Abstract
Covering: 1942-2025Bacteriophages (phages) are obligate viruses that infect bacteria. The antibacterial effects of both phages and natural products shape microbial ecosystems and have yielded competing antibiotic strategies. Phages have also intersected many times with natural products research throughout the past century. To discover antiviral leads, natural products were screened for anti-phage activity. To discover new anti-cancer drugs, natural products were screened for the ability to trigger lysis by the λ prophage-indicating DNA damage. Now, the antibiotic resistance crisis motivates the study of natural products that can synergize with phages to improve antibacterial therapies. Beyond applications, these parallel natural "chemical" and "biological" antibacterial factors combine to shape microbial communities across our planet. Here, we provide a comprehensive overview of natural products that modulate phage activities. We discuss their mechanisms of action, and we present opportunities for future research.