Cost of surviving sepsis: a novel model of recovery from sepsis in Drosophila melanogaster.
Identifieur interne : 002114 ( PubMed/Checkpoint ); précédent : 002113; suivant : 002115Cost of surviving sepsis: a novel model of recovery from sepsis in Drosophila melanogaster.
Auteurs : Ata Murat Kaynar [États-Unis] ; Veli Bakalov [États-Unis] ; Silvia Martinez Laverde [États-Unis] ; Amélie I F. Cambriel [France] ; Byoung-Hoon Lee [Corée du Sud] ; Atif Towheed [États-Unis] ; Alyssa D. Gregory [États-Unis] ; Steven A R. Webb [Australie] ; Michael J. Palladino [États-Unis] ; Fernando A. Bozza [Brésil] ; Steven D. Shapiro [États-Unis] ; Derek C. Angus [États-Unis]Source :
- Intensive care medicine experimental [ 2197-425X ] ; 2016.
Abstract
Multiple organ failure, wasting, increased morbidity, and mortality following acute illness complicates the health span of patients surviving sepsis. Persistent inflammation has been implicated, and it is proposed that insulin signaling contributes to persistent inflammatory signaling during the recovery phase after sepsis. However, mechanisms are unknown and suitable pre-clinical models are lacking. We therefore developed a novel Drosophila melanogaster model of sepsis to recapitulate the clinical course of sepsis, explored inflammation over time, and its relation to impaired mobility, metabolic disturbance, and changes in lifespan.
DOI: 10.1186/s40635-016-0075-4
PubMed: 26791145
Affiliations:
- Australie, Brésil, Corée du Sud, France, États-Unis
- Pennsylvanie, Île-de-France
- Paris
- Université Paris-Descartes
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Cambriel</name><affiliation wicri:level="4"><nlm:affiliation>Université Paris Descartes, 75270, Paris, Cedex 06, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université Paris Descartes, 75270, Paris, Cedex 06</wicri:regionArea><wicri:noRegion>Cedex 06</wicri:noRegion><orgName type="university">Université Paris-Descartes</orgName><placeName><settlement type="city">Paris</settlement><region type="region" nuts="2">Île-de-France</region></placeName></affiliation></author><author><name sortKey="Lee, Byoung Hoon" sort="Lee, Byoung Hoon" uniqKey="Lee B" first="Byoung-Hoon" last="Lee">Byoung-Hoon Lee</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pulmonology and Allergy, Eulji University, Seoul, 139-711, Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Pulmonology and Allergy, Eulji University, Seoul, 139-711</wicri:regionArea><wicri:noRegion>139-711</wicri:noRegion></affiliation></author><author><name sortKey="Towheed, Atif" sort="Towheed, Atif" uniqKey="Towheed A" first="Atif" last="Towheed">Atif Towheed</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pharmacology and Chemical Biology, Pittsburgh, PA, 15260, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pharmacology and Chemical Biology, Pittsburgh, PA, 15260</wicri:regionArea><wicri:noRegion>15260</wicri:noRegion></affiliation></author><author><name sortKey="Gregory, Alyssa D" sort="Gregory, Alyssa D" uniqKey="Gregory A" first="Alyssa D" last="Gregory">Alyssa D. Gregory</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15261, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15261</wicri:regionArea><wicri:noRegion>15261</wicri:noRegion></affiliation></author><author><name sortKey="Webb, Steven A R" sort="Webb, Steven A R" uniqKey="Webb S" first="Steven A R" last="Webb">Steven A R. Webb</name><affiliation wicri:level="1"><nlm:affiliation>School of Population Health, University of Western Australia, Crawly, Perth, WA, 6009, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>School of Population Health, University of Western Australia, Crawly, Perth, WA, 6009</wicri:regionArea><wicri:noRegion>6009</wicri:noRegion></affiliation></author><author><name sortKey="Palladino, Michael J" sort="Palladino, Michael J" uniqKey="Palladino M" first="Michael J" last="Palladino">Michael J. Palladino</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pharmacology and Chemical Biology, Pittsburgh, PA, 15260, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pharmacology and Chemical Biology, Pittsburgh, PA, 15260</wicri:regionArea><wicri:noRegion>15260</wicri:noRegion></affiliation></author><author><name sortKey="Bozza, Fernando A" sort="Bozza, Fernando A" uniqKey="Bozza F" first="Fernando A" last="Bozza">Fernando A. Bozza</name><affiliation wicri:level="1"><nlm:affiliation>Instituto de Pesquisa Clínica Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, 21040-360, Brazil.