Of the ∼4,400 genes that constitute Escherichia coli's genome, ∼300 genes are indispensable for its growth in nutrient-rich conditions. These encode housekeeping functions including cell wall, DNA, RNA and protein syntheses. Under conditions where nutrients are limited to a carbon source, nitrogen source, essential phosphates, and salts, more than 100 additional genes become essential. These largely code for the synthesis of amino acids, vitamins, and nucleobases. While much is known about this collection of ∼400 genes, their interactions under nutrient stress are uncharted. Using a chemical biology approach, we focused on 45 chemical probes targeting encoded proteins in this collection, and mapped their interactions under nutrient-limited conditions. Encompassing 990 unique pairwise chemical combinations, we revealed a highly-connected network of 186 interactions, where 81 were synergistic and 105 were antagonistic. The network revealed signature interactions for each probe, and highlighted new connectivity between housekeeping functions and those essential in nutrient stress.


El Zahed SS, Brown ED.


iScience. 2018 Mar 27;2:168-181. doi: 10.1016/j.isci.2018.03.018.