{"title":"亮氨酸对线粒体和氧化应激的影响可降低鲍曼不动杆菌的毒力和致病性。","authors":"","doi":"10.1016/j.micres.2024.127932","DOIUrl":null,"url":null,"abstract":"<div><div>Elucidating the virulence mechanisms of <em>A. baumannii</em> is essential for developing strategies to mitigate pathogenicity. Although high-virulent strains are associated with increased mortality rate in severely infected patients, the underlying mechanisms remains not well understood. Our analysis revealed leucine as a pivotal biomarker, with the <em>11d</em>P and <em>paa</em>K being significant contributors to virulence. The ATP-dependent activity and antioxidant activity were identified as the most important pathways in distinguishing the virulence of <em>A. baumannii</em>. Exogenous leucine was found to modulate mitochondria dysfunction and oxidative stress, thereby diminishing the pathogenicity of <em>A. baumannii</em> towards Beas 2B cells. Moreover, leucine reduced the virulence of <em>A. baumannii</em> to <em>Galleria mellonella</em> (<em>G. mellonella</em>) and alleviated pathological damage to lung tissues in mice. Our study offers a novel treatment strategy based on metabolomics, which may assist in the exploration and management of infections caused by highly virulent pathogens. It sets a new course for reducing the impact of highly virulent <em>A. baumannii</em> infections and has significant implications for the development of future therapeutic interventions.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":null,"pages":null},"PeriodicalIF":6.1000,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Effect of leucine on mitochondria and oxidative stress to reduce virulence and pathogenicity of Acinetobacter baumannii\",\"authors\":\"\",\"doi\":\"10.1016/j.micres.2024.127932\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Elucidating the virulence mechanisms of <em>A. baumannii</em> is essential for developing strategies to mitigate pathogenicity. Although high-virulent strains are associated with increased mortality rate in severely infected patients, the underlying mechanisms remains not well understood. Our analysis revealed leucine as a pivotal biomarker, with the <em>11d</em>P and <em>paa</em>K being significant contributors to virulence. The ATP-dependent activity and antioxidant activity were identified as the most important pathways in distinguishing the virulence of <em>A. baumannii</em>. Exogenous leucine was found to modulate mitochondria dysfunction and oxidative stress, thereby diminishing the pathogenicity of <em>A. baumannii</em> towards Beas 2B cells. Moreover, leucine reduced the virulence of <em>A. baumannii</em> to <em>Galleria mellonella</em> (<em>G. mellonella</em>) and alleviated pathological damage to lung tissues in mice. Our study offers a novel treatment strategy based on metabolomics, which may assist in the exploration and management of infections caused by highly virulent pathogens. It sets a new course for reducing the impact of highly virulent <em>A. baumannii</em> infections and has significant implications for the development of future therapeutic interventions.</div></div>\",\"PeriodicalId\":18564,\"journal\":{\"name\":\"Microbiological research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":6.1000,\"publicationDate\":\"2024-10-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Microbiological research\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0944501324003331\",\"RegionNum\":1,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Microbiological research","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0944501324003331","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MICROBIOLOGY","Score":null,"Total":0}
Effect of leucine on mitochondria and oxidative stress to reduce virulence and pathogenicity of Acinetobacter baumannii
Elucidating the virulence mechanisms of A. baumannii is essential for developing strategies to mitigate pathogenicity. Although high-virulent strains are associated with increased mortality rate in severely infected patients, the underlying mechanisms remains not well understood. Our analysis revealed leucine as a pivotal biomarker, with the 11dP and paaK being significant contributors to virulence. The ATP-dependent activity and antioxidant activity were identified as the most important pathways in distinguishing the virulence of A. baumannii. Exogenous leucine was found to modulate mitochondria dysfunction and oxidative stress, thereby diminishing the pathogenicity of A. baumannii towards Beas 2B cells. Moreover, leucine reduced the virulence of A. baumannii to Galleria mellonella (G. mellonella) and alleviated pathological damage to lung tissues in mice. Our study offers a novel treatment strategy based on metabolomics, which may assist in the exploration and management of infections caused by highly virulent pathogens. It sets a new course for reducing the impact of highly virulent A. baumannii infections and has significant implications for the development of future therapeutic interventions.
期刊介绍:
Microbiological Research is devoted to publishing reports on prokaryotic and eukaryotic microorganisms such as yeasts, fungi, bacteria, archaea, and protozoa. Research on interactions between pathogenic microorganisms and their environment or hosts are also covered.