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Joint sequencing of human and pathogen genomes reveals the genetics of pneumococcal meningitis

Streptococcus pneumoniae is a common nasopharyngeal colonizer, but can also cause life-threatening invasive diseases such as empyema, bacteremia and meningitis. Genetic variation of host and pathogen is known to play a role in invasive pneumococcal disease, though to what extent is unknown. In a gen...

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Autores principales: Lees, John A., Ferwerda, Bart, Kremer, Philip H. C., Wheeler, Nicole E., Serón, Mercedes Valls, Croucher, Nicholas J., Gladstone, Rebecca A., Bootsma, Hester J., Rots, Nynke Y., Wijmega-Monsuur, Alienke J., Sanders, Elisabeth A. M., Trzciński, Krzysztof, Wyllie, Anne L., Zwinderman, Aeilko H., van den Berg, Leonard H., van Rheenen, Wouter, Veldink, Jan H., Harboe, Zitta B., Lundbo, Lene F., de Groot, Lisette C. P. G. M., van Schoor, Natasja M., van der Velde, Nathalie, Ängquist, Lars H., Sørensen, Thorkild I. A., Nohr, Ellen A., Mentzer, Alexander J., Mills, Tara C., Knight, Julian C., du Plessis, Mignon, Nzenze, Susan, Weiser, Jeffrey N., Parkhill, Julian, Madhi, Shabir, Benfield, Thomas, von Gottberg, Anne, van der Ende, Arie, Brouwer, Matthijs C., Barrett, Jeffrey C., Bentley, Stephen D., van de Beek, Diederik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6520353/
https://www.ncbi.nlm.nih.gov/pubmed/31092817
http://dx.doi.org/10.1038/s41467-019-09976-3
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author Lees, John A.
Ferwerda, Bart
Kremer, Philip H. C.
Wheeler, Nicole E.
Serón, Mercedes Valls
Croucher, Nicholas J.
Gladstone, Rebecca A.
Bootsma, Hester J.
Rots, Nynke Y.
Wijmega-Monsuur, Alienke J.
Sanders, Elisabeth A. M.
Trzciński, Krzysztof
Wyllie, Anne L.
Zwinderman, Aeilko H.
van den Berg, Leonard H.
van Rheenen, Wouter
Veldink, Jan H.
Harboe, Zitta B.
Lundbo, Lene F.
de Groot, Lisette C. P. G. M.
van Schoor, Natasja M.
van der Velde, Nathalie
Ängquist, Lars H.
Sørensen, Thorkild I. A.
Nohr, Ellen A.
Mentzer, Alexander J.
Mills, Tara C.
Knight, Julian C.
du Plessis, Mignon
Nzenze, Susan
Weiser, Jeffrey N.
Parkhill, Julian
Madhi, Shabir
Benfield, Thomas
von Gottberg, Anne
van der Ende, Arie
Brouwer, Matthijs C.
Barrett, Jeffrey C.
Bentley, Stephen D.
van de Beek, Diederik
author_facet Lees, John A.
Ferwerda, Bart
Kremer, Philip H. C.
Wheeler, Nicole E.
Serón, Mercedes Valls
Croucher, Nicholas J.
Gladstone, Rebecca A.
Bootsma, Hester J.
Rots, Nynke Y.
Wijmega-Monsuur, Alienke J.
Sanders, Elisabeth A. M.
Trzciński, Krzysztof
Wyllie, Anne L.
Zwinderman, Aeilko H.
van den Berg, Leonard H.
van Rheenen, Wouter
Veldink, Jan H.
Harboe, Zitta B.
Lundbo, Lene F.
de Groot, Lisette C. P. G. M.
van Schoor, Natasja M.
van der Velde, Nathalie
Ängquist, Lars H.
Sørensen, Thorkild I. A.
Nohr, Ellen A.
Mentzer, Alexander J.
Mills, Tara C.
Knight, Julian C.
du Plessis, Mignon
Nzenze, Susan
Weiser, Jeffrey N.
Parkhill, Julian
Madhi, Shabir
Benfield, Thomas
von Gottberg, Anne
van der Ende, Arie
Brouwer, Matthijs C.
Barrett, Jeffrey C.
Bentley, Stephen D.
van de Beek, Diederik
author_sort Lees, John A.
collection PubMed
description Streptococcus pneumoniae is a common nasopharyngeal colonizer, but can also cause life-threatening invasive diseases such as empyema, bacteremia and meningitis. Genetic variation of host and pathogen is known to play a role in invasive pneumococcal disease, though to what extent is unknown. In a genome-wide association study of human and pathogen we show that human variation explains almost half of variation in susceptibility to pneumococcal meningitis and one-third of variation in severity, identifying variants in CCDC33 associated with susceptibility. Pneumococcal genetic variation explains a large amount of invasive potential (70%), but has no effect on severity. Serotype alone is insufficient to explain invasiveness, suggesting other pneumococcal factors are involved in progression to invasive disease. We identify pneumococcal genes involved in invasiveness including pspC and zmpD, and perform a human-bacteria interaction analysis. These genes are potential candidates for the development of more broadly-acting pneumococcal vaccines.
