Myricanol Inhibits the Type III Secretion System of Salmonella enterica Serovar Typhimurium by Interfering With the DNA-Binding Activity of HilD.
Identifieur interne : 000102 ( Main/Exploration ); précédent : 000101; suivant : 000103Myricanol Inhibits the Type III Secretion System of Salmonella enterica Serovar Typhimurium by Interfering With the DNA-Binding Activity of HilD.
Auteurs : Yang Wu [République populaire de Chine] ; Xuefei Yang [République populaire de Chine] ; Dongdong Zhang [République populaire de Chine] ; Chunhua Lu [République populaire de Chine]Source :
- Frontiers in microbiology [ 1664-302X ] ; 2020.
Abstract
The type III secretion system (T3SS) consists of a syringe-like export machine injecting effectors from the bacterial cytosol directly into host cells to establish infection. This mechanism is widely distributed in gram-negative bacteria and can be targeted as an innovative strategy for the developing of anti-virulence drugs. In this study, we present an effective T3SS inhibitor, myricanol, inspired by the use of folk medicinal plants traditionally used against infections. Myricanol is a cyclic diarylheptanoid isolated from the medicinal plant Myrica nagi, which is found in South and East Asia. Bioassay-guided fractionation revealed that myricanol inhibited not only the secretion of type III effector proteins of Salmonella enterica serovar Typhimurium UK-1 χ8956 (S. Typhimurium) but also the invasion of S. Typhimurium into mammalian cells, but showed no toxicity to bacterial growth or the host cells. RNA-Seq data analysis showed that the transcription of the pathogenesis-related SPI-1 gene was significantly inhibited by myricanol. Further study demonstrated that myricanol binds physically to HilD and interferes with its DNA-binding activity to the promoters of the hilA and invF genes. In conclusion, we propose that myricanol is responsible for the anti-infectious properties of M. nagi and is a novel T3SS inhibitor of S. Typhimurium through a previously unappreciated mechanism of action.
DOI: 10.3389/fmicb.2020.571217
PubMed: 33101243
PubMed Central: PMC7546796
Affiliations:
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Biology, Ministry of Education, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan</wicri:regionArea><wicri:noRegion>Jinan</wicri:noRegion></affiliation></author><author><name sortKey="Yang, Xuefei" sort="Yang, Xuefei" uniqKey="Yang X" first="Xuefei" last="Yang">Xuefei Yang</name><affiliation wicri:level="1"><nlm:affiliation>Key Laboratory of Economic Plants and Biotechnology, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Economic Plants and Biotechnology, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming</wicri:regionArea><wicri:noRegion>Kunming</wicri:noRegion></affiliation></author><author><name sortKey="Zhang, Dongdong" sort="Zhang, Dongdong" uniqKey="Zhang D" first="Dongdong" last="Zhang">Dongdong Zhang</name><affiliation wicri:level="1"><nlm:affiliation>Key Laboratory of Economic Plants and Biotechnology, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Economic Plants and Biotechnology, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming</wicri:regionArea><wicri:noRegion>Kunming</wicri:noRegion></affiliation></author><author><name sortKey="Lu, Chunhua" sort="Lu, Chunhua" uniqKey="Lu C" first="Chunhua" last="Lu">Chunhua Lu</name><affiliation wicri:level="1"><nlm:affiliation>Key Laboratory of Chemical Biology, Ministry of Education, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Chemical Biology, Ministry of Education, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan</wicri:regionArea><wicri:noRegion>Jinan</wicri:noRegion></affiliation></author></analytic><series><title level="j">Frontiers in microbiology</title><idno type="ISSN">1664-302X</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The type III secretion system (T3SS) consists of a syringe-like export machine injecting effectors from the bacterial cytosol directly into host cells to establish infection. This mechanism is widely distributed in gram-negative bacteria and can be targeted as an innovative strategy for the developing of anti-virulence drugs. In this study, we present an effective T3SS inhibitor, myricanol, inspired by the use of folk medicinal plants traditionally used against infections. Myricanol is a cyclic diarylheptanoid isolated from the medicinal plant <i>Myrica nagi</i>, which is found in South and East Asia. Bioassay-guided fractionation revealed that myricanol inhibited not only the secretion of type III effector proteins of <i>Salmonella enterica</i> serovar Typhimurium UK-1 χ8956 (<i>S</i>. Typhimurium) but also the invasion of <i>S</i>. Typhimurium into mammalian cells, but showed no toxicity to bacterial growth or the host cells. RNA-Seq data analysis showed that the transcription of the pathogenesis-related SPI-1 gene was significantly inhibited by myricanol. Further study demonstrated that myricanol binds physically to HilD and interferes with its DNA-binding activity to the promoters of the <i>hilA</i> and <i>invF</i> genes. In conclusion, we propose that myricanol is responsible for the anti-infectious properties of <i>M. nagi</i> and is a novel T3SS inhibitor of <i>S</i>. Typhimurium through a previously unappreciated mechanism of action.