Production of ammonia as a low-cost and long-distance antibiotic strategy by Streptomyces species

• Published in: The ISME Journal Vol. 14; no. 2; pp. 569 - 583
• Main Authors: Avalos, Mariana, Garbeva, Paolina, Raaijmakers, Jos M., van Wezel, Gilles P.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.02.2020; Nature Publishing Group
• Subjects: 38; 38/91; 631/326/171/1818; 631/326/22/1290; Ammonia; Ammonia - metabolism; Anti-Bacterial Agents - metabolism; Anti-Bacterial Agents - pharmacology; Antibiosis; Antibiotics; Bacteria; Biomedical and Life Sciences; Biosynthesis; Deactivation; Drug Resistance, Microbial - physiology; E coli; Ecology; EnvZ protein; Escherichia coli - metabolism; Escherichia coli Proteins - metabolism; Evolutionary Biology; Glycine; Gram-negative bacteria; Gram-Negative Bacteria - drug effects; Gram-Positive Bacteria - drug effects; Inactivation; Kinases; Life Sciences; Low cost; Microbial Ecology; Microbial Genetics and Genomics; Microbial Interactions; Microbiology; Natural products; Soil dispersion; Soil Microbiology; Soils; Strategy; Streptomyces - metabolism; Streptomycetes; Volatiles
• ISSN: 1751-7362; 1751-7370
• DOI: 10.1038/s41396-019-0537-2

Soil-inhabiting streptomycetes are nature’s medicine makers, producing over half of all known antibiotics and many other bioactive natural products. However, these bacteria also produce many volatiles, molecules that disperse through the soil matrix and may impact other (micro)organisms from a distance. Here, we show that soil- and surface-grown streptomycetes have the ability to kill bacteria over long distances via air-borne antibiosis. Our research shows that streptomycetes do so by producing surprisingly high amounts of the low-cost volatile ammonia, dispersing over long distances to inhibit the growth of Gram-positive and Gram-negative bacteria. Glycine is required as precursor to produce ammonia, and inactivation of the glycine cleavage system nullified ammonia biosynthesis and concomitantly air-borne antibiosis. Reduced expression of the porin master regulator OmpR and its cognate kinase EnvZ is used as a resistance strategy by E. coli cells to survive ammonia-mediated antibiosis. Finally, ammonia was shown to enhance the activity of canonical antibiotics, suggesting that streptomycetes adopt a low-cost strategy to sensitize competitors for antibiosis from a distance.