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Microbial cell-free DNA in plasma of patients with sepsis: a potential diagnostic methodology.

Identifieur interne : 000020 ( Main/Exploration ); précédent : 000019; suivant : 000021

Microbial cell-free DNA in plasma of patients with sepsis: a potential diagnostic methodology.

Auteurs : Wei Liao [République populaire de Chine] ; Xiaoyu Zuo [République populaire de Chine] ; Guowang Lin [République populaire de Chine] ; Yaqing Zhou [République populaire de Chine] ; Yonghong Fu [République populaire de Chine] ; Shaohang Cai [République populaire de Chine] ; Pan-Pan Wei [République populaire de Chine] ; Yu-Xiang Liu [République populaire de Chine] ; Yang Liu [République populaire de Chine] ; Gang Ma [République populaire de Chine] ; Jin-Xin Bei [République populaire de Chine]

Source :

RBID : pubmed:33002409

Descripteurs français

English descriptors

Abstract

Sepsis is a life-threatening clinical condition demanding accurate and rapid diagnosis of the culprit pathogen, thereby to improve prognosis. Pathogen determination through blood culture is the gold standard for diagnosis but has limitations due to low sensitivity. Recently, circulating DNAs derived from pathogenic organisms were found in the plasma of patients with sepsis and were further proved to be more sensitive biomarkers for the diagnosis of the pathogen origin in sepsis. However, the fundamental molecular characteristics of circulating DNA in patients with sepsis remain unclear. Here, we used specific PCR and Sanger sequencing to verify the microbiology culture results via the corresponding plasma circulating DNA. We analyzed the composition and molecular characteristics of circulating DNA in septic patients using next-generation sequencing technology. We showed the presence of pathogen-derived circulating DNA in the plasma of patients with sepsis. The sizes of circulating DNA fragments derived from pathogenic bacteria showed a skewed unimodal distribution, while those derived from host cells showed a normal unimodal distribution. Lengths of fragments at peak concentration for both origins ranged from 150 bp to 200 bp, and reads mapping to pathogenic bacteria genome distributed uniformly on the reference. Our findings have improved our understanding of microbial circulating DNA in patients with sepsis as a potential methodology for the accurate diagnosis of sepsis, especially in light of an urgent need for such a diagnosis associated with the COVID-19 infection.

PubMed: 33002409


Affiliations:


