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


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.

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This work was supported by Grant No. 313599 from The Mexican National Council of Science and Technology (CONACYT) to MA, by VIDI grant 864.11.015 from the Netherlands Organization for Scientific Research (NWO) to PG and by grant 14221 from the Netherlands Organization for Scientific Research (NWO) to GPvW. We thank Hans Zweer for technical help with GC/Q-TOF analysis and Lisanne Storm for the help with the volatile antimicrobial screening, Yasuo Ohnishi and Le Zhang for sharing the glycine cleavage system mutants from S. griseus and S. coelicolor respectively, and Stephen Douthwaite for providing E. coli AS19-RlmA.

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Correspondence to Gilles P. van Wezel.

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Avalos, M., Garbeva, P., Raaijmakers, J.M. et al. Production of ammonia as a low-cost and long-distance antibiotic strategy by Streptomyces species. ISME J 14, 569–583 (2020).

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