RapamycinFungusV1, Main, Exploration, bibRecord, 001339

Azithromycin blocks autophagy and may predispose cystic fibrosis patients to mycobacterial infection.

Identifieur interne : 001339 ( Main/Exploration ); précédent : 001338; suivant : 001340

Azithromycin blocks autophagy and may predispose cystic fibrosis patients to mycobacterial infection.

Auteurs : Maurizio Renna [Royaume-Uni] ; Catherine Schaffner ; Karen Brown ; Shaobin Shang ; Marcela Henao Tamayo ; Krisztina Hegyi ; Neil J. Grimsey ; David Cusens ; Sarah Coulter ; Jason Cooper ; Anne R. Bowden ; Sandra M. Newton ; Beate Kampmann ; Jennifer Helm ; Andrew Jones ; Charles S. Haworth ; Randall J. Basaraba ; Mary Ann Degroote ; Diane J. Ordway ; David C. Rubinsztein ; R Andres Floto

Source :

The Journal of clinical investigation [ 1558-8238 ] ; 2011.

RBID : pubmed:21804191

Descripteurs français

KwdFr :
- Adulte (MeSH), Animaux (MeSH), Antibactériens (effets indésirables), Antibactériens (pharmacologie), Antibactériens (usage thérapeutique), Antienzymes (pharmacologie), Autophagie (effets des médicaments et des substances chimiques), Azithromycine (effets indésirables), Azithromycine (pharmacologie), Azithromycine (usage thérapeutique), Cellules COS (MeSH), Cellules HeLa (MeSH), Humains (MeSH), Infections à Mycobacterium (microbiologie), Infections à Mycobacterium (étiologie), Lysosomes (métabolisme), Macrolides (pharmacologie), Macrophages (cytologie), Macrophages (effets des médicaments et des substances chimiques), Macrophages (microbiologie), Mucoviscidose (complications), Mucoviscidose (microbiologie), Mucoviscidose (traitement médicamenteux), Mycobacterium (effets des médicaments et des substances chimiques), Mycobacterium (pathogénicité), Mycobacterium (physiologie), Phagosomes (effets des médicaments et des substances chimiques), Phagosomes (métabolisme), Protéines associées aux microtubules (génétique), Protéines associées aux microtubules (métabolisme), Protéines de fusion recombinantes (génétique), Protéines de fusion recombinantes (métabolisme), Résistance bactérienne aux médicaments (MeSH), Sirolimus (pharmacologie), Souris (MeSH), Souris de lignée C57BL (MeSH).
MESH :
- cytologie : Macrophages.
- effets des médicaments et des substances chimiques : Autophagie, Macrophages, Mycobacterium, Phagosomes.
- effets indésirables : Antibactériens, Azithromycine, Mucoviscidose.
- génétique : Protéines associées aux microtubules, Protéines de fusion recombinantes.
- microbiologie : Infections à Mycobacterium, Macrophages, Mucoviscidose.
- métabolisme : Lysosomes, Phagosomes, Protéines associées aux microtubules, Protéines de fusion recombinantes.
- pathogénicité : Mycobacterium.
- pharmacologie : Antibactériens, Antienzymes, Azithromycine, Macrolides, Sirolimus.
- physiologie : Mycobacterium.
- traitement médicamenteux : Mucoviscidose.
- usage thérapeutique : Antibactériens, Azithromycine.
- étiologie : Infections à Mycobacterium.
- Adulte, Animaux, Cellules COS, Cellules HeLa, Humains, Résistance bactérienne aux médicaments, Souris, Souris de lignée C57BL.

