Chapter 1. Approaches to discovering novel antibacterial and antifungal agents.

The need for novel antibiotics to fight multidrug-resistant pathogens calls for a return to natural product screening, but novel approaches must be implemented to increase the chances of discovering novel compounds. This chapter illustrates strategic considerations and the required ingredients for screening programs: microbial diversity, samples for screening, targets and assays, assay development and implementation, hit identification and follow-up. When appropriate, we highlight the impact that chemical diversity consisting of mixtures of different compounds, amid a large background of known antibiotics, has on the screening process. Examples of detailed procedures are described for strain isolation and preservation, sample preparation, primary and secondary assays, and extract fractionation. While these limited examples are not sufficient to organize a complete screening program, they provide a basis for understanding the details of microbial product screening in the anti-infective field.