Genome-wide association studies of Shigella spp. and Enteroinvasive Escherichia coli isolates demonstrate an absence of genetic markers for prediction of disease severity
Identifieur interne : 000307 ( Pmc/Curation ); précédent : 000306; suivant : 000308Genome-wide association studies of Shigella spp. and Enteroinvasive Escherichia coli isolates demonstrate an absence of genetic markers for prediction of disease severity
Auteurs : Amber C. A. Hendriks [Pays-Bas] ; Frans A. G. Reubsaet [Pays-Bas] ; A. M. D. Mirjam Kooistra-Smid [Pays-Bas] ; John W. A. Rossen [Pays-Bas] ; Bas E. Dutilh [Pays-Bas] ; Aldert L. Zomer [Pays-Bas] ; Maaike J. C. Van Den Beld [Pays-Bas]Source :
- BMC Genomics [ 1471-2164 ] ; 2020.
Abstract
We investigated the association of symptoms and disease severity of shigellosis patients with genetic determinants of infecting
The isolates obtained were representative of the population structure encountered in other Western European countries. No association was found between single genes or combinations of genes and separate symptoms or disease severity scores. Our benchmark characteristic, genus, resulted in eight associated genes and > 3,000,000 k-mers, indicating adequate performance of the algorithms used.
To conclude, using several microbial GWAS methods, genetic variants in
Url:
DOI: 10.1186/s12864-020-6555-7
PubMed: 32041522
PubMed Central: 7011524
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Genome-wide association studies of <italic>Shigella spp.</italic> and Enteroinvasive <italic>Escherichia coli</italic> isolates demonstrate an absence of genetic markers for prediction of disease severity</title><author><name sortKey="Hendriks, Amber C A" sort="Hendriks, Amber C A" uniqKey="Hendriks A" first="Amber C. A." last="Hendriks">Amber C. A. 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Mirjam Kooistra-Smid</name><affiliation wicri:level="1"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.491139.7</institution-id><institution>Department of Medical Microbiology, Certe,</institution></institution-wrap>Groningen, the Netherlands</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Groningen</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9558 4598</institution-id><institution-id institution-id-type="GRID">grid.4494.d</institution-id><institution>Department of Medical Microbiology and Infection Prevention,</institution><institution>University of Groningen, University Medical Center Groningen,</institution></institution-wrap>Groningen, the Netherlands</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Groningen</wicri:regionArea></affiliation></author><author><name sortKey="Rossen, John W A" sort="Rossen, John W A" uniqKey="Rossen J" first="John W. 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Dutilh</name><affiliation wicri:level="1"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="ISNI">0000000120346234</institution-id><institution-id institution-id-type="GRID">grid.5477.1</institution-id><institution>Theoretical Biology and Bioinformatics, Science for Life,</institution><institution>Utrecht University,</institution></institution-wrap>Utrecht, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Utrecht</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0444 9382</institution-id><institution-id institution-id-type="GRID">grid.10417.33</institution-id><institution>Centre for Molecular and Biomolecular Informatics,</institution><institution>Radboud University Medical Centre,</institution></institution-wrap>Nijmegen, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Nijmegen</wicri:regionArea></affiliation></author><author><name sortKey="Zomer, Aldert L" sort="Zomer, Aldert L" uniqKey="Zomer A" first="Aldert L." last="Zomer">Aldert L. 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Van Den Beld</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2208 0118</institution-id><institution-id institution-id-type="GRID">grid.31147.30</institution-id><institution>Infectious Disease Research, Diagnostics and laboratory Surveillance, Centre for Infectious Disease Control,</institution><institution>National Institute for Public Health and the Environment,</institution></institution-wrap>Bilthoven, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Bilthoven</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9558 4598</institution-id><institution-id institution-id-type="GRID">grid.4494.d</institution-id><institution>Department of Medical Microbiology and Infection Prevention,</institution><institution>University of Groningen, University Medical Center Groningen,</institution></institution-wrap>Groningen, the Netherlands</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Groningen</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">32041522</idno><idno type="pmc">7011524</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7011524</idno><idno type="RBID">PMC:7011524</idno><idno type="doi">10.1186/s12864-020-6555-7</idno><date when="2020">2020</date><idno type="wicri:Area/Pmc/Corpus">000307</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000307</idno><idno type="wicri:Area/Pmc/Curation">000307</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000307</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Genome-wide association studies of <italic>Shigella spp.