English descriptors

KwdEn :
- Adult (MeSH), Animals (MeSH), Anti-Bacterial Agents (adverse effects), Anti-Bacterial Agents (pharmacology), Anti-Bacterial Agents (therapeutic use), Autophagy (drug effects), Azithromycin (adverse effects), Azithromycin (pharmacology), Azithromycin (therapeutic use), COS Cells (MeSH), Chlorocebus aethiops (MeSH), Cystic Fibrosis (complications), Cystic Fibrosis (drug therapy), Cystic Fibrosis (microbiology), Drug Resistance, Bacterial (MeSH), Enzyme Inhibitors (pharmacology), HeLa Cells (MeSH), Humans (MeSH), Lysosomes (metabolism), Macrolides (pharmacology), Macrophages (cytology), Macrophages (drug effects), Macrophages (microbiology), Mice (MeSH), Mice, Inbred C57BL (MeSH), Microtubule-Associated Proteins (genetics), Microtubule-Associated Proteins (metabolism), Mycobacterium (drug effects), Mycobacterium (pathogenicity), Mycobacterium (physiology), Mycobacterium Infections (etiology), Mycobacterium Infections (microbiology), Phagosomes (drug effects), Phagosomes (metabolism), Recombinant Fusion Proteins (genetics), Recombinant Fusion Proteins (metabolism), Sirolimus (pharmacology).
MESH :
- chemical , adverse effects : Anti-Bacterial Agents, Azithromycin.
- chemical , genetics : Microtubule-Associated Proteins, Recombinant Fusion Proteins.
- chemical , metabolism : Microtubule-Associated Proteins, Recombinant Fusion Proteins.
- chemical , pharmacology : Anti-Bacterial Agents, Azithromycin, Enzyme Inhibitors, Macrolides, Sirolimus.
- chemical , therapeutic use : Anti-Bacterial Agents, Azithromycin.
- complications : Cystic Fibrosis.
- cytology : Macrophages.
- drug effects : Autophagy, Macrophages, Mycobacterium, Phagosomes.
- drug therapy : Cystic Fibrosis.
- etiology : Mycobacterium Infections.
- metabolism : Lysosomes, Phagosomes.
- microbiology : Cystic Fibrosis, Macrophages, Mycobacterium Infections.
- pathogenicity : Mycobacterium.
- physiology : Mycobacterium.
- Adult, Animals, COS Cells, Chlorocebus aethiops, Drug Resistance, Bacterial, HeLa Cells, Humans, Mice, Mice, Inbred C57BL.

Abstract

Azithromycin is a potent macrolide antibiotic with poorly understood antiinflammatory properties. Long-term use of azithromycin in patients with chronic inflammatory lung diseases, such as cystic fibrosis (CF), results in improved outcomes. Paradoxically, a recent study reported that azithromycin use in patients with CF is associated with increased infection with nontuberculous mycobacteria (NTM). Here, we confirm that long-term azithromycin use by adults with CF is associated with the development of infection with NTM, particularly the multi-drug-resistant species Mycobacterium abscessus, and identify an underlying mechanism. We found that in primary human macrophages, concentrations of azithromycin achieved during therapeutic dosing blocked autophagosome clearance by preventing lysosomal acidification, thereby impairing autophagic and phagosomal degradation. As a consequence, azithromycin treatment inhibited intracellular killing of mycobacteria within macrophages and resulted in chronic infection with NTM in mice. Our findings emphasize the essential role for autophagy in the host response to infection with NTM, reveal why chronic use of azithromycin may predispose to mycobacterial disease, and highlight the dangers of inadvertent pharmacological blockade of autophagy in patients at risk of infection with drug-resistant pathogens.

DOI: 10.1172/JCI46095
PubMed: 21804191
PubMed Central: PMC3163956

Affiliations:

Links toward previous steps (curation, corpus...)