</nlm:affiliation><country xml:lang="fr">Brésil</country><wicri:regionArea>Instituto de Pesquisa Clínica Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, 21040-360</wicri:regionArea><wicri:noRegion>21040-360</wicri:noRegion></affiliation></author><author><name sortKey="Shapiro, Steven D" sort="Shapiro, Steven D" uniqKey="Shapiro S" first="Steven D" last="Shapiro">Steven D. Shapiro</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15261, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15261</wicri:regionArea><wicri:noRegion>15261</wicri:noRegion></affiliation></author><author><name sortKey="Angus, Derek C" sort="Angus, Derek C" uniqKey="Angus D" first="Derek C" last="Angus">Derek C. Angus</name><affiliation wicri:level="2"><nlm:affiliation>Clinical Research, Investigation, and Systems Modeling of Acute Illness (CRISMA) Laboratory, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, 612 Scaife Hall, 3550 Terrace Street, Pittsburgh, 15261, PA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Clinical Research, Investigation, and Systems Modeling of Acute Illness (CRISMA) Laboratory, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, 612 Scaife Hall, 3550 Terrace Street, Pittsburgh, 15261, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author></analytic><series><title level="j">Intensive care medicine experimental</title><idno type="ISSN">2197-425X</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Multiple organ failure, wasting, increased morbidity, and mortality following acute illness complicates the health span of patients surviving sepsis. Persistent inflammation has been implicated, and it is proposed that insulin signaling contributes to persistent inflammatory signaling during the recovery phase after sepsis. However, mechanisms are unknown and suitable pre-clinical models are lacking. We therefore developed a novel Drosophila melanogaster model of sepsis to recapitulate the clinical course of sepsis, explored inflammation over time, and its relation to impaired mobility, metabolic disturbance, and changes in lifespan.</div></front></TEI><pubmed><MedlineCitation Status="PubMed-not-MEDLINE" Owner="NLM"><PMID Version="1">26791145</PMID><DateCreated><Year>2016</Year><Month>01</Month><Day>21</Day></DateCreated><DateCompleted><Year>2016</Year><Month>01</Month><Day>21</Day></DateCompleted><DateRevised><Year>2017</Year><Month>02</Month><Day>20</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Print">2197-425X</ISSN><JournalIssue CitedMedium="Print"><Volume>4</Volume><Issue>1</Issue><PubDate><Year>2016</Year><Month>Dec</Month></PubDate></JournalIssue><Title>Intensive care medicine experimental</Title><ISOAbbreviation>Intensive Care Med Exp</ISOAbbreviation></Journal><ArticleTitle>Cost of surviving sepsis: a novel model of recovery from sepsis in Drosophila melanogaster.</ArticleTitle><Pagination><MedlinePgn>4</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1186/s40635-016-0075-4</ELocationID><Abstract><AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">Multiple organ failure, wasting, increased morbidity, and mortality following acute illness complicates the health span of patients surviving sepsis. Persistent inflammation has been implicated, and it is proposed that insulin signaling contributes to persistent inflammatory signaling during the recovery phase after sepsis. However, mechanisms are unknown and suitable pre-clinical models are lacking. We therefore developed a novel Drosophila melanogaster model of sepsis to recapitulate the clinical course of sepsis, explored inflammation over time, and its relation to impaired mobility, metabolic disturbance, and changes in lifespan.