| Title |
A Staphylococcus aureus Fitness Test Platform for Mechanism-Based Profiling of Antibacterial Compounds
|
|---|---|
| Published in |
Chemistry & Biology, August 2009
|
| DOI | 10.1016/j.chembiol.2009.07.004 |
| Pubmed ID | |
| Authors |
Robert G.K. Donald, Stephen Skwish, R. Allyn Forsyth, Jennifer W. Anderson, Tanya Zhong, Colleen Burns, Suzy Lee, Xin Meng, Lynn LoCastro, Lisa Wang Jarantow, Jesus Martin, Sang Ho Lee, Ian Taylor, David Robbins, Cheryl Malone, Liangsu Wang, Carlos S. Zamudio, Philip J. Youngman, John W. Phillips |
| 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 (Huber et al., 2009), demonstrate its use in the discovery of new cell wall inhibitors. |
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Mendeley demographics
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | <1% |
| Portugal | 1 | <1% |
| Japan | 1 | <1% |
| Israel | 1 | <1% |
| Indonesia | 1 | <1% |
| Unknown | 126 | 96% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 33 | 25% |
| Researcher | 27 | 21% |
| Student > Doctoral Student | 11 | 8% |
| Student > Bachelor | 11 | 8% |
| Student > Master | 11 | 8% |
| Other | 19 | 15% |
| Unknown | 19 | 15% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 56 | 43% |
| Biochemistry, Genetics and Molecular Biology | 25 | 19% |
| Immunology and Microbiology | 8 | 6% |
| Chemistry | 6 | 5% |
| Chemical Engineering | 2 | 2% |
| Other | 12 | 9% |
| Unknown | 22 | 17% |