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Terpenoids have diverse bioecological roles in all kingdoms of life. Here we discuss the evolution and ecological functions of microbial terpenoids and their possible applications.

Microorganisms represent a large and still resourceful pool for the discovery of novel compounds to combat antibiotic resistance in human and animal pathogens. The ability of microorganisms to produce structurally diverse volatile compounds has been known for decades, yet their biological functions and antimicrobial activities have only recently attracted attention. Various studies revealed that microbial volatiles can act as infochemicals in long-distance cross-kingdom communication as well as antimicrobials in competition and predation. Here, we review recent insights into the natural functions and modes of action of microbial volatiles and discuss their potential as a new class of antimicrobials and modulators of antibiotic resistance.

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.