Hydroxychloroquine susceptibility determination of Coxiella burnetii in human embryonic lung (HEL) fibroblast cells.
Identifieur interne : 000163 ( PubMed/Corpus ); précédent : 000162; suivant : 000164Hydroxychloroquine susceptibility determination of Coxiella burnetii in human embryonic lung (HEL) fibroblast cells.
Auteurs : Emmanouil Angelakis ; Jacques Bou Khalil ; Marion Le Bideau ; Celine Perreal ; Bernard La Scola ; Didier RaoultSource :
- International journal of antimicrobial agents [ 1872-7913 ] ; 2017.
English descriptors
- KwdEn :
- MESH :
- chemical , pharmacology : Anti-Bacterial Agents, Doxycycline, Hydroxychloroquine.
- drug effects : Coxiella burnetii.
- microbiology : Fibroblasts.
- Adolescent, Adult, Aged, Aged, 80 and over, Cells, Cultured, Female, Humans, Male, Microbial Sensitivity Tests, Middle Aged.
Abstract
Coxiella burnetii, the causative agent of Q fever, survives and replicates in the acidic environment of monocytes/macrophages; hydroxychloroquine, through alkalinisation of the acidic vacuoles, is critical for the management of Q fever. In this study, a collection of C. burnetii strains isolated from human samples was tested to evaluate the in vitro minimum inhibitory concentrations (MICs) of doxycycline and hydroxychloroquine. Serial two-fold dilutions of doxycycline (0.25-8 mg/L) and hydroxychloroquine (0.25-4 mg/L) were added to C. burnetii-infected human embryonic lung (HEL) fibroblast cells after 48 h of incubation, in duplicate. DNA was detected by C. burnetii-specific semi-quantitative PCR with primers and probes designed for amplification of the IS1111 and IS30A spacers. A total of 29 C. burnetii isolates obtained from 29 patients were tested. Doxycycline MICs ranged from 0.25 mg/L to 0.5 mg/L and hydroxychloroquine MICs from 0.25 mg/L to >4 mg/L. Four C. burnetii stains had hydroxychloroquine MICs ≤ 1 mg/L. The concentration of hydroxychloroquine was associated with a significant decrease in C. burnetii DNA copies in HEL cells based on linear regression analysis (P= 0.01). Recommended serum concentrations of hydroxychloroquine significantly reduced the growth of C. burnetii. Moreover, some C. burnetii strains presented hydroxychloroquine MICs below the recommended serum concentrations, indicating that, for these cases, hydroxychloroquine treatment alone may even be effective.
DOI: 10.1016/j.ijantimicag.2017.02.015
PubMed: 28478211
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pubmed:28478211Le document en format XML
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Jean Moulin, 13385 Marseille, France.</nlm:affiliation></affiliation></author><author><name sortKey="Le Bideau, Marion" sort="Le Bideau, Marion" uniqKey="Le Bideau M" first="Marion" last="Le Bideau">Marion Le Bideau</name><affiliation><nlm:affiliation>Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Faculté de Médecine, Aix-Marseille Université, CNRS-IRD 198 UMR 6236, 27 Bd. Jean Moulin, 13385 Marseille, France.</nlm:affiliation></affiliation></author><author><name sortKey="Perreal, Celine" sort="Perreal, Celine" uniqKey="Perreal C" first="Celine" last="Perreal">Celine Perreal</name><affiliation><nlm:affiliation>Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Faculté de Médecine, Aix-Marseille Université, CNRS-IRD 198 UMR 6236, 27 Bd. 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Jean Moulin, 13385 Marseille, France.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2017">2017</date><idno type="RBID">pubmed:28478211</idno><idno type="pmid">28478211</idno><idno type="doi">10.1016/j.ijantimicag.2017.02.015</idno><idno type="wicri:Area/PubMed/Corpus">000163</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000163</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Hydroxychloroquine susceptibility determination of Coxiella burnetii in human embryonic lung (HEL) fibroblast cells.</title><author><name sortKey="Angelakis, Emmanouil" sort="Angelakis, Emmanouil" uniqKey="Angelakis E" first="Emmanouil" last="Angelakis">Emmanouil Angelakis</name><affiliation><nlm:affiliation>Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Faculté de Médecine, Aix-Marseille Université, CNRS-IRD 198 UMR 6236, 27 Bd. Jean Moulin, 13385 Marseille, France. Electronic address: angelotasmanos@msn.com.</nlm:affiliation></affiliation></author><author><name sortKey="Khalil, Jacques Bou" sort="Khalil, Jacques Bou" uniqKey="Khalil J" first="Jacques Bou" last="Khalil">Jacques Bou Khalil</name><affiliation><nlm:affiliation>Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Faculté de Médecine, Aix-Marseille Université, CNRS-IRD 198 UMR 6236, 27 Bd. Jean Moulin, 13385 Marseille, France.</nlm:affiliation></affiliation></author><author><name sortKey="Le Bideau, Marion" sort="Le Bideau, Marion" uniqKey="Le Bideau M" first="Marion" last="Le Bideau">Marion Le Bideau</name><affiliation><nlm:affiliation>Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Faculté de Médecine, Aix-Marseille Université, CNRS-IRD 198 UMR 6236, 27 Bd. Jean Moulin, 13385 Marseille, France.</nlm:affiliation></affiliation></author><author><name sortKey="Perreal, Celine" sort="Perreal, Celine" uniqKey="Perreal C" first="Celine" last="Perreal">Celine Perreal</name><affiliation><nlm:affiliation>Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Faculté de Médecine, Aix-Marseille Université, CNRS-IRD 198 UMR 6236, 27 Bd. Jean Moulin, 13385 Marseille, France.