</italic> and Enteroinvasive <italic>Escherichia coli</italic> isolates demonstrate an absence of genetic markers for prediction of disease severity</title><author><name sortKey="Hendriks, Amber C A" sort="Hendriks, Amber C A" uniqKey="Hendriks A" first="Amber C. A." last="Hendriks">Amber C. A. Hendriks</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2208 0118</institution-id><institution-id institution-id-type="GRID">grid.31147.30</institution-id><institution>Infectious Disease Research, Diagnostics and laboratory Surveillance, Centre for Infectious Disease Control,</institution><institution>National Institute for Public Health and the Environment,</institution></institution-wrap>Bilthoven, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Bilthoven</wicri:regionArea></affiliation></author><author><name sortKey="Reubsaet, Frans A G" sort="Reubsaet, Frans A G" uniqKey="Reubsaet F" first="Frans A. G." last="Reubsaet">Frans A. G. Reubsaet</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2208 0118</institution-id><institution-id institution-id-type="GRID">grid.31147.30</institution-id><institution>Infectious Disease Research, Diagnostics and laboratory Surveillance, Centre for Infectious Disease Control,</institution><institution>National Institute for Public Health and the Environment,</institution></institution-wrap>Bilthoven, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Bilthoven</wicri:regionArea></affiliation></author><author><name sortKey="Kooistra Smid, A M D Mirjam" sort="Kooistra Smid, A M D Mirjam" uniqKey="Kooistra Smid A" first="A. M. D. Mirjam" last="Kooistra-Smid">A. M. D. Mirjam Kooistra-Smid</name><affiliation wicri:level="1"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.491139.7</institution-id><institution>Department of Medical Microbiology, Certe,</institution></institution-wrap>Groningen, the Netherlands</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Groningen</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9558 4598</institution-id><institution-id institution-id-type="GRID">grid.4494.d</institution-id><institution>Department of Medical Microbiology and Infection Prevention,</institution><institution>University of Groningen, University Medical Center Groningen,</institution></institution-wrap>Groningen, the Netherlands</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Groningen</wicri:regionArea></affiliation></author><author><name sortKey="Rossen, John W A" sort="Rossen, John W A" uniqKey="Rossen J" first="John W. A." last="Rossen">John W. A. Rossen</name><affiliation wicri:level="1"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9558 4598</institution-id><institution-id institution-id-type="GRID">grid.4494.d</institution-id><institution>Department of Medical Microbiology and Infection Prevention,</institution><institution>University of Groningen, University Medical Center Groningen,</institution></institution-wrap>Groningen, the Netherlands</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Groningen</wicri:regionArea></affiliation></author><author><name sortKey="Dutilh, Bas E" sort="Dutilh, Bas E" uniqKey="Dutilh B" first="Bas E." last="Dutilh">Bas E. Dutilh</name><affiliation wicri:level="1"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="ISNI">0000000120346234</institution-id><institution-id institution-id-type="GRID">grid.5477.1</institution-id><institution>Theoretical Biology and Bioinformatics, Science for Life,</institution><institution>Utrecht University,</institution></institution-wrap>Utrecht, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Utrecht</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0444 9382</institution-id><institution-id institution-id-type="GRID">grid.10417.33</institution-id><institution>Centre for Molecular and Biomolecular Informatics,</institution><institution>Radboud University Medical Centre,</institution></institution-wrap>Nijmegen, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Nijmegen</wicri:regionArea></affiliation></author><author><name sortKey="Zomer, Aldert L" sort="Zomer, Aldert L" uniqKey="Zomer A" first="Aldert L." last="Zomer">Aldert L. Zomer</name><affiliation wicri:level="1"><nlm:aff id="Aff6"><institution-wrap><institution-id institution-id-type="ISNI">0000000120346234</institution-id><institution-id institution-id-type="GRID">grid.5477.1</institution-id><institution>Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine,</institution><institution>Utrecht University,</institution></institution-wrap>Utrecht, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Utrecht</wicri:regionArea></affiliation></author><author><name sortKey="Van Den Beld, Maaike J C" sort="Van Den Beld, Maaike J C" uniqKey="Van Den Beld M" first="Maaike J. C." last="Van Den Beld">Maaike J. C. Van Den Beld</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2208 0118</institution-id><institution-id institution-id-type="GRID">grid.31147.30</institution-id><institution>Infectious Disease Research, Diagnostics and laboratory Surveillance, Centre for Infectious Disease Control,</institution><institution>National Institute for Public Health and the Environment,</institution></institution-wrap>Bilthoven, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Bilthoven</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9558 4598</institution-id><institution-id institution-id-type="GRID">grid.4494.d</institution-id><institution>Department of Medical Microbiology and Infection Prevention,</institution><institution>University of Groningen, University Medical Center