Co-PATHOgenex web application for assessing complex stress responses in pathogenic bacteria

Abstract

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 β-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. IMPORTANCE 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.

BacSC: A general workflow for bacterial single-cell RNA sequencing data analysis

“…Since this test setup does not suffer from double-dipping, we used the Benjamini-Hochberg correction [53] to account for multiple comparisons, revealing 186 genes with corrected p-values of less than 0.05. To verify our findings, we used bulk sequencing results from the Co-PATHOgenex study [54], also testing differential expression between cells grown in balanced and iron-reduced conditions. Of note, in this study an abrupt iron limitation was artificially induced by the addition of the iron chelator 2,2’-bipyridine shortly before harvest.…”