Author/Authors :
Robert G.K. Donald، نويسنده , , Stephen Skwish، نويسنده , , R. Allyn Forsyth، نويسنده , , Jennifer W. Anderson، نويسنده , , Tanya Zhong، نويسنده , , Colleen Burns، نويسنده , , Suzy Lee، نويسنده , , Xin Meng، نويسنده , , Lynn LoCastro، نويسنده , , Lisa Wang Jarantow، نويسنده , , Jesus Martin، نويسنده , , Sang Ho Lee، نويسنده , , Ian Taylor، نويسنده , , David Robbins، نويسنده , , Cheryl Malone، نويسنده , , Liangsu Wang، نويسنده , , Carlos S. Zam، نويسنده ,
Abstract :
The emergence of drug-resistant bacteria coupled with the limited discovery of novel chemical scaffolds and druggable targets inspires new approaches to antibiotic development. Here we describe a chemical genomics strategy based on 245 Staphylococcus aureus antisense RNA strains, each engineered for reduced expression of target genes essential for S. aureus growth. Attenuation of gene expression can sensitize cells to compounds that inhibit the activity of a gene product or associated process. Pools of strains grown competitively in the presence of bioactive compounds generate characteristic profiles of strain sensitivities reflecting compound mechanism of action. Here, we validate this approach with a structurally and mechanistically diverse set of reference antibiotics and, in the accompanying paper in this issue of Chemistry & Biology (), demonstrate its use in the discovery of new cell wall inhibitors.