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Le document en format XML

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<name sortKey="Liu, Yang" sort="Liu, Yang" uniqKey="Liu Y" first="Yang" last="Liu">Yang Liu</name>
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<name sortKey="Ma, Gang" sort="Ma, Gang" uniqKey="Ma G" first="Gang" last="Ma">Gang Ma</name>
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<nlm:affiliation>Corresponding author.</nlm:affiliation>
<wicri:noCountry code="no comma">Corresponding author.</wicri:noCountry>
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<name sortKey="Bei, Jin Xin" sort="Bei, Jin Xin" uniqKey="Bei J" first="Jin-Xin" last="Bei">Jin-Xin Bei</name>
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<term>Adult (MeSH)</term>
<term>Aged (MeSH)</term>
<term>Bacterial Infections (complications)</term>
<term>Bacterial Infections (diagnosis)</term>
<term>Bacterial Infections (microbiology)</term>
<term>Betacoronavirus (MeSH)</term>
<term>Cell-Free Nucleic Acids (analysis)</term>
<term>Cell-Free Nucleic Acids (blood)</term>
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<term>Coronavirus Infections (diagnosis)</term>
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<term>DNA, Bacterial (blood)</term>
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<term>Pandemics (MeSH)</term>
<term>Pneumonia, Viral (MeSH)</term>
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<term>Acides nucléiques acellulaires (sang)</term>
<term>Adulte (MeSH)</term>
<term>Adulte d'âge moyen (MeSH)</term>
<term>Analyse de séquence d'ADN (MeSH)</term>
<term>Betacoronavirus (MeSH)</term>
<term>Femelle (MeSH)</term>
<term>Humains (MeSH)</term>
<term>Infections bactériennes (complications)</term>
<term>Infections bactériennes (diagnostic)</term>
<term>Infections bactériennes (microbiologie)</term>
<term>Infections à coronavirus (diagnostic)</term>
<term>Mâle (MeSH)</term>
<term>Pandémies (MeSH)</term>
<term>Pneumopathie virale (MeSH)</term>
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<term>Sepsie (diagnostic)</term>
<term>Sepsie (microbiologie)</term>
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<term>Techniques de culture (MeSH)</term>
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<term>ADN bactérien</term>
<term>Acides nucléiques acellulaires</term>
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<term>Sepsie</term>
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<term>Aged</term>
<term>Betacoronavirus</term>
<term>Clinical Laboratory Techniques</term>
<term>Culture Techniques</term>
<term>Female</term>
<term>High-Throughput Nucleotide Sequencing</term>
<term>Humans</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Pandemics</term>
<term>Pneumonia, Viral</term>
<term>Polymerase Chain Reaction</term>
<term>Sequence Analysis, DNA</term>
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<term>Adulte d'âge moyen</term>
<term>Analyse de séquence d'ADN</term>
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<term>Femelle</term>
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<term>Mâle</term>
<term>Pandémies</term>
<term>Pneumopathie virale</term>
<term>Réaction de polymérisation en chaîne</term>
<term>Sujet âgé</term>
<term>Séquençage nucléotidique à haut débit</term>
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<div type="abstract" xml:lang="en">Sepsis is a life-threatening clinical condition demanding accurate and rapid diagnosis of the culprit pathogen, thereby to improve prognosis. Pathogen determination through blood culture is the gold standard for diagnosis but has limitations due to low sensitivity. Recently, circulating DNAs derived from pathogenic organisms were found in the plasma of patients with sepsis and were further proved to be more sensitive biomarkers for the diagnosis of the pathogen origin in sepsis. However, the fundamental molecular characteristics of circulating DNA in patients with sepsis remain unclear. Here, we used specific PCR and Sanger sequencing to verify the microbiology culture results via the corresponding plasma circulating DNA. We analyzed the composition and molecular characteristics of circulating DNA in septic patients using next-generation sequencing technology. We showed the presence of pathogen-derived circulating DNA in the plasma of patients with sepsis. The sizes of circulating DNA fragments derived from pathogenic bacteria showed a skewed unimodal distribution, while those derived from host cells showed a normal unimodal distribution. Lengths of fragments at peak concentration for both origins ranged from 150 bp to 200 bp, and reads mapping to pathogenic bacteria genome distributed uniformly on the reference. Our findings have improved our understanding of microbial circulating DNA in patients with sepsis as a potential methodology for the accurate diagnosis of sepsis, especially in light of an urgent need for such a diagnosis associated with the COVID-19 infection.</div>