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Le document en format XML

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<sourceDesc><biblStruct><analytic><title xml:lang="en">Azithromycin blocks autophagy and may predispose cystic fibrosis patients to mycobacterial infection.</title>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult (MeSH)</term>
<term>Animals (MeSH)</term>
<term>Anti-Bacterial Agents (adverse effects)</term>
<term>Anti-Bacterial Agents (pharmacology)</term>
<term>Anti-Bacterial Agents (therapeutic use)</term>
<term>Autophagy (drug effects)</term>
<term>Azithromycin (adverse effects)</term>
<term>Azithromycin (pharmacology)</term>
<term>Azithromycin (therapeutic use)</term>
<term>COS Cells (MeSH)</term>
<term>Chlorocebus aethiops (MeSH)</term>
<term>Cystic Fibrosis (complications)</term>
<term>Cystic Fibrosis (drug therapy)</term>
<term>Cystic Fibrosis (microbiology)</term>
<term>Drug Resistance, Bacterial (MeSH)</term>
<term>Enzyme Inhibitors (pharmacology)</term>
<term>HeLa Cells (MeSH)</term>
<term>Humans (MeSH)</term>
<term>Lysosomes (metabolism)</term>
<term>Macrolides (pharmacology)</term>
<term>Macrophages (cytology)</term>
<term>Macrophages (drug effects)</term>
<term>Macrophages (microbiology)</term>
<term>Mice (MeSH)</term>
<term>Mice, Inbred C57BL (MeSH)</term>
<term>Microtubule-Associated Proteins (genetics)</term>
<term>Microtubule-Associated Proteins (metabolism)</term>
<term>Mycobacterium (drug effects)</term>
<term>Mycobacterium (pathogenicity)</term>
<term>Mycobacterium (physiology)</term>
<term>Mycobacterium Infections (etiology)</term>
<term>Mycobacterium Infections (microbiology)</term>
<term>Phagosomes (drug effects)</term>
<term>Phagosomes (metabolism)</term>
<term>Recombinant Fusion Proteins (genetics)</term>
<term>Recombinant Fusion Proteins (metabolism)</term>
<term>Sirolimus (pharmacology)</term>
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<keywords scheme="KwdFr" xml:lang="fr"><term>Adulte (MeSH)</term>
<term>Animaux (MeSH)</term>
<term>Antibactériens (effets indésirables)</term>
<term>Antibactériens (pharmacologie)</term>
<term>Antibactériens (usage thérapeutique)</term>
<term>Antienzymes (pharmacologie)</term>
<term>Autophagie (effets des médicaments et des substances chimiques)</term>
<term>Azithromycine (effets indésirables)</term>
<term>Azithromycine (pharmacologie)</term>
<term>Azithromycine (usage thérapeutique)</term>
<term>Cellules COS (MeSH)</term>
<term>Cellules HeLa (MeSH)</term>
<term>Humains (MeSH)</term>
<term>Infections à Mycobacterium (microbiologie)</term>
<term>Infections à Mycobacterium (étiologie)</term>
<term>Lysosomes (métabolisme)</term>
<term>Macrolides (pharmacologie)</term>
<term>Macrophages (cytologie)</term>
<term>Macrophages (effets des médicaments et des substances chimiques)</term>
<term>Macrophages (microbiologie)</term>
<term>Mucoviscidose (complications)</term>
<term>Mucoviscidose (microbiologie)</term>
<term>Mucoviscidose (traitement médicamenteux)</term>
<term>Mycobacterium (effets des médicaments et des substances chimiques)</term>
<term>Mycobacterium (pathogénicité)</term>
<term>Mycobacterium (physiologie)</term>
<term>Phagosomes (effets des médicaments et des substances chimiques)</term>
<term>Phagosomes (métabolisme)</term>
<term>Protéines associées aux microtubules (génétique)</term>
<term>Protéines associées aux microtubules (métabolisme)</term>
<term>Protéines de fusion recombinantes (génétique)</term>
<term>Protéines de fusion recombinantes (métabolisme)</term>
<term>Résistance bactérienne aux médicaments (MeSH)</term>
<term>Sirolimus (pharmacologie)</term>
<term>Souris (MeSH)</term>
<term>Souris de lignée C57BL (MeSH)</term>
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<keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Anti-Bacterial Agents</term>
<term>Azithromycin</term>
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<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Microtubule-Associated Proteins</term>
<term>Recombinant Fusion Proteins</term>
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<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Microtubule-Associated Proteins</term>
<term>Recombinant Fusion Proteins</term>
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<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Anti-Bacterial Agents</term>
<term>Azithromycin</term>
<term>Enzyme Inhibitors</term>
