Platforms for antibiotic discovery

The pace of antibiotic discovery has slowed down while resistance to bacteria is increasing.Biofilms harbouring drug-tolerant persisters often lead to untreatable chronic infections.Looking for untapped sources, such as uncultured bacteria, and developing rapid dereplication are likely to resuscitate the natural product discovery platform.A focus on species-specific compounds will provide a discovery platform, as the probability of finding such molecules is higher than the probability of discovering broader-spectrum antimicrobial compounds.Establishing rules that guide the penetration of molecules into bacteria will revive the rational design and high-throughput screening of synthetic compounds.Prodrugs that form reactive molecules within bacterial cells are capable of broad-spectrum and sterilizing activity.