Auxotrophic and prototrophic conditional genetic networks reveal the rewiring of transcription factors in Escherichia coli

Bacterial transcription factors (TFs) are widely studied in Escherichia coli . Yet it remains unclear how individual genes in the underlying pathways of TF machinery operate together during environmental challenge. Here, we address this by applying an unbiased, quantitative synthetic genetic interaction (GI) approach to measure pairwise GIs among all TF genes in E. coli under auxotrophic (rich medium) and prototrophic (minimal medium) static growth conditions. The resulting static and differential GI networks reveal condition-dependent GIs, widespread changes among TF genes in metabolism, and new roles for uncharacterized TFs ( yjdC , yneJ , ydiP ) as regulators of cell division, putrescine utilization pathway, and cold shock adaptation. Pan-bacterial conservation suggests TF genes with GIs are co-conserved in evolution. Together, our results illuminate the global organization of E. coli TFs, and remodeling of genetic backup systems for TFs under environmental change, which is essential for controlling the bacterial transcriptional regulatory circuits. The bacterium E. coli has around 300 transcriptional factors, but the functions of many of them, and the interactions between their respective regulatory networks, are unclear. Here, the authors study genetic interactions among all transcription factor genes in E. coli , revealing condition-dependent interactions and roles for uncharacterized transcription factors.