Groningen,</institution></institution-wrap>Groningen, the Netherlands</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Groningen</wicri:regionArea></affiliation></author></analytic><series><title level="j">BMC Genomics</title><idno type="eISSN">1471-2164</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p id="Par1">We investigated the association of symptoms and disease severity of shigellosis patients with genetic determinants of infecting <italic>Shigella</italic> and entero-invasive <italic>Escherichia coli</italic> (EIEC), because determinants that predict disease outcome per individual patient could be used to prioritize control measures. For this purpose, genome wide association studies (GWAS) were performed using presence or absence of single genes, combinations of genes, and k-mers. All genetic variants were derived from draft genome sequences of isolates from a multicenter cross-sectional study conducted in the Netherlands during 2016 and 2017. Clinical data of patients consisting of binary/dichotomous representation of symptoms and their calculated severity scores were also available from this study. To verify the suitability of the methods used, the genetic differences between the genera <italic>Shigella</italic> and <italic>Escherichia</italic> were used as control.</p></sec><sec><title>Results</title><p id="Par2">The isolates obtained were representative of the population structure encountered in other Western European countries. No association was found between single genes or combinations of genes and separate symptoms or disease severity scores. Our benchmark characteristic, genus, resulted in eight associated genes and > 3,000,000 k-mers, indicating adequate performance of the algorithms used.</p></sec><sec><title>Conclusions</title><p id="Par3">To conclude, using several microbial GWAS methods, genetic variants in <italic>Shigella spp.</italic> and EIEC that can predict specific symptoms or a more severe course of disease were not identified, suggesting that disease severity of shigellosis is dependent on other factors than the genetic variation of the infecting bacteria. Specific genes or gene fragments of isolates from patients are unsuitable to predict outcomes and cannot be used for development, prioritization and optimization of guidelines for control measures of shigellosis or infections with EIEC.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Hale, Tl" uniqKey="Hale T">TL Hale</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lan, R" uniqKey="Lan R">R Lan</name></author><author><name sortKey="Reeves, Pr" uniqKey="Reeves P">PR Reeves</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pettengill, Ea" uniqKey="Pettengill E">EA Pettengill</name></author><author><name sortKey="Pettengill, Jb" uniqKey="Pettengill J">JB Pettengill</name></author><author><name sortKey="Binet, R" uniqKey="Binet R">R Binet</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Levine, Mm" 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A.</given-names></name></contrib><contrib contrib-type="author"><name><surname>van Dam</surname><given-names>A. P.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Svraka-Latifovic</surname><given-names>S.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Verweij</surname><given-names>J. J.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Bruijnesteijn van Coppenraet</surname><given-names>L. E. S.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Waar</surname><given-names>K.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Hermans</surname><given-names>M.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Hess</surname><given-names>D. L. J.</given-names></name></contrib><contrib contrib-type="author"><name><surname>van Mook</surname><given-names>L. J. M.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Bergmans</surname><given-names>M. C.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Jansen</surname><given-names>R. R.</given-names></name></contrib><contrib contrib-type="author"><name><surname>van de Bovenkamp</surname><given-names>J. H. B.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Demeulemeester</surname><given-names>A.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Reinders</surname><given-names>E.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Linssen</surname><given-names>C. F. M.</given-names></name></contrib></contrib-group></collab></contrib><aff id="Aff1"><label>1</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2208 0118</institution-id><institution-id institution-id-type="GRID">grid.31147.30</institution-id><institution>Infectious Disease Research, Diagnostics and laboratory Surveillance, Centre for Infectious Disease Control,</institution><institution>National Institute for Public Health and the Environment,</institution></institution-wrap>Bilthoven, The Netherlands</aff><aff id="Aff2"><label>2</label><institution-wrap><institution-id institution-id-type="GRID">grid.491139.7</institution-id><institution>Department of Medical Microbiology, Certe,</institution></institution-wrap>Groningen, the Netherlands</aff><aff id="Aff3"><label>3</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9558 4598</institution-id><institution-id institution-id-type="GRID">grid.4494.d</institution-id><institution>Department of Medical Microbiology and Infection Prevention,</institution><institution>University of Groningen, University Medical Center