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Revealing 29 sets of independently modulated genes in Staphylococcus aureus, their regulators, and role in key physiological response

The ability of Staphylococcus aureus to infect many different tissue sites is enabled, in part, by its transcriptional regulatory network (TRN) that coordinates its gene expression to respond to different environments. We elucidated the organization and activity of this TRN by applying independent c...

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Autores principales: Poudel, Saugat, Tsunemoto, Hannah, Seif, Yara, Sastry, Anand V., Szubin, Richard, Xu, Sibei, Machado, Henrique, Olson, Connor A., Anand, Amitesh, Pogliano, Joe, Nizet, Victor, Palsson, Bernhard O.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382225/
https://www.ncbi.nlm.nih.gov/pubmed/32616573
http://dx.doi.org/10.1073/pnas.2008413117
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author Poudel, Saugat
Tsunemoto, Hannah
Seif, Yara
Sastry, Anand V.
Szubin, Richard
Xu, Sibei
Machado, Henrique
Olson, Connor A.
Anand, Amitesh
Pogliano, Joe
Nizet, Victor
Palsson, Bernhard O.
author_facet Poudel, Saugat
Tsunemoto, Hannah
Seif, Yara
Sastry, Anand V.
Szubin, Richard
Xu, Sibei
Machado, Henrique
Olson, Connor A.
Anand, Amitesh
Pogliano, Joe
Nizet, Victor
Palsson, Bernhard O.
author_sort Poudel, Saugat
collection PubMed
description The ability of Staphylococcus aureus to infect many different tissue sites is enabled, in part, by its transcriptional regulatory network (TRN) that coordinates its gene expression to respond to different environments. We elucidated the organization and activity of this TRN by applying independent component analysis to a compendium of 108 RNA-sequencing expression profiles from two S. aureus clinical strains (TCH1516 and LAC). ICA decomposed the S. aureus transcriptome into 29 independently modulated sets of genes (i-modulons) that revealed: 1) High confidence associations between 21 i-modulons and known regulators; 2) an association between an i-modulon and σS, whose regulatory role was previously undefined; 3) the regulatory organization of 65 virulence factors in the form of three i-modulons associated with AgrR, SaeR, and Vim-3; 4) the roles of three key transcription factors (CodY, Fur, and CcpA) in coordinating the metabolic and regulatory networks; and 5) a low-dimensional representation, involving the function of few transcription factors of changes in gene expression between two laboratory media (RPMI, cation adjust Mueller Hinton broth) and two physiological media (blood and serum). This representation of the TRN covers 842 genes representing 76% of the variance in gene expression that provides a quantitative reconstruction of transcriptional modules in S. aureus, and a platform enabling its full elucidation.
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spelling pubmed-73822252020-07-30 Revealing 29 sets of independently modulated genes in Staphylococcus aureus, their regulators, and role in key physiological response Poudel, Saugat Tsunemoto, Hannah Seif, Yara Sastry, Anand V. Szubin, Richard Xu, Sibei Machado, Henrique Olson, Connor A. Anand, Amitesh Pogliano, Joe Nizet, Victor Palsson, Bernhard O. Proc Natl Acad Sci U S A Biological Sciences The ability of Staphylococcus aureus to infect many different tissue sites is enabled, in part, by its transcriptional regulatory network (TRN) that coordinates its gene expression to respond to different environments. We elucidated the organization and activity of this TRN by applying independent component analysis to a compendium of 108 RNA-sequencing expression profiles from two S. aureus clinical strains (TCH1516 and LAC). ICA decomposed the S. aureus transcriptome into 29 independently modulated sets of genes (i-modulons) that revealed: 1) High confidence associations between 21 i-modulons and known regulators; 2) an association between an i-modulon and σS, whose regulatory role was previously undefined; 3) the regulatory organization of 65 virulence factors in the form of three i-modulons associated with AgrR, SaeR, and Vim-3; 4) the roles of three key transcription factors (CodY, Fur, and CcpA) in coordinating the metabolic and regulatory networks; and 5) a low-dimensional representation, involving the function of few transcription factors of changes in gene expression between two laboratory media (RPMI, cation adjust Mueller Hinton broth) and two physiological media (blood and serum). This representation of the TRN covers 842 genes representing 76% of the variance in gene expression that provides a quantitative reconstruction of transcriptional modules in S. aureus, and a platform enabling its full elucidation. National Academy of Sciences 2020-07-21 2020-07-02 /pmc/articles/PMC7382225/ /pubmed/32616573 http://dx.doi.org/10.1073/pnas.2008413117 Text en Copyright © 2020 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/ https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Biological Sciences
Poudel, Saugat
Tsunemoto, Hannah
Seif, Yara
Sastry, Anand V.
Szubin, Richard
Xu, Sibei
Machado, Henrique
Olson, Connor A.
Anand, Amitesh
Pogliano, Joe
Nizet, Victor
Palsson, Bernhard O.
Revealing 29 sets of independently modulated genes in Staphylococcus aureus, their regulators, and role in key physiological response
title Revealing 29 sets of independently modulated genes in Staphylococcus aureus, their regulators, and role in key physiological response
title_full Revealing 29 sets of independently modulated genes in Staphylococcus aureus, their regulators, and role in key physiological response
title_fullStr Revealing 29 sets of independently modulated genes in Staphylococcus aureus, their regulators, and role in key physiological response
title_full_unstemmed Revealing 29 sets of independently modulated genes in Staphylococcus aureus, their regulators, and role in key physiological response
title_short Revealing 29 sets of independently modulated genes in Staphylococcus aureus, their regulators, and role in key physiological response
title_sort revealing 29 sets of independently modulated genes in staphylococcus aureus, their regulators, and role in key physiological response
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382225/
https://www.ncbi.nlm.nih.gov/pubmed/32616573
http://dx.doi.org/10.1073/pnas.2008413117
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