</AbstractText><AbstractText Label="METHODS" NlmCategory="METHODS">We used wild-type (WT), Drosomycin-green fluorescent protein (GFP), and NF-κB-luc reporter male Drosophila melanogaster 4-5 days of age (unmanipulated). We infected Drosophila with Staphylococcus aureus (infected without treatment) or pricked with aseptic needles (sham). Subsets of insects were treated with oral linezolid after the infection (infected with antibiotics). We assessed rapid iterative negative geotaxis (RING) in all the groups as a surrogate for neuromuscular functional outcome up to 96 h following infection. We harvested the flies over the 7-day course to evaluate bacterial burden, inflammatory and metabolic pathway gene expression patterns, NF-κB translation, and metabolic reserve. We also followed the lifespan of the flies.</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">Our results showed that when treated with antibiotics, flies had improved survival compared to infected without treatment flies in the early phase of sepsis up to 1 week (81 %, p = 0.001). However, the lifespan of infected with antibiotics flies was significantly shorter than that of sham controls (p = 0.001). Among infected with antibiotic sepsis survivors, we observed persistent elevation of NF-κB in the absence of any obvious infection as shown by culturing flies surviving sepsis. In the same group, geotaxis had an early (18 h) and sustained decline compared to its baseline. Geotaxis in infected with antibiotics sepsis survivors was significantly lower than that in sham and age-matched unmanipulated flies at 18 and 48 h. Expression of antimicrobial peptides (AMP) remained significantly elevated over the course of 7 days after sepsis, especially drosomycin (5.7-fold, p = 0.0145) on day 7 compared to that of sham flies. Infected with antibiotics flies had a trend towards decreased Akt activation, yet their glucose stores were significantly lower than those of sham flies (p = 0.001). Sepsis survivors had increased lactate levels and LDH activity by 1 week, whereas ATP and pyruvate content was similar to that of the sham group.</AbstractText><AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">In summary, our model mimics human survivors of sepsis with persistent inflammation, impaired motility, dysregulated glucose metabolism, and shortened lifespan.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Kaynar</LastName><ForeName>Ata Murat</ForeName><Initials>AM</Initials><AffiliationInfo><Affiliation>Clinical Research, Investigation, and Systems Modeling of Acute Illness (CRISMA) Laboratory, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, 612 Scaife Hall, 3550 Terrace Street, Pittsburgh, 15261, PA, USA. kaynarm@upmc.edu.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bakalov</LastName><ForeName>Veli</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>Clinical Research, Investigation, and Systems Modeling of Acute Illness (CRISMA) Laboratory, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, 612 Scaife Hall, 3550 Terrace Street, Pittsburgh, 15261, PA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Laverde</LastName><ForeName>Silvia Martinez</ForeName><Initials>SM</Initials><AffiliationInfo><Affiliation>Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15261, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cambriel</LastName><ForeName>Amélie I F</ForeName><Initials>AI</Initials><AffiliationInfo><Affiliation>Université Paris Descartes, 75270, Paris, Cedex 06, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lee</LastName><ForeName>Byoung-Hoon</ForeName><Initials>BH</Initials><AffiliationInfo><Affiliation>Department of Pulmonology and Allergy, Eulji University, Seoul, 139-711, Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Towheed</LastName><ForeName>Atif</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Pharmacology and Chemical Biology, Pittsburgh, PA, 15260, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Present address: Center of Mitochondrial and Epigenomic Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gregory</LastName><ForeName>Alyssa D</ForeName><Initials>AD</Initials><AffiliationInfo><Affiliation>Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15261, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Webb</LastName><ForeName>Steven A R</ForeName><Initials>SA</Initials><AffiliationInfo><Affiliation>School of Population Health, University of Western Australia, Crawly, Perth, WA, 6009, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Palladino</LastName><ForeName>Michael J</ForeName><Initials>MJ</Initials><AffiliationInfo><Affiliation>Department of Pharmacology and Chemical Biology, Pittsburgh, PA, 15260, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bozza</LastName><ForeName>Fernando A</ForeName><Initials>FA</Initials><AffiliationInfo><Affiliation>Instituto de Pesquisa Clínica Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, 21040-360, Brazil.