Groningen,</institution></institution-wrap>Groningen, the Netherlands</aff><aff id="Aff4"><label>4</label><institution-wrap><institution-id institution-id-type="ISNI">0000000120346234</institution-id><institution-id institution-id-type="GRID">grid.5477.1</institution-id><institution>Theoretical Biology and Bioinformatics, Science for Life,</institution><institution>Utrecht University,</institution></institution-wrap>Utrecht, The Netherlands</aff><aff id="Aff5"><label>5</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0444 9382</institution-id><institution-id institution-id-type="GRID">grid.10417.33</institution-id><institution>Centre for Molecular and Biomolecular Informatics,</institution><institution>Radboud University Medical Centre,</institution></institution-wrap>Nijmegen, The Netherlands</aff><aff id="Aff6"><label>6</label><institution-wrap><institution-id institution-id-type="ISNI">0000000120346234</institution-id><institution-id institution-id-type="GRID">grid.5477.1</institution-id><institution>Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine,</institution><institution>Utrecht University,</institution></institution-wrap>Utrecht, The Netherlands</aff></contrib-group><pub-date pub-type="epub"><day>10</day><month>2</month><year>2020</year></pub-date><pub-date pub-type="pmc-release"><day>10</day><month>2</month><year>2020</year></pub-date><pub-date pub-type="collection"><year>2020</year></pub-date><volume>21</volume><elocation-id>138</elocation-id><history><date date-type="received"><day>25</day><month>7</month><year>2019</year></date><date date-type="accepted"><day>4</day><month>2</month><year>2020</year></date></history><permissions><copyright-statement>© The Author(s). 2020</copyright-statement><license license-type="OpenAccess"><license-p><bold>Open Access</bold>This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/publicdomain/zero/1.0/">http://creativecommons.org/publicdomain/zero/1.0/</ext-link>) applies to the data made available in this article, unless otherwise stated.</license-p></license></permissions><abstract id="Abs1"><sec><title>Background</title><p id="Par1">We investigated the association of symptoms and disease severity of shigellosis patients with genetic determinants of infecting <italic>Shigella</italic> and entero-invasive <italic>Escherichia coli</italic> (EIEC), because determinants that predict disease outcome per individual patient could be used to prioritize control measures. For this purpose, genome wide association studies (GWAS) were performed using presence or absence of single genes, combinations of genes, and k-mers. All genetic variants were derived from draft genome sequences of isolates from a multicenter cross-sectional study conducted in the Netherlands during 2016 and 2017. Clinical data of patients consisting of binary/dichotomous representation of symptoms and their calculated severity scores were also available from this study. To verify the suitability of the methods used, the genetic differences between the genera <italic>Shigella</italic> and <italic>Escherichia</italic> were used as control.</p></sec><sec><title>Results</title><p id="Par2">The isolates obtained were representative of the population structure encountered in other Western European countries. No association was found between single genes or combinations of genes and separate symptoms or disease severity scores. Our benchmark characteristic, genus, resulted in eight associated genes and > 3,000,000 k-mers, indicating adequate performance of the algorithms used.</p></sec><sec><title>Conclusions</title><p id="Par3">To conclude, using several microbial GWAS methods, genetic variants in <italic>Shigella spp.</italic> and EIEC that can predict specific symptoms or a more severe course of disease were not identified, suggesting that disease severity of shigellosis is dependent on other factors than the genetic variation of the infecting bacteria. Specific genes or gene fragments of isolates from patients are unsuitable to predict outcomes and cannot be used for development, prioritization and optimization of guidelines for control measures of shigellosis or infections with EIEC.</p></sec></abstract><kwd-group xml:lang="en"><title>Keywords</title><kwd>GWAS</kwd><kwd>Shigellosis</kwd><kwd><italic>Shigella</italic></kwd><kwd>EIEC</kwd><kwd><italic>Escherichia coli</italic></kwd><kwd><italic>E. coli</italic></kwd><kwd>Disease severity</kwd><kwd>Symptoms</kwd><kwd>Disease control guidelines</kwd></kwd-group><funding-group><award-group><funding-source><institution-wrap><institution-id institution-id-type="FundRef">http://dx.doi.org/10.13039/501100003246</institution-id><institution>Nederlandse Organisatie voor Wetenschappelijk Onderzoek</institution></institution-wrap></funding-source><award-id>864.14.004</award-id><principal-award-recipient><name><surname>Dutilh</surname><given-names>Bas E.</given-names></name></principal-award-recipient></award-group></funding-group><funding-group><award-group><funding-source><institution>Dutch National Insitute for Public Health and the Environment for local Public Health Services</institution></funding-source><award-id>Not applicable</award-id></award-group></funding-group><custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name><meta-value>© The Author(s) 2020</meta-value></custom-meta></custom-meta-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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