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Co-PATHOgenex web application for assessing complex stress responses in pathogenic bacteria
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Science and Technology, Department of Physics. Integrated Science Lab (Icelab), Umeå University, Umeå, Sweden.
Umeå University, Faculty of Science and Technology, Department of Physics. Integrated Science Lab (Icelab), Umeå University, Umeå, Sweden.ORCID iD: 0000-0002-7181-9940
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Science and Technology, Department of Physics. Integrated Science Lab (Icelab), Umeå University, Umeå, Sweden.ORCID iD: 0000-0001-6874-6384
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2024 (English)In: Microbiology Spectrum, E-ISSN 2165-0497, Vol. 12, no 1, article id e02781-23Article in journal (Refereed) Published
Abstract [en]

Pathogenic bacteria encounter various stressors while residing in the host. They respond through intricate mechanisms of gene expression regulation, ensuring their survival and adaptation. Understanding how bacteria adapt to different stress conditions through regulatory processes of specific genes requires exploring complex transcriptional responses using gene co-expression networks. We employed a large transcriptome data set comprising 32 diverse human bacterial pathogens exposed to the same 11 host-mimicking stress conditions. Using the weighted gene co-expression network analysis algorithm, we generated bacterial gene co-expression networks. By associating modular eigengene expression with specific stress conditions, we identified gene co-expression modules and stress-specific stimulons, including genes with unique expression patterns under specific stress conditions. Suggesting a new potential role of the frm operon in responding to bile stress in enteropathogenic bacteria demonstrates the effectiveness of our approach. We also revealed the regulation of streptolysin S genes, involved in the production, processing, and export of streptolysin S, a toxin responsible for the beta-hemolytic phenotype of group A Streptococcus. In a comparative analysis of stress responses in three Escherichia coli strains from the core transcriptome, we revealed shared and unique expression patterns across the strains, offering insights into convergent and divergent stress responses. To help researchers perform similar analyses, we created the user-friendly web application Co-PATHOgenex. This tool aids in deepening our understanding of bacterial adaptation to stress conditions and in deciphering complex transcriptional responses of bacterial pathogens.IMPORTANCEUnveiling gene co-expression networks in bacterial pathogens has the potential for gaining insights into their adaptive strategies within the host environment. Here, we developed Co-PATHOgenex, an interactive and user-friendly web application that enables users to construct networks from gene co-expressions using custom-defined thresholds (https://avicanlab.shinyapps.io/copathogenex/). The incorporated search functions and visualizations within the tool simplify the usage and facilitate the interpretation of the analysis output. Co-PATHOgenex also includes stress stimulons for various bacterial species, which can help identify gene products not previously associated with a particular stress condition. Unveiling gene co-expression networks in bacterial pathogens has the potential for gaining insights into their adaptive strategies within the host environment. Here, we developed Co-PATHOgenex, an interactive and user-friendly web application that enables users to construct networks from gene co-expressions using custom-defined thresholds (https://avicanlab.shinyapps.io/copathogenex/). The incorporated search functions and visualizations within the tool simplify the usage and facilitate the interpretation of the analysis output. Co-PATHOgenex also includes stress stimulons for various bacterial species, which can help identify gene products not previously associated with a particular stress condition.

Place, publisher, year, edition, pages
American Society for Microbiology, 2024. Vol. 12, no 1, article id e02781-23
Keywords [en]
stress responses, bacterial pathogens, gene co-expression, stimulon, gene regulation, RNA-seq, transcriptomics
National Category
Microbiology in the medical area
Identifiers
URN: urn:nbn:se:umu:diva-217963DOI: 10.1128/spectrum.02781-23ISI: 001110226300001PubMedID: 38019016Scopus ID: 2-s2.0-85182501386OAI: oai:DiVA.org:umu-217963DiVA, id: diva2:1819684
Funder
Swedish Research Council, 2021-02466The Kempe FoundationsSwedish Research Council, 2018-02855Knut and Alice Wallenberg Foundation, 2016.0063Available from: 2023-12-14 Created: 2023-12-14 Last updated: 2024-01-25Bibliographically approved

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Fernández, LeydenRosvall, MartinNormark, JohanFällman, MariaAvican, Kemal

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Fernández, LeydenRosvall, MartinNormark, JohanFällman, MariaAvican, Kemal
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Department of Molecular Biology (Faculty of Medicine)Umeå Centre for Microbial Research (UCMR)Molecular Infection Medicine Sweden (MIMS)Department of PhysicsDepartment of Clinical Microbiology
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