Fig. 1.

A genome-wide screen identifies changes in gene expression that confer antibiotic resistance. (a) A library of Escherichia coli strains with genes deleted or overexpressed is pooled and plated as a lawn on agar. A drug spot is applied which creates a zone of growth inhibition. Members of the strain library with increased drug resistance grow inside the zone of inhibition (yellow colonies), and are picked and identified by DNA sequencing. (b) Photographs of assay plates for five example antibiotics (out of 31) illustrate that both gene deletion and overexpression can confer drug resistance, and the possible levels of resistance range from none at all (e.g., colistin), to modest (e.g., clindamycin, vancomycin), to very strong (e.g., penicillin, trimethoprim). Plate images for all antibiotics are shown in supplementary figure S1, Supplementary Material online.