Volume 18, Issue 8, Pages (August 2011)

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Volume 18, Issue 8, Pages 955-965 (August 2011) Discovery of Kibdelomycin, A Potent New Class of Bacterial Type II Topoisomerase Inhibitor by Chemical-Genetic Profiling in Staphylococcus aureus John W. Phillips, Michael A. Goetz, Scott K. Smith, Deborah L. Zink, Jon Polishook, Russell Onishi, Scott Salowe, Judyann Wiltsie, John Allocco, Janet Sigmund, Karen Dorso, Suzy Lee, Stephen Skwish, Mercedes de la Cruz, Jesús Martín, Francisca Vicente, Olga Genilloud, Jun Lu, Ronald E. Painter, Katherine Young, Karen Overbye, Robert G.K. Donald, Sheo B. Singh Chemistry & Biology Volume 18, Issue 8, Pages 955-965 (August 2011) DOI: 10.1016/j.chembiol.2011.06.011 Copyright © 2011 Elsevier Ltd Terms and Conditions

Chemistry & Biology 2011 18, 955-965DOI: (10. 1016/j. chembiol. 2011 Copyright © 2011 Elsevier Ltd Terms and Conditions

Figure 1 Two-Dimensional Cluster Analysis of S. aureus Fitness Test Profiles for the Crude Extract, Kibdelomycin, and Four Compounds of Known Mechanism of Action Strain depletions are depicted in magenta, strain resistances in cyan. The thresholds for including strains in the cluster analysis are >5-fold depletion, p-value ≤ 0.01 in at least 4 of the experiments for any one compound or extract. The compound name is followed by the treatment concentration. Profiles for the Crude Extract and Kibdelomycin cluster tightly with profiles of the antibiotic Novobiocin. The antisense strains targeting the 2 subunits of DNA gyrase (gyrA, gyrB) and DNA topoisomerase IV (parC, parE) are shown in red. Chemistry & Biology 2011 18, 955-965DOI: (10.1016/j.chembiol.2011.06.011) Copyright © 2011 Elsevier Ltd Terms and Conditions

Figure 2 Chemical Structure of Kibdelomycin Chemistry & Biology 2011 18, 955-965DOI: (10.1016/j.chembiol.2011.06.011) Copyright © 2011 Elsevier Ltd Terms and Conditions

Figure 3 Inhibition of Macromolecular Synthesis of Kibdelomycin Inhibitory effects across increasing concentrations were determined by measuring incorporation of radiolabeled precursors of either DNA (14C-thymidine), RNA (3H-uridine), phospholipid (2-3H-glycerol), protein (3H-leucine), or cell wall (14C-glycine) in S. aureus strain EP167. Chemistry & Biology 2011 18, 955-965DOI: (10.1016/j.chembiol.2011.06.011) Copyright © 2011 Elsevier Ltd Terms and Conditions