by supporting production of key virulence determinants. Here, we find that knockdown of NADK by CRISPR interference sensitizes <em>S. aureus</em> to osmotic stress and to stresses induced by antibiotics targeting the envelop as well as replication, transcription and translation. Thus, NADK represents a promising target for the development of inhibitors which could be used in combination with current antibiotics.</p></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":null,"pages":null},"PeriodicalIF":2.6000,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1286457924000649/pdfft?md5=3fdb489c47a431eb7cdb27b2783f5aea&pid=1-s2.0-S1286457924000649-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Staphylococcus aureus NAD kinase is required for envelop and antibiotic stress responses\",\"authors\":\"Clarisse Leseigneur , Lou Mondange , Javier Pizarro-Cerdá , Olivier Dussurget\",\"doi\":\"10.1016/j.micinf.2024.105334\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Global burden of infectious diseases and antimicrobial resistance are major public health issues calling for innovative control measures. Bacterial NAD kinase (NADK) is a crucial enzyme for production of NADP(H) and growth. In <em>Staphylococcus aureus</em>, NADK promotes pathogenesis by supporting production of key virulence determinants. Here, we find that knockdown of NADK by CRISPR interference sensitizes <em>S. aureus</em> to osmotic stress and to stresses induced by antibiotics targeting the envelop as well as replication, transcription and translation. Thus, NADK represents a promising target for the development of inhibitors which could be used in combination with current antibiotics.</p></div>\",\"PeriodicalId\":18497,\"journal\":{\"name\":\"Microbes and Infection\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2024-05-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S1286457924000649/pdfft?md5=3fdb489c47a431eb7cdb27b2783f5aea&pid=1-s2.0-S1286457924000649-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Microbes and Infection\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1286457924000649\",\"RegionNum\":4,\"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":"Microbes and Infection","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1286457924000649","RegionNum":4,"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
全球传染病负担和抗菌药耐药性是重大的公共卫生问题,需要采取创新的控制措施。细菌 NAD 激酶(NADK)是产生 NADP(H)和生长的关键酶。在金黄色葡萄球菌中,NADK 通过支持关键毒力决定因子的产生来促进致病机理。在这里,我们发现通过 CRISPR 干扰敲除 NADK 会使金黄色葡萄球菌对渗透压和针对包膜以及复制、转录和翻译的抗生素诱导的压力敏感。因此,NADK是开发抑制剂的一个有希望的靶点,可与现有抗生素联合使用。
Staphylococcus aureus NAD kinase is required for envelop and antibiotic stress responses
Global burden of infectious diseases and antimicrobial resistance are major public health issues calling for innovative control measures. Bacterial NAD kinase (NADK) is a crucial enzyme for production of NADP(H) and growth. In Staphylococcus aureus, NADK promotes pathogenesis by supporting production of key virulence determinants. Here, we find that knockdown of NADK by CRISPR interference sensitizes S. aureus to osmotic stress and to stresses induced by antibiotics targeting the envelop as well as replication, transcription and translation. Thus, NADK represents a promising target for the development of inhibitors which could be used in combination with current antibiotics.
期刊介绍:
Microbes and Infection publishes 10 peer-reviewed issues per year in all fields of infection and immunity, covering the different levels of host-microbe interactions, and in particular:
the molecular biology and cell biology of the crosstalk between hosts (human and model organisms) and microbes (viruses, bacteria, parasites and fungi), including molecular virulence and evasion mechanisms.
the immune response to infection, including pathogenesis and host susceptibility.
emerging human infectious diseases.
systems immunology.
molecular epidemiology/genetics of host pathogen interactions.
microbiota and host "interactions".
vaccine development, including novel strategies and adjuvants.
Clinical studies, accounts of clinical trials and biomarker studies in infectious diseases are within the scope of the journal.
Microbes and Infection publishes articles on human pathogens or pathogens of model systems. However, articles on other microbes can be published if they contribute to our understanding of basic mechanisms of host-pathogen interactions. Purely descriptive and preliminary studies are discouraged.