</div></front></TEI><pubmed><MedlineCitation Status="PubMed-not-MEDLINE" Owner="NLM"><PMID Version="1">33101243</PMID><DateRevised><Year>2020</Year><Month>10</Month><Day>28</Day></DateRevised><Article PubModel="Electronic-eCollection"><Journal><ISSN IssnType="Print">1664-302X</ISSN><JournalIssue CitedMedium="Print"><Volume>11</Volume><PubDate><Year>2020</Year></PubDate></JournalIssue><Title>Frontiers in microbiology</Title><ISOAbbreviation>Front Microbiol</ISOAbbreviation></Journal><ArticleTitle>Myricanol Inhibits the Type III Secretion System of <i>Salmonella enterica</i> Serovar Typhimurium by Interfering With the DNA-Binding Activity of HilD.</ArticleTitle><Pagination><MedlinePgn>571217</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.3389/fmicb.2020.571217</ELocationID><Abstract><AbstractText>The type III secretion system (T3SS) consists of a syringe-like export machine injecting effectors from the bacterial cytosol directly into host cells to establish infection. This mechanism is widely distributed in gram-negative bacteria and can be targeted as an innovative strategy for the developing of anti-virulence drugs. In this study, we present an effective T3SS inhibitor, myricanol, inspired by the use of folk medicinal plants traditionally used against infections. Myricanol is a cyclic diarylheptanoid isolated from the medicinal plant <i>Myrica nagi</i>, which is found in South and East Asia. Bioassay-guided fractionation revealed that myricanol inhibited not only the secretion of type III effector proteins of <i>Salmonella enterica</i> serovar Typhimurium UK-1 χ8956 (<i>S</i>. Typhimurium) but also the invasion of <i>S</i>. Typhimurium into mammalian cells, but showed no toxicity to bacterial growth or the host cells. RNA-Seq data analysis showed that the transcription of the pathogenesis-related SPI-1 gene was significantly inhibited by myricanol. Further study demonstrated that myricanol binds physically to HilD and interferes with its DNA-binding activity to the promoters of the <i>hilA</i> and <i>invF</i> genes. In conclusion, we propose that myricanol is responsible for the anti-infectious properties of <i>M. nagi</i> and is a novel T3SS inhibitor of <i>S</i>. Typhimurium through a previously unappreciated mechanism of action.</AbstractText><CopyrightInformation>Copyright © 2020 Wu, Yang, Zhang and Lu.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Wu</LastName><ForeName>Yang</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Key Laboratory of Chemical Biology, Ministry of Education, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yang</LastName><ForeName>Xuefei</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>Key Laboratory of Economic Plants and Biotechnology, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Dongdong</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Key Laboratory of Economic Plants and Biotechnology, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lu</LastName><ForeName>Chunhua</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Key Laboratory of Chemical Biology, Ministry of Education, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>09</Month><Day>25</Day></ArticleDate></Article><MedlineJournalInfo><Country>Switzerland</Country><MedlineTA>Front Microbiol</MedlineTA><NlmUniqueID>101548977</NlmUniqueID><ISSNLinking>1664-302X</ISSNLinking></MedlineJournalInfo><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">HilD</Keyword><Keyword MajorTopicYN="N">Salmonella</Keyword><Keyword 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Wu</name></noRegion><name sortKey="Lu, Chunhua" sort="Lu, Chunhua" uniqKey="Lu C" first="Chunhua" last="Lu">Chunhua Lu</name><name sortKey="Yang, Xuefei" sort="Yang, Xuefei" uniqKey="Yang X" first="Xuefei" last="Yang">Xuefei Yang</name><name sortKey="Zhang, Dongdong" sort="Zhang, Dongdong" uniqKey="Zhang D" first="Dongdong" last="Zhang">Dongdong Zhang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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