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Systems biology analysis of the Clostridioides difficile core-genome contextualizes microenvironmental evolutionary pressures leading to genotypic and phenotypic divergence

Hospital acquired Clostridioides (Clostridium) difficile infection is exacerbated by the continued evolution of C. difficile strains, a phenomenon studied by multiple laboratories using stock cultures specific to each laboratory. Intralaboratory evolution of strains contributes to interlaboratory va...

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Autores principales: Norsigian, Charles J., Danhof, Heather A., Brand, Colleen K., Oezguen, Numan, Midani, Firas S., Palsson, Bernhard O., Savidge, Tor C., Britton, Robert A., Spinler, Jennifer K., Monk, Jonathan M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576604/
https://www.ncbi.nlm.nih.gov/pubmed/33082337
http://dx.doi.org/10.1038/s41540-020-00151-9
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author Norsigian, Charles J.
Danhof, Heather A.
Brand, Colleen K.
Oezguen, Numan
Midani, Firas S.
Palsson, Bernhard O.
Savidge, Tor C.
Britton, Robert A.
Spinler, Jennifer K.
Monk, Jonathan M.
author_facet Norsigian, Charles J.
Danhof, Heather A.
Brand, Colleen K.
Oezguen, Numan
Midani, Firas S.
Palsson, Bernhard O.
Savidge, Tor C.
Britton, Robert A.
Spinler, Jennifer K.
Monk, Jonathan M.
author_sort Norsigian, Charles J.
collection PubMed
description Hospital acquired Clostridioides (Clostridium) difficile infection is exacerbated by the continued evolution of C. difficile strains, a phenomenon studied by multiple laboratories using stock cultures specific to each laboratory. Intralaboratory evolution of strains contributes to interlaboratory variation in experimental results adding to the challenges of scientific rigor and reproducibility. To explore how microevolution of C. difficile within laboratories influences the metabolic capacity of an organism, three different laboratory stock isolates of the C. difficile 630 reference strain were whole-genome sequenced and profiled in over 180 nutrient environments using phenotypic microarrays. The results identified differences in growth dynamics for 32 carbon sources including trehalose, fructose, and mannose. An updated genome-scale model for C. difficile 630 was constructed and used to contextualize the 28 unique mutations observed between the stock cultures. The integration of phenotypic screens with model predictions identified pathways enabling catabolism of ethanolamine, salicin, arbutin, and N-acetyl-galactosamine that differentiated individual C. difficile 630 laboratory isolates. The reconstruction was used as a framework to analyze the core-genome of 415 publicly available C. difficile genomes and identify areas of metabolism prone to evolution within the species. Genes encoding enzymes and transporters involved in starch metabolism and iron acquisition were more variable while C. difficile distinct metabolic functions like Stickland fermentation were more consistent. A substitution in the trehalose PTS system was identified with potential implications in strain virulence. Thus, pairing genome-scale models with large-scale physiological and genomic data enables a mechanistic framework for studying the evolution of pathogens within microenvironments and will lead to predictive modeling to combat pathogen emergence.
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spelling pubmed-75766042020-10-29 Systems biology analysis of the Clostridioides difficile core-genome contextualizes microenvironmental evolutionary pressures leading to genotypic and phenotypic divergence Norsigian, Charles J. Danhof, Heather A. Brand, Colleen K. Oezguen, Numan Midani, Firas S. Palsson, Bernhard O. Savidge, Tor C. Britton, Robert A. Spinler, Jennifer K. Monk, Jonathan M. NPJ Syst Biol Appl Article Hospital acquired Clostridioides (Clostridium) difficile infection is exacerbated by the continued evolution of C. difficile strains, a phenomenon studied by multiple laboratories using stock cultures specific to each laboratory. Intralaboratory evolution of strains contributes to interlaboratory variation in experimental results adding to the challenges of scientific rigor and reproducibility. To explore how microevolution of C. difficile within laboratories influences the metabolic capacity of an organism, three different laboratory stock isolates of the C. difficile 630 reference strain were whole-genome sequenced and profiled in over 180 nutrient environments using phenotypic microarrays. The results identified differences in growth dynamics for 32 carbon sources including trehalose, fructose, and mannose. An updated genome-scale model for C. difficile 630 was constructed and used to contextualize the 28 unique mutations observed between the stock cultures. The integration of phenotypic screens with model predictions identified pathways enabling catabolism of ethanolamine, salicin, arbutin, and N-acetyl-galactosamine that differentiated individual C. difficile 630 laboratory isolates. The reconstruction was used as a framework to analyze the core-genome of 415 publicly available C. difficile genomes and identify areas of metabolism prone to evolution within the species. Genes encoding enzymes and transporters involved in starch metabolism and iron acquisition were more variable while C. difficile distinct metabolic functions like Stickland fermentation were more consistent. A substitution in the trehalose PTS system was identified with potential implications in strain virulence. Thus, pairing genome-scale models with large-scale physiological and genomic data enables a mechanistic framework for studying the evolution of pathogens within microenvironments and will lead to predictive modeling to combat pathogen emergence. Nature Publishing Group UK 2020-10-20 /pmc/articles/PMC7576604/ /pubmed/33082337 http://dx.doi.org/10.1038/s41540-020-00151-9 Text en © The Author(s) 2020 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
Norsigian, Charles J.
Danhof, Heather A.
Brand, Colleen K.
Oezguen, Numan
Midani, Firas S.
Palsson, Bernhard O.
Savidge, Tor C.
Britton, Robert A.
Spinler, Jennifer K.
Monk, Jonathan M.
Systems biology analysis of the Clostridioides difficile core-genome contextualizes microenvironmental evolutionary pressures leading to genotypic and phenotypic divergence
title Systems biology analysis of the Clostridioides difficile core-genome contextualizes microenvironmental evolutionary pressures leading to genotypic and phenotypic divergence
title_full Systems biology analysis of the Clostridioides difficile core-genome contextualizes microenvironmental evolutionary pressures leading to genotypic and phenotypic divergence
title_fullStr Systems biology analysis of the Clostridioides difficile core-genome contextualizes microenvironmental evolutionary pressures leading to genotypic and phenotypic divergence
title_full_unstemmed Systems biology analysis of the Clostridioides difficile core-genome contextualizes microenvironmental evolutionary pressures leading to genotypic and phenotypic divergence
title_short Systems biology analysis of the Clostridioides difficile core-genome contextualizes microenvironmental evolutionary pressures leading to genotypic and phenotypic divergence
title_sort systems biology analysis of the clostridioides difficile core-genome contextualizes microenvironmental evolutionary pressures leading to genotypic and phenotypic divergence
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576604/
https://www.ncbi.nlm.nih.gov/pubmed/33082337
http://dx.doi.org/10.1038/s41540-020-00151-9
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