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spelling pubmed-65203532019-05-20 Joint sequencing of human and pathogen genomes reveals the genetics of pneumococcal meningitis Lees, John A. Ferwerda, Bart Kremer, Philip H. C. Wheeler, Nicole E. Serón, Mercedes Valls Croucher, Nicholas J. Gladstone, Rebecca A. Bootsma, Hester J. Rots, Nynke Y. Wijmega-Monsuur, Alienke J. Sanders, Elisabeth A. M. Trzciński, Krzysztof Wyllie, Anne L. Zwinderman, Aeilko H. van den Berg, Leonard H. van Rheenen, Wouter Veldink, Jan H. Harboe, Zitta B. Lundbo, Lene F. de Groot, Lisette C. P. G. M. van Schoor, Natasja M. van der Velde, Nathalie Ängquist, Lars H. Sørensen, Thorkild I. A. Nohr, Ellen A. Mentzer, Alexander J. Mills, Tara C. Knight, Julian C. du Plessis, Mignon Nzenze, Susan Weiser, Jeffrey N. Parkhill, Julian Madhi, Shabir Benfield, Thomas von Gottberg, Anne van der Ende, Arie Brouwer, Matthijs C. Barrett, Jeffrey C. Bentley, Stephen D. van de Beek, Diederik Nat Commun Article Streptococcus pneumoniae is a common nasopharyngeal colonizer, but can also cause life-threatening invasive diseases such as empyema, bacteremia and meningitis. Genetic variation of host and pathogen is known to play a role in invasive pneumococcal disease, though to what extent is unknown. In a genome-wide association study of human and pathogen we show that human variation explains almost half of variation in susceptibility to pneumococcal meningitis and one-third of variation in severity, identifying variants in CCDC33 associated with susceptibility. Pneumococcal genetic variation explains a large amount of invasive potential (70%), but has no effect on severity. Serotype alone is insufficient to explain invasiveness, suggesting other pneumococcal factors are involved in progression to invasive disease. We identify pneumococcal genes involved in invasiveness including pspC and zmpD, and perform a human-bacteria interaction analysis. These genes are potential candidates for the development of more broadly-acting pneumococcal vaccines. Nature Publishing Group UK 2019-05-15 /pmc/articles/PMC6520353/ /pubmed/31092817 http://dx.doi.org/10.1038/s41467-019-09976-3 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Lees, John A.
Ferwerda, Bart
Kremer, Philip H. C.
Wheeler, Nicole E.
Serón, Mercedes Valls
Croucher, Nicholas J.
Gladstone, Rebecca A.
Bootsma, Hester J.
Rots, Nynke Y.
Wijmega-Monsuur, Alienke J.
Sanders, Elisabeth A. M.
Trzciński, Krzysztof
Wyllie, Anne L.
Zwinderman, Aeilko H.
van den Berg, Leonard H.
van Rheenen, Wouter
Veldink, Jan H.
Harboe, Zitta B.
Lundbo, Lene F.
de Groot, Lisette C. P. G. M.
van Schoor, Natasja M.
van der Velde, Nathalie
Ängquist, Lars H.
Sørensen, Thorkild I. A.
Nohr, Ellen A.
Mentzer, Alexander J.
Mills, Tara C.
Knight, Julian C.
du Plessis, Mignon
Nzenze, Susan
Weiser, Jeffrey N.
Parkhill, Julian
Madhi, Shabir
Benfield, Thomas
von Gottberg, Anne
van der Ende, Arie
Brouwer, Matthijs C.
Barrett, Jeffrey C.
Bentley, Stephen D.
van de Beek, Diederik
Joint sequencing of human and pathogen genomes reveals the genetics of pneumococcal meningitis
title Joint sequencing of human and pathogen genomes reveals the genetics of pneumococcal meningitis
title_full Joint sequencing of human and pathogen genomes reveals the genetics of pneumococcal meningitis
title_fullStr Joint sequencing of human and pathogen genomes reveals the genetics of pneumococcal meningitis
title_full_unstemmed Joint sequencing of human and pathogen genomes reveals the genetics of pneumococcal meningitis
title_short Joint sequencing of human and pathogen genomes reveals the genetics of pneumococcal meningitis
title_sort joint sequencing of human and pathogen genomes reveals the genetics of pneumococcal meningitis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6520353/
https://www.ncbi.nlm.nih.gov/pubmed/31092817
http://dx.doi.org/10.1038/s41467-019-09976-3
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