Chemistry & Biology
Volume 16, Issue 8, 28 August 2009, Pages 826-836
Journal home page for Chemistry & Biology

Article
A Staphylococcus aureus Fitness Test Platform for Mechanism-Based Profiling of Antibacterial Compounds

https://doi.org/10.1016/j.chembiol.2009.07.004Get rights and content
Under an Elsevier user license
open archive

Summary

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 (Huber et al., 2009), demonstrate its use in the discovery of new cell wall inhibitors.

CHEMBIO
MICROBIO

Cited by (0)

2

Present address: ICx Biosystems, 505 Coast Boulevard South, Suite 309, La Jolla, CA 92037, USA

3

Present address: Semantic Laboratories, 8724-88 Villa La Jolla Drive, La Jolla, CA 92037, USA