<term>Macrolides</term>
<term>Sirolimus</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Anti-Bacterial Agents</term>
<term>Azithromycin</term>
</keywords>
<keywords scheme="MESH" qualifier="complications" xml:lang="en"><term>Cystic Fibrosis</term>
</keywords>
<keywords scheme="MESH" qualifier="cytologie" xml:lang="fr"><term>Macrophages</term>
</keywords>
<keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>Macrophages</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Autophagy</term>
<term>Macrophages</term>
<term>Mycobacterium</term>
<term>Phagosomes</term>
</keywords>
<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Cystic Fibrosis</term>
</keywords>
<keywords scheme="MESH" qualifier="effets des médicaments et des substances chimiques" xml:lang="fr"><term>Autophagie</term>
<term>Macrophages</term>
<term>Mycobacterium</term>
<term>Phagosomes</term>
</keywords>
<keywords scheme="MESH" qualifier="effets indésirables" xml:lang="fr"><term>Antibactériens</term>
<term>Azithromycine</term>
<term>Mucoviscidose</term>
</keywords>
<keywords scheme="MESH" qualifier="etiology" xml:lang="en"><term>Mycobacterium Infections</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Protéines associées aux microtubules</term>
<term>Protéines de fusion recombinantes</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Lysosomes</term>
<term>Phagosomes</term>
</keywords>
<keywords scheme="MESH" qualifier="microbiologie" xml:lang="fr"><term>Infections à Mycobacterium</term>
<term>Macrophages</term>
<term>Mucoviscidose</term>
</keywords>
<keywords scheme="MESH" qualifier="microbiology" xml:lang="en"><term>Cystic Fibrosis</term>
<term>Macrophages</term>
<term>Mycobacterium Infections</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Lysosomes</term>
<term>Phagosomes</term>
<term>Protéines associées aux microtubules</term>
<term>Protéines de fusion recombinantes</term>
</keywords>
<keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>Mycobacterium</term>
</keywords>
<keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr"><term>Mycobacterium</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Antibactériens</term>
<term>Antienzymes</term>
<term>Azithromycine</term>
<term>Macrolides</term>
<term>Sirolimus</term>
</keywords>
<keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Mycobacterium</term>
</keywords>
<keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Mycobacterium</term>
</keywords>
<keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Mucoviscidose</term>
</keywords>
<keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Antibactériens</term>
<term>Azithromycine</term>
</keywords>
<keywords scheme="MESH" qualifier="étiologie" xml:lang="fr"><term>Infections à Mycobacterium</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Adult</term>
<term>Animals</term>
<term>COS Cells</term>
<term>Chlorocebus aethiops</term>
<term>Drug Resistance, Bacterial</term>
<term>HeLa Cells</term>
<term>Humans</term>
<term>Mice</term>
<term>Mice, Inbred C57BL</term>
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<term>Animaux</term>
<term>Cellules COS</term>
<term>Cellules HeLa</term>
<term>Humains</term>
<term>Résistance bactérienne aux médicaments</term>
<term>Souris</term>
<term>Souris de lignée C57BL</term>
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<front><div type="abstract" xml:lang="en">Azithromycin is a potent macrolide antibiotic with poorly understood antiinflammatory properties. Long-term use of azithromycin in patients with chronic inflammatory lung diseases, such as cystic fibrosis (CF), results in improved outcomes. Paradoxically, a recent study reported that azithromycin use in patients with CF is associated with increased infection with nontuberculous mycobacteria (NTM). Here, we confirm that long-term azithromycin use by adults with CF is associated with the development of infection with NTM, particularly the multi-drug-resistant species Mycobacterium abscessus, and identify an underlying mechanism. We found that in primary human macrophages, concentrations of azithromycin achieved during therapeutic dosing blocked autophagosome clearance by preventing lysosomal acidification, thereby impairing autophagic and phagosomal degradation. As a consequence, azithromycin treatment inhibited intracellular killing of mycobacteria within macrophages and resulted in chronic infection with NTM in mice. Our findings emphasize the essential role for autophagy in the host response to infection with NTM, reveal why chronic use of azithromycin may predispose to mycobacterial disease, and highlight the dangers of inadvertent pharmacological blockade of autophagy in patients at risk of infection with drug-resistant pathogens.</div>