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<PMID Version="1">33002409</PMID>
<DateCompleted>
<Year>2020</Year>
<Month>10</Month>
<Day>09</Day>
</DateCompleted>
<DateRevised>
<Year>2020</Year>
<Month>10</Month>
<Day>09</Day>
</DateRevised>
<Article PubModel="Print">
<Journal>
<ISSN IssnType="Electronic">1944-7930</ISSN>
<JournalIssue CitedMedium="Internet">
<Volume>29</Volume>
<Issue>157</Issue>
<PubDate>
<MedlineDate>2020 Mar-Apr</MedlineDate>
</PubDate>
</JournalIssue>
<Title>Discovery medicine</Title>
<ISOAbbreviation>Discov Med</ISOAbbreviation>
</Journal>
<ArticleTitle>Microbial cell-free DNA in plasma of patients with sepsis: a potential diagnostic methodology.</ArticleTitle>
<Pagination>
<MedlinePgn>129-137</MedlinePgn>
</Pagination>
<Abstract>
<AbstractText>Sepsis is a life-threatening clinical condition demanding accurate and rapid diagnosis of the culprit pathogen, thereby to improve prognosis. Pathogen determination through blood culture is the gold standard for diagnosis but has limitations due to low sensitivity. Recently, circulating DNAs derived from pathogenic organisms were found in the plasma of patients with sepsis and were further proved to be more sensitive biomarkers for the diagnosis of the pathogen origin in sepsis. However, the fundamental molecular characteristics of circulating DNA in patients with sepsis remain unclear. Here, we used specific PCR and Sanger sequencing to verify the microbiology culture results via the corresponding plasma circulating DNA. We analyzed the composition and molecular characteristics of circulating DNA in septic patients using next-generation sequencing technology. We showed the presence of pathogen-derived circulating DNA in the plasma of patients with sepsis. The sizes of circulating DNA fragments derived from pathogenic bacteria showed a skewed unimodal distribution, while those derived from host cells showed a normal unimodal distribution. Lengths of fragments at peak concentration for both origins ranged from 150 bp to 200 bp, and reads mapping to pathogenic bacteria genome distributed uniformly on the reference. Our findings have improved our understanding of microbial circulating DNA in patients with sepsis as a potential methodology for the accurate diagnosis of sepsis, especially in light of an urgent need for such a diagnosis associated with the COVID-19 infection.</AbstractText>
</Abstract>
<AuthorList CompleteYN="Y">
<Author ValidYN="Y" EqualContrib="Y">
<LastName>Liao</LastName>
<ForeName>Wei</ForeName>
<Initials>W</Initials>
<AffiliationInfo>
<Affiliation>Intensive Care Unit, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y" EqualContrib="Y">
<LastName>Zuo</LastName>
<ForeName>Xiaoyu</ForeName>
<Initials>X</Initials>
<AffiliationInfo>
<Affiliation>Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y" EqualContrib="Y">
<LastName>Lin</LastName>
<ForeName>Guowang</ForeName>
<Initials>G</Initials>
<AffiliationInfo>
<Affiliation>Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Zhou</LastName>
<ForeName>Yaqing</ForeName>
<Initials>Y</Initials>
<AffiliationInfo>
<Affiliation>Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Fu</LastName>
<ForeName>Yonghong</ForeName>
<Initials>Y</Initials>
<AffiliationInfo>
<Affiliation>Intensive Care Unit, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, 510641, Guangdong, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Cai</LastName>
<ForeName>Shaohang</ForeName>
<Initials>S</Initials>
<AffiliationInfo>
<Affiliation>Intensive Care Unit, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Wei</LastName>
<ForeName>Pan-Pan</ForeName>
<Initials>PP</Initials>
<AffiliationInfo>
<Affiliation>Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Liu</LastName>
<ForeName>Yu-Xiang</ForeName>
<Initials>YX</Initials>
<AffiliationInfo>
<Affiliation>Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Liu</LastName>
<ForeName>Yang</ForeName>
<Initials>Y</Initials>
<AffiliationInfo>
<Affiliation>Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Ma</LastName>
<ForeName>Gang</ForeName>
<Initials>G</Initials>
<AffiliationInfo>
<Affiliation>Intensive Care Unit, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, China.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Corresponding author.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Bei</LastName>
<ForeName>Jin-Xin</ForeName>
<Initials>JX</Initials>
<AffiliationInfo>
<Affiliation>Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, China.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Corresponding author.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<PublicationTypeList>
<PublicationType UI="D016428">Journal Article</PublicationType>
</PublicationTypeList>
</Article>
<MedlineJournalInfo>
<Country>United States</Country>
<MedlineTA>Discov Med</MedlineTA>
<NlmUniqueID>101250006</NlmUniqueID>
