No abstract

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.

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.

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.

Terpene synthases are widely distributed among microorganisms and have been mainly studied in members of the genus Streptomyces. However, little is known about the distribution and evolution of the genes for terpene synthases. Here, we performed whole-genome based phylogenetic analysis of Streptomyces species, and compared the distribution of terpene synthase genes among them. Overall, our study revealed that ten major types of terpene synthases are present within the genus Streptomyces, namely those for geosmin, 2-methylisoborneol, epi-isozizaene, 7-epi-α-eudesmol, epi-cubenol, caryolan-1-ol, cyclooctat-9-en-7-ol, isoafricanol, pentalenene and α-amorphene. The Streptomyces species divide in three phylogenetic groups based on their whole genomes for which the distribution of the ten terpene synthases was analysed. Geosmin synthases were the most widely distributed and were found to be evolutionary positively selected. Other terpene synthases were found to be specific for one of the three clades or a subclade within the genus Streptomyces. A phylogenetic analysis of