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<DateCompleted><Year>2011</Year>
<Month>10</Month>
<Day>31</Day>
</DateCompleted>
<DateRevised><Year>2019</Year>
<Month>12</Month>
<Day>10</Day>
</DateRevised>
<Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1558-8238</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>121</Volume>
<Issue>9</Issue>
<PubDate><Year>2011</Year>
<Month>Sep</Month>
</PubDate>
</JournalIssue>
<Title>The Journal of clinical investigation</Title>
<ISOAbbreviation>J Clin Invest</ISOAbbreviation>
</Journal>
<ArticleTitle>Azithromycin blocks autophagy and may predispose cystic fibrosis patients to mycobacterial infection.</ArticleTitle>
<Pagination><MedlinePgn>3554-63</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1172/JCI46095</ELocationID>
<ELocationID EIdType="pii" ValidYN="Y">46095</ELocationID>
<Abstract><AbstractText>Azithromycin is a potent macrolide antibiotic with poorly understood antiinflammatory properties. Long-term use of azithromycin in patients with chronic inflammatory lung diseases, such as cystic fibrosis (CF), results in improved outcomes. Paradoxically, a recent study reported that azithromycin use in patients with CF is associated with increased infection with nontuberculous mycobacteria (NTM). Here, we confirm that long-term azithromycin use by adults with CF is associated with the development of infection with NTM, particularly the multi-drug-resistant species Mycobacterium abscessus, and identify an underlying mechanism. We found that in primary human macrophages, concentrations of azithromycin achieved during therapeutic dosing blocked autophagosome clearance by preventing lysosomal acidification, thereby impairing autophagic and phagosomal degradation. As a consequence, azithromycin treatment inhibited intracellular killing of mycobacteria within macrophages and resulted in chronic infection with NTM in mice. Our findings emphasize the essential role for autophagy in the host response to infection with NTM, reveal why chronic use of azithromycin may predispose to mycobacterial disease, and highlight the dangers of inadvertent pharmacological blockade of autophagy in patients at risk of infection with drug-resistant pathogens.</AbstractText>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Renna</LastName>
<ForeName>Maurizio</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Schaffner</LastName>
<ForeName>Catherine</ForeName>
<Initials>C</Initials>
</Author>
<Author ValidYN="Y"><LastName>Brown</LastName>
<ForeName>Karen</ForeName>
<Initials>K</Initials>
</Author>
<Author ValidYN="Y"><LastName>Shang</LastName>
<ForeName>Shaobin</ForeName>
<Initials>S</Initials>
</Author>
<Author ValidYN="Y"><LastName>Tamayo</LastName>
<ForeName>Marcela Henao</ForeName>
<Initials>MH</Initials>
</Author>
<Author ValidYN="Y"><LastName>Hegyi</LastName>
<ForeName>Krisztina</ForeName>
<Initials>K</Initials>
</Author>
<Author ValidYN="Y"><LastName>Grimsey</LastName>
<ForeName>Neil J</ForeName>
<Initials>NJ</Initials>
</Author>
<Author ValidYN="Y"><LastName>Cusens</LastName>
<ForeName>David</ForeName>
<Initials>D</Initials>
</Author>
<Author ValidYN="Y"><LastName>Coulter</LastName>
<ForeName>Sarah</ForeName>
<Initials>S</Initials>
</Author>
<Author ValidYN="Y"><LastName>Cooper</LastName>
<ForeName>Jason</ForeName>
<Initials>J</Initials>
</Author>
<Author ValidYN="Y"><LastName>Bowden</LastName>
<ForeName>Anne R</ForeName>
<Initials>AR</Initials>
</Author>
<Author ValidYN="Y"><LastName>Newton</LastName>
<ForeName>Sandra M</ForeName>
<Initials>SM</Initials>
</Author>
<Author ValidYN="Y"><LastName>Kampmann</LastName>
<ForeName>Beate</ForeName>
<Initials>B</Initials>
</Author>
<Author ValidYN="Y"><LastName>Helm</LastName>
<ForeName>Jennifer</ForeName>
<Initials>J</Initials>
</Author>
<Author ValidYN="Y"><LastName>Jones</LastName>
<ForeName>Andrew</ForeName>
<Initials>A</Initials>
</Author>
<Author ValidYN="Y"><LastName>Haworth</LastName>
<ForeName>Charles S</ForeName>
<Initials>CS</Initials>
</Author>
<Author ValidYN="Y"><LastName>Basaraba</LastName>
<ForeName>Randall J</ForeName>