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Shapiro</LastName><ForeName>Steven D</ForeName><Initials>SD</Initials><AffiliationInfo><Affiliation>Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15261, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Angus</LastName><ForeName>Derek C</ForeName><Initials>DC</Initials><AffiliationInfo><Affiliation>Clinical Research, Investigation, and Systems Modeling of Acute Illness (CRISMA) Laboratory, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, 612 Scaife Hall, 3550 Terrace Street, Pittsburgh, 15261, PA, USA.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>R01 HL126711</GrantID><Acronym>HL</Acronym><Agency>NHLBI NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2016</Year><Month>01</Month><Day>21</Day></ArticleDate></Article><MedlineJournalInfo><Country>Germany</Country><MedlineTA>Intensive Care Med Exp</MedlineTA><NlmUniqueID>101645149</NlmUniqueID><ISSNLinking>2197-425X</ISSNLinking></MedlineJournalInfo><CommentsCorrectionsList><CommentsCorrections RefType="Cites"><RefSource>Crit Care. 2014 Sep 03;18(5):469</RefSource><PMID 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PubStatus="medline"><Year>2016</Year><Month>1</Month><Day>23</Day><Hour>6</Hour><Minute>1</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">26791145</ArticleId><ArticleId IdType="doi">10.1186/s40635-016-0075-4</ArticleId><ArticleId IdType="pii">10.1186/s40635-016-0075-4</ArticleId><ArticleId IdType="pmc">PMC4720623</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Australie</li><li>Brésil</li><li>Corée du Sud</li><li>France</li><li>États-Unis</li></country><region><li>Pennsylvanie</li><li>Île-de-France</li></region><settlement><li>Paris</li></settlement><orgName><li>Université Paris-Descartes</li></orgName></list><tree><country name="États-Unis"><region name="Pennsylvanie"><name sortKey="Kaynar, Ata Murat" sort="Kaynar, Ata Murat" uniqKey="Kaynar A" first="Ata Murat" last="Kaynar">Ata Murat Kaynar</name></region><name sortKey="Angus, Derek C" sort="Angus, Derek C" uniqKey="Angus D" first="Derek C" last="Angus">Derek C. Angus</name><name sortKey="Bakalov, Veli" sort="Bakalov, Veli" uniqKey="Bakalov V" first="Veli" last="Bakalov">Veli Bakalov</name><name sortKey="Gregory, Alyssa D" sort="Gregory, Alyssa D" uniqKey="Gregory A" first="Alyssa D" last="Gregory">Alyssa D. Gregory</name><name sortKey="Laverde, Silvia Martinez" sort="Laverde, Silvia Martinez" uniqKey="Laverde S" first="Silvia Martinez" last="Laverde">Silvia Martinez Laverde</name><name sortKey="Palladino, Michael J" sort="Palladino, Michael J" uniqKey="Palladino M" first="Michael J" last="Palladino">Michael J. Palladino</name><name sortKey="Shapiro, Steven D" sort="Shapiro, Steven D" uniqKey="Shapiro S" first="Steven D" last="Shapiro">Steven D. Shapiro</name><name sortKey="Towheed, Atif" sort="Towheed, Atif" uniqKey="Towheed A" first="Atif" last="Towheed">Atif Towheed</name></country><country name="France"><region name="Île-de-France"><name sortKey="Cambriel, Amelie I F" sort="Cambriel, Amelie I F" uniqKey="Cambriel A" first="Amélie I F" last="Cambriel">Amélie I F. Cambriel</name></region></country><country name="Corée du Sud"><noRegion><name sortKey="Lee, Byoung Hoon" sort="Lee, Byoung Hoon" uniqKey="Lee B" first="Byoung-Hoon" last="Lee">Byoung-Hoon Lee</name></noRegion></country><country name="Australie"><noRegion><name sortKey="Webb, Steven A R" sort="Webb, Steven A R" uniqKey="Webb S" first="Steven A R" last="Webb">Steven A R. Webb</name></noRegion></country><country name="Brésil"><noRegion><name sortKey="Bozza, Fernando A" sort="Bozza, Fernando A" uniqKey="Bozza F" first="Fernando A" last="Bozza">Fernando A. Bozza</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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