<ISSNLinking>1539-6509</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D000073888">Cell-Free Nucleic Acids</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D004269">DNA, Bacterial</NameOfSubstance>
</Chemical>
</ChemicalList>
<SupplMeshList>
<SupplMeshName Type="Disease" UI="C000657245">COVID-19</SupplMeshName>
<SupplMeshName Type="Protocol" UI="C000657964">COVID-19 diagnostic testing</SupplMeshName>
<SupplMeshName Type="Organism" UI="C000656484">severe acute respiratory syndrome coronavirus 2</SupplMeshName>
</SupplMeshList>
<CitationSubset>IM</CitationSubset>
<MeshHeadingList>
<MeshHeading>
<DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D000368" MajorTopicYN="N">Aged</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D001424" MajorTopicYN="N">Bacterial Infections</DescriptorName>
<QualifierName UI="Q000150" MajorTopicYN="N">complications</QualifierName>
<QualifierName UI="Q000175" MajorTopicYN="N">diagnosis</QualifierName>
<QualifierName UI="Q000382" MajorTopicYN="Y">microbiology</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D000073640" MajorTopicYN="N">Betacoronavirus</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D000073888" MajorTopicYN="N">Cell-Free Nucleic Acids</DescriptorName>
<QualifierName UI="Q000032" MajorTopicYN="N">analysis</QualifierName>
<QualifierName UI="Q000097" MajorTopicYN="Y">blood</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D019411" MajorTopicYN="N">Clinical Laboratory Techniques</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D018352" MajorTopicYN="N">Coronavirus Infections</DescriptorName>
<QualifierName UI="Q000175" MajorTopicYN="N">diagnosis</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D046508" MajorTopicYN="N">Culture Techniques</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D004269" MajorTopicYN="N">DNA, Bacterial</DescriptorName>
<QualifierName UI="Q000032" MajorTopicYN="N">analysis</QualifierName>
<QualifierName UI="Q000097" MajorTopicYN="Y">blood</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D059014" MajorTopicYN="N">High-Throughput Nucleotide Sequencing</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D009369" MajorTopicYN="N">Neoplasms</DescriptorName>
<QualifierName UI="Q000150" MajorTopicYN="N">complications</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D058873" MajorTopicYN="N">Pandemics</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D011024" MajorTopicYN="N">Pneumonia, Viral</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D016133" MajorTopicYN="N">Polymerase Chain Reaction</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D018805" MajorTopicYN="N">Sepsis</DescriptorName>
<QualifierName UI="Q000150" MajorTopicYN="N">complications</QualifierName>
<QualifierName UI="Q000175" MajorTopicYN="N">diagnosis</QualifierName>
<QualifierName UI="Q000382" MajorTopicYN="Y">microbiology</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D017422" MajorTopicYN="N">Sequence Analysis, DNA</DescriptorName>
</MeshHeading>
</MeshHeadingList>
</MedlineCitation>
<PubmedData>
<History>
<PubMedPubDate PubStatus="entrez">
<Year>2020</Year>
<Month>10</Month>
<Day>1</Day>
<Hour>20</Hour>
<Minute>10</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="pubmed">
<Year>2020</Year>
<Month>10</Month>
<Day>2</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="medline">
<Year>2020</Year>
<Month>10</Month>
<Day>10</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
</History>
<PublicationStatus>ppublish</PublicationStatus>
<ArticleIdList>
<ArticleId IdType="pubmed">33002409</ArticleId>
</ArticleIdList>
</PubmedData>
</pubmed>
<affiliations>
<list>
<country>
<li>République populaire de Chine</li>
</country>
</list>
<tree>
<country name="République populaire de Chine">
<noRegion>
<name sortKey="Liao, Wei" sort="Liao, Wei" uniqKey="Liao W" first="Wei" last="Liao">Wei Liao</name>
</noRegion>
<name sortKey="Bei, Jin Xin" sort="Bei, Jin Xin" uniqKey="Bei J" first="Jin-Xin" last="Bei">Jin-Xin Bei</name>
<name sortKey="Cai, Shaohang" sort="Cai, Shaohang" uniqKey="Cai S" first="Shaohang" last="Cai">Shaohang Cai</name>
<name sortKey="Fu, Yonghong" sort="Fu, Yonghong" uniqKey="Fu Y" first="Yonghong" last="Fu">Yonghong Fu</name>
<name sortKey="Lin, Guowang" sort="Lin, Guowang" uniqKey="Lin G" first="Guowang" last="Lin">Guowang Lin</name>
<name sortKey="Liu, Yang" sort="Liu, Yang" uniqKey="Liu Y" first="Yang" last="Liu">Yang Liu</name>
<name sortKey="Liu, Yu Xiang" sort="Liu, Yu Xiang" uniqKey="Liu Y" first="Yu-Xiang" last="Liu">Yu-Xiang Liu</name>
<name sortKey="Ma, Gang" sort="Ma, Gang" uniqKey="Ma G" first="Gang" last="Ma">Gang Ma</name>
<name sortKey="Wei, Pan Pan" sort="Wei, Pan Pan" uniqKey="Wei P" first="Pan-Pan" last="Wei">Pan-Pan Wei</name>
<name sortKey="Zhou, Yaqing" sort="Zhou, Yaqing" uniqKey="Zhou Y" first="Yaqing" last="Zhou">Yaqing Zhou</name>
<name sortKey="Zuo, Xiaoyu" sort="Zuo, Xiaoyu" uniqKey="Zuo X" first="Xiaoyu" last="Zuo">Xiaoyu Zuo</name>
</country>
</tree>
</affiliations>
</record>

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