<Initials>RJ</Initials>
</Author>
<Author ValidYN="Y"><LastName>DeGroote</LastName>
<ForeName>Mary Ann</ForeName>
<Initials>MA</Initials>
</Author>
<Author ValidYN="Y"><LastName>Ordway</LastName>
<ForeName>Diane J</ForeName>
<Initials>DJ</Initials>
</Author>
<Author ValidYN="Y"><LastName>Rubinsztein</LastName>
<ForeName>David C</ForeName>
<Initials>DC</Initials>
</Author>
<Author ValidYN="Y"><LastName>Floto</LastName>
<ForeName>R Andres</ForeName>
<Initials>RA</Initials>
</Author>
</AuthorList>
<Language>eng</Language>
<GrantList CompleteYN="Y"><Grant><GrantID>MC_UP_A900_1122</GrantID>
<Agency>Medical Research Council</Agency>
<Country>United Kingdom</Country>
</Grant>
<Grant><Agency>Wellcome Trust</Agency>
<Country>United Kingdom</Country>
</Grant>
</GrantList>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
<PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2011</Year>
<Month>08</Month>
<Day>01</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>United States</Country>
<MedlineTA>J Clin Invest</MedlineTA>
<NlmUniqueID>7802877</NlmUniqueID>
<ISSNLinking>0021-9738</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList><Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D000900">Anti-Bacterial Agents</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D004791">Enzyme Inhibitors</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D018942">Macrolides</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D008869">Microtubule-Associated Proteins</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D011993">Recombinant Fusion Proteins</NameOfSubstance>
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<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="C466626">light chain 3, human</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>83905-01-5</RegistryNumber>
<NameOfSubstance UI="D017963">Azithromycin</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>88899-55-2</RegistryNumber>
<NameOfSubstance UI="C040929">bafilomycin A1</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>W36ZG6FT64</RegistryNumber>
<NameOfSubstance UI="D020123">Sirolimus</NameOfSubstance>
</Chemical>
</ChemicalList>
<CitationSubset>AIM</CitationSubset>
<CitationSubset>IM</CitationSubset>
<MeshHeadingList><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000900" MajorTopicYN="Y">Anti-Bacterial Agents</DescriptorName>
<QualifierName UI="Q000009" MajorTopicYN="N">adverse effects</QualifierName>
<QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName>
<QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D001343" MajorTopicYN="N">Autophagy</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D017963" MajorTopicYN="Y">Azithromycin</DescriptorName>
<QualifierName UI="Q000009" MajorTopicYN="N">adverse effects</QualifierName>
<QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName>
<QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D019556" MajorTopicYN="N">COS Cells</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D002522" MajorTopicYN="N">Chlorocebus aethiops</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D003550" MajorTopicYN="N">Cystic Fibrosis</DescriptorName>
<QualifierName UI="Q000150" MajorTopicYN="Y">complications</QualifierName>
<QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName>
<QualifierName UI="Q000382" MajorTopicYN="N">microbiology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D024881" MajorTopicYN="N">Drug Resistance, Bacterial</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D004791" MajorTopicYN="N">Enzyme Inhibitors</DescriptorName>
<QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006367" MajorTopicYN="N">HeLa Cells</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008247" MajorTopicYN="N">Lysosomes</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D018942" MajorTopicYN="N">Macrolides</DescriptorName>
<QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008264" MajorTopicYN="N">Macrophages</DescriptorName>
<QualifierName UI="Q000166" MajorTopicYN="N">cytology</QualifierName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
<QualifierName UI="Q000382" MajorTopicYN="N">microbiology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008810" MajorTopicYN="N">Mice, Inbred C57BL</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008869" MajorTopicYN="N">Microtubule-Associated Proteins</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D009161" MajorTopicYN="N">Mycobacterium</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
