Phenotypic Landscape of a Bacterial Cell
By R. Nichols, Śaunak Sen, Yoe-Jin Choo, Pedro Beltrão, Matylda Zietek, Rachna Chaba, Sueyoung Lee, K. Kazmierczak, Karis J. Lee, Angela Wong and 6 more. Cell, 2010
707 citations recorded by the source corpus.
Summary The explosion of sequence information in bacteria makes developing high-throughput, cost-effective approaches to matching genes with phenotypes imperative. Using E. coli as proof of principle, we show that combining large-scale chemical genomics with quantitative fitness measurements provides a high-quality data set rich in discovery. Probing growth profiles of a mutant library in hundreds of conditions in parallel yielded > 10,000 phenotypes that allowed us to study gene essentiality, discover leads for gene function and drug action, and understand higher-order organization of the bacterial chromosome. We highlight new information derived from the study, including insights into a gene involved in multiple antibiotic resistance and the synergy between a broadly used combinatory antibiotic therapy, trimethoprim and sulfonamides. This data set, publicly available at http://ecoliwiki.net/tools/chemgen/, is a valuable resource for both the microbiological and bioinformatic communities, as it provides high-confidence associations between hundreds of annotated and uncharacterized genes as well as inferences about the mode of action of several poorly understood drugs.
Subfields: Genetics, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/338f0f3171998b14d4963b04fafb1febc2b33d60
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Citations in the corpus
- Multidrug evolutionary strategies to reverse antibiotic resistance (2016, neutral): “drugs (115), nonoptimal gene regulation in the face of antibiotic inhibition results in a suppressive”
- Regulation by Small RNAs in Bacteria: Expanding Frontiers (2011, positive): “Alternatively, individual mutants can be arrayed such that a particular sRNA deletion can be compared to all other deletion strains under a wide range of conditions or easily moved into other mutant backgrounds (Nichols et al., 2011).”