Antibiotics as probes of biological complexity

The utility of antibiotics has largely been based on their therapeutic application. However, in addition to clinical use, antibiotics have served as vital agents in probing bacterial complexity. Although not principally regarded as tools for dissecting bacterial genetics and biochemistry, antibiotics have nonetheless proved indispensable to understanding such essential functions as cell-wall biogenesis, DNA biosynthesis and the translation process. Herein we provide an overarching account of recent and landmark instances in which antibiotics have yielded critical information regarding many bacterial processes. We also elaborate on the importance of antibiotics and new chemical probes to the comprehension of genetic networks in the future. Given that antibiotics were among the first small molecules used to methodically perturb and understand biological systems, the past, present and future of antibiotics as probes of bacterial complexity offer some illustrative lessons for the broader field of chemical biology. © 2011 Nature America, Inc. All rights reserved.