Antibiotics Disrupt Coordination between Transcriptional and Phenotypic Stress Responses in Pathogenic Bacteria

Paul A. Jensen, Zeyu Zhu, Tim van Opijnen

Research output: Contribution to journalArticle

Abstract

Bacterial genes that change in expression upon environmental disturbance have commonly been seen as those that must also phenotypically matter. However, several studies suggest that differentially expressed genes are rarely phenotypically important. We demonstrate, for Gram-positive and Gram-negative bacteria, that these seemingly uncoordinated gene sets are involved in responses that can be linked through topological network analysis. However, the level of coordination is stress dependent. While a well-coordinated response is triggered in response to nutrient stress, antibiotics trigger an uncoordinated response in which transcriptionally and phenotypically important genes are neither linked spatially nor in their magnitude. Moreover, a gene expression meta-analysis reveals that genes with large fitness changes during stress have low transcriptional variation across hundreds of other conditions, and vice versa. Our work suggests that cellular responses can be understood through network models that incorporate regulatory and genetic relationships, which could aid drug target predictions and genetic network engineering.

Original languageEnglish (US)
Pages (from-to)1705-1716
Number of pages12
JournalCell Reports
Volume20
Issue number7
DOIs
StatePublished - Aug 15 2017

Keywords

  • Pseudomonas
  • RNA-seq
  • Streptococcus
  • Tn-seq
  • data integration
  • metabolic modeling
  • stress response
  • systems biology

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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