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

Publication date: 15 August 2017
Source:Cell Reports, Volume 20, Issue 7
Author(s): Paul A. Jensen, Zeyu Zhu, Tim van Opijnen
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.

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Teaser

Jensen et al. interrogate stress responses in bacteria using genome-wide techniques and metabolic modeling. The authors find that phenotypic and transcriptional stress networks are distinct. Moreover, nutrient and antibiotic stresses respectively lead to coordinated and uncoordinated responses. Network models are thus key to understanding cellular responses, thereby aiding in predicting bacterial behavior.


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