</nlm:affiliation></affiliation></author><author><name sortKey="La Scola, Bernard" sort="La Scola, Bernard" uniqKey="La Scola B" first="Bernard" last="La Scola">Bernard La Scola</name><affiliation><nlm:affiliation>Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Faculté de Médecine, Aix-Marseille Université, CNRS-IRD 198 UMR 6236, 27 Bd. Jean Moulin, 13385 Marseille, France.</nlm:affiliation></affiliation></author><author><name sortKey="Raoult, Didier" sort="Raoult, Didier" uniqKey="Raoult D" first="Didier" last="Raoult">Didier Raoult</name><affiliation><nlm:affiliation>Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Faculté de Médecine, Aix-Marseille Université, CNRS-IRD 198 UMR 6236, 27 Bd. Jean Moulin, 13385 Marseille, France.</nlm:affiliation></affiliation></author></analytic><series><title level="j">International journal of antimicrobial agents</title><idno type="eISSN">1872-7913</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adolescent</term><term>Adult</term><term>Aged</term><term>Aged, 80 and over</term><term>Anti-Bacterial Agents (pharmacology)</term><term>Cells, Cultured</term><term>Coxiella burnetii (drug effects)</term><term>Doxycycline (pharmacology)</term><term>Female</term><term>Fibroblasts (microbiology)</term><term>Humans</term><term>Hydroxychloroquine (pharmacology)</term><term>Male</term><term>Microbial Sensitivity Tests</term><term>Middle Aged</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Anti-Bacterial Agents</term><term>Doxycycline</term><term>Hydroxychloroquine</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Coxiella burnetii</term></keywords><keywords scheme="MESH" qualifier="microbiology" xml:lang="en"><term>Fibroblasts</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adolescent</term><term>Adult</term><term>Aged</term><term>Aged, 80 and over</term><term>Cells, Cultured</term><term>Female</term><term>Humans</term><term>Male</term><term>Microbial Sensitivity Tests</term><term>Middle Aged</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Coxiella burnetii, the causative agent of Q fever, survives and replicates in the acidic environment of monocytes/macrophages; hydroxychloroquine, through alkalinisation of the acidic vacuoles, is critical for the management of Q fever. In this study, a collection of C. burnetii strains isolated from human samples was tested to evaluate the in vitro minimum inhibitory concentrations (MICs) of doxycycline and hydroxychloroquine. Serial two-fold dilutions of doxycycline (0.25-8 mg/L) and hydroxychloroquine (0.25-4 mg/L) were added to C. burnetii-infected human embryonic lung (HEL) fibroblast cells after 48 h of incubation, in duplicate. DNA was detected by C. burnetii-specific semi-quantitative PCR with primers and probes designed for amplification of the IS1111 and IS30A spacers. A total of 29 C. burnetii isolates obtained from 29 patients were tested. Doxycycline MICs ranged from 0.25 mg/L to 0.5 mg/L and hydroxychloroquine MICs from 0.25 mg/L to >4 mg/L. Four C. burnetii stains had hydroxychloroquine MICs ≤ 1 mg/L. The concentration of hydroxychloroquine was associated with a significant decrease in C. burnetii DNA copies in HEL cells based on linear regression analysis (P= 0.01). Recommended serum concentrations of hydroxychloroquine significantly reduced the growth of C. burnetii. Moreover, some C. burnetii strains presented hydroxychloroquine MICs below the recommended serum concentrations, indicating that, for these cases, hydroxychloroquine treatment alone may even be effective.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">28478211</PMID><DateCompleted><Year>2018</Year><Month>02</Month><Day>22</Day></DateCompleted><DateRevised><Year>2018</Year><Month>02</Month><Day>22</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1872-7913</ISSN><JournalIssue CitedMedium="Internet"><Volume>50</Volume><Issue>1</Issue><PubDate><Year>2017</Year><Month>Jul</Month></PubDate></JournalIssue><Title>International journal of antimicrobial agents</Title><ISOAbbreviation>Int. J. Antimicrob. Agents</ISOAbbreviation></Journal><ArticleTitle>Hydroxychloroquine susceptibility determination of Coxiella burnetii in human embryonic lung (HEL) fibroblast cells.</ArticleTitle><Pagination><MedlinePgn>106-109</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">S0924-8579(17)30140-1</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.ijantimicag.2017.02.015</ELocationID><Abstract><AbstractText>Coxiella burnetii, the causative agent of Q fever, survives and replicates in the acidic environment of monocytes/macrophages; hydroxychloroquine, through alkalinisation of the acidic vacuoles, is critical for the management of Q fever. In this study, a collection of C. burnetii strains isolated from human samples was tested to evaluate the in vitro minimum inhibitory concentrations (MICs) of doxycycline and hydroxychloroquine. Serial two-fold dilutions of doxycycline (0.25-8 mg/L) and hydroxychloroquine (0.25-4 mg/L) were added to C. burnetii-infected human embryonic lung (HEL) fibroblast cells after 48 h of incubation, in