Genome-wide screen to identify Escherichia coli gene knockouts hypersensitive to trimethoprim and chloramphenicol. Top left: Schematic showing the screening strategy for identifying hypersensitive gene knockouts from the Keio mutant library. All mutants were cultured in LB and LB supplemented with trimethoprim (TMP) and chloramphenicol (CMP) at their respective IC50s. Top right: Distribution of drug-susceptibilities of Keio mutants grown in indicated growth media obtained after normalizing the growth of each mutant to wild type (set to 1). Mean ± S.D. derived after fitting each distribution to a Gaussian function are shown. Bottom left: Analysis of gene functional categories for hypersensitive mutants compared with the frequency of genes in each category encoded by E. coli K-12 MG1655. Percentage of the total in each case is provided above each bar. Bottom right: Comparison of hypersensitive mutants identified in the trimethoprim and chloramphenicol screens shown as a Venn diagram. Representative genes from each set are named and gene names are colored by functional categories.
Intrinsic resistance pathways & #ResistanceBreaking. Study shows that inhibiting efflux pumps & cell envelope biogenesis sensitizes #bacteria to #antibiotics, but rapid evolutionary recovery may limit long-term effectiveness of resistance-breaking strategies #AMR @plosbiology.org 🧪 plos.io/4huAtvo