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

ABSTRACT: 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 ?S, 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.

SUBMITTER: Poudel S

PROVIDER: S-EPMC7382225 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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

Poudel Saugat S Tsunemoto Hannah H Seif Yara Y Sastry Anand V AV Szubin Richard R Xu Sibei S Machado Henrique H Olson Connor A CA Anand Amitesh A Pogliano Joe J Nizet Victor V Palsson Bernhard O BO

Proceedings of the National Academy of Sciences of the United States of America 20200702 29

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 ...[more]

PMID: 32616573

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Dataset Information

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

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Revealing 29 sets of independently modulated genes in <i>Staphylococcus aureus</i>, their regulators, and role in key physiological response.

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