duplicate. DNA was detected by C. burnetii-specific semi-quantitative PCR with primers and probes designed for amplification of the IS1111 and IS30A spacers. A total of 29 C. burnetii isolates obtained from 29 patients were tested. Doxycycline MICs ranged from 0.25 mg/L to 0.5 mg/L and hydroxychloroquine MICs from 0.25 mg/L to >4 mg/L. Four C. burnetii stains had hydroxychloroquine MICs ≤ 1 mg/L. The concentration of hydroxychloroquine was associated with a significant decrease in C. burnetii DNA copies in HEL cells based on linear regression analysis (P= 0.01). Recommended serum concentrations of hydroxychloroquine significantly reduced the growth of C. burnetii. Moreover, some C. burnetii strains presented hydroxychloroquine MICs below the recommended serum concentrations, indicating that, for these cases, hydroxychloroquine treatment alone may even be effective.</AbstractText><CopyrightInformation>Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Angelakis</LastName><ForeName>Emmanouil</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Faculté de Médecine, Aix-Marseille Université, CNRS-IRD 198 UMR 6236, 27 Bd. Jean Moulin, 13385 Marseille, France. Electronic address: angelotasmanos@msn.com.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Khalil</LastName><ForeName>Jacques Bou</ForeName><Initials>JB</Initials><AffiliationInfo><Affiliation>Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Faculté de Médecine, Aix-Marseille Université, CNRS-IRD 198 UMR 6236, 27 Bd. Jean Moulin, 13385 Marseille, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Le Bideau</LastName><ForeName>Marion</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Faculté de Médecine, Aix-Marseille Université, CNRS-IRD 198 UMR 6236, 27 Bd. Jean Moulin, 13385 Marseille, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Perreal</LastName><ForeName>Celine</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Faculté de Médecine, Aix-Marseille Université, CNRS-IRD 198 UMR 6236, 27 Bd. Jean Moulin, 13385 Marseille, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>La Scola</LastName><ForeName>Bernard</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Faculté de Médecine, Aix-Marseille Université, CNRS-IRD 198 UMR 6236, 27 Bd. Jean Moulin, 13385 Marseille, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Raoult</LastName><ForeName>Didier</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Faculté de Médecine, Aix-Marseille Université, CNRS-IRD 198 UMR 6236, 27 Bd. Jean Moulin, 13385 Marseille, France.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2017</Year><Month>05</Month><Day>03</Day></ArticleDate></Article><MedlineJournalInfo><Country>Netherlands</Country><MedlineTA>Int J Antimicrob Agents</MedlineTA><NlmUniqueID>9111860</NlmUniqueID><ISSNLinking>0924-8579</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000900">Anti-Bacterial Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>4QWG6N8QKH</RegistryNumber><NameOfSubstance UI="D006886">Hydroxychloroquine</NameOfSubstance></Chemical><Chemical><RegistryNumber>N12000U13O</RegistryNumber><NameOfSubstance UI="D004318">Doxycycline</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000293" MajorTopicYN="N">Adolescent</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000368" MajorTopicYN="N">Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000369" MajorTopicYN="N">Aged, 80 and over</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000900" MajorTopicYN="N">Anti-Bacterial Agents</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002478" MajorTopicYN="N">Cells, Cultured</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016997" MajorTopicYN="N">Coxiella burnetii</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004318" MajorTopicYN="N">Doxycycline</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005347" MajorTopicYN="N">Fibroblasts</DescriptorName><QualifierName UI="Q000382" MajorTopicYN="Y">microbiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006886" MajorTopicYN="N">Hydroxychloroquine</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008826" MajorTopicYN="N">Microbial Sensitivity Tests</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Coxiella burnetii</Keyword><Keyword MajorTopicYN="N">Doxycycline</Keyword><Keyword MajorTopicYN="N">Hydroxychloroquine</Keyword><Keyword MajorTopicYN="N">MIC</Keyword><Keyword MajorTopicYN="N">Minimum inhibitory concentration</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2017</Year><Month>01</Month><Day>03</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2017</Year><Month>02</Month><Day>13</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2017</Year><Month>02</Month><Day>15</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2017</Year><Month>5</Month><Day>10</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2018</Year><Month>2</Month><Day>23</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2017</Year><Month>5</Month><Day>8</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">28478211</ArticleId><ArticleId IdType="pii">S0924-8579(17)30140-1</ArticleId><ArticleId IdType="doi">10.1016/j.ijantimicag.2017.02.015</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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