<QualifierName UI="Q000472" MajorTopicYN="N">pathogenicity</QualifierName>
<QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D009164" MajorTopicYN="N">Mycobacterium Infections</DescriptorName>
<QualifierName UI="Q000209" MajorTopicYN="Y">etiology</QualifierName>
<QualifierName UI="Q000382" MajorTopicYN="N">microbiology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D010588" MajorTopicYN="N">Phagosomes</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D011993" MajorTopicYN="N">Recombinant Fusion Proteins</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
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</MeshHeading>
<MeshHeading><DescriptorName UI="D020123" MajorTopicYN="N">Sirolimus</DescriptorName>
<QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName>
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<affiliations><list><country><li>Royaume-Uni</li>
</country>
<region><li>Angleterre</li>
<li>Angleterre de l'Est</li>
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</settlement>
<orgName><li>Université de Cambridge</li>
</orgName>
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<tree><noCountry><name sortKey="Basaraba, Randall J" sort="Basaraba, Randall J" uniqKey="Basaraba R" first="Randall J" last="Basaraba">Randall J. Basaraba</name>
<name sortKey="Bowden, Anne R" sort="Bowden, Anne R" uniqKey="Bowden A" first="Anne R" last="Bowden">Anne R. Bowden</name>
<name sortKey="Brown, Karen" sort="Brown, Karen" uniqKey="Brown K" first="Karen" last="Brown">Karen Brown</name>
<name sortKey="Cooper, Jason" sort="Cooper, Jason" uniqKey="Cooper J" first="Jason" last="Cooper">Jason Cooper</name>
<name sortKey="Coulter, Sarah" sort="Coulter, Sarah" uniqKey="Coulter S" first="Sarah" last="Coulter">Sarah Coulter</name>
<name sortKey="Cusens, David" sort="Cusens, David" uniqKey="Cusens D" first="David" last="Cusens">David Cusens</name>
<name sortKey="Degroote, Mary Ann" sort="Degroote, Mary Ann" uniqKey="Degroote M" first="Mary Ann" last="Degroote">Mary Ann Degroote</name>
<name sortKey="Floto, R Andres" sort="Floto, R Andres" uniqKey="Floto R" first="R Andres" last="Floto">R Andres Floto</name>
<name sortKey="Grimsey, Neil J" sort="Grimsey, Neil J" uniqKey="Grimsey N" first="Neil J" last="Grimsey">Neil J. Grimsey</name>
<name sortKey="Haworth, Charles S" sort="Haworth, Charles S" uniqKey="Haworth C" first="Charles S" last="Haworth">Charles S. Haworth</name>
<name sortKey="Hegyi, Krisztina" sort="Hegyi, Krisztina" uniqKey="Hegyi K" first="Krisztina" last="Hegyi">Krisztina Hegyi</name>
<name sortKey="Helm, Jennifer" sort="Helm, Jennifer" uniqKey="Helm J" first="Jennifer" last="Helm">Jennifer Helm</name>
<name sortKey="Jones, Andrew" sort="Jones, Andrew" uniqKey="Jones A" first="Andrew" last="Jones">Andrew Jones</name>
<name sortKey="Kampmann, Beate" sort="Kampmann, Beate" uniqKey="Kampmann B" first="Beate" last="Kampmann">Beate Kampmann</name>
<name sortKey="Newton, Sandra M" sort="Newton, Sandra M" uniqKey="Newton S" first="Sandra M" last="Newton">Sandra M. Newton</name>
<name sortKey="Ordway, Diane J" sort="Ordway, Diane J" uniqKey="Ordway D" first="Diane J" last="Ordway">Diane J. Ordway</name>
<name sortKey="Rubinsztein, David C" sort="Rubinsztein, David C" uniqKey="Rubinsztein D" first="David C" last="Rubinsztein">David C. Rubinsztein</name>
<name sortKey="Schaffner, Catherine" sort="Schaffner, Catherine" uniqKey="Schaffner C" first="Catherine" last="Schaffner">Catherine Schaffner</name>
<name sortKey="Shang, Shaobin" sort="Shang, Shaobin" uniqKey="Shang S" first="Shaobin" last="Shang">Shaobin Shang</name>
<name sortKey="Tamayo, Marcela Henao" sort="Tamayo, Marcela Henao" uniqKey="Tamayo M" first="Marcela Henao" last="Tamayo">Marcela Henao Tamayo</name>
</noCountry>
<country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Renna, Maurizio" sort="Renna, Maurizio" uniqKey="Renna M" first="Maurizio" last="Renna">Maurizio Renna</name>
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	Serveur d'exploration sur la rapamycine et les champignons
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Azithromycin blocks autophagy and may predispose cystic fibrosis patients to mycobacterial infection.

Azithromycin blocks autophagy and may predispose cystic fibrosis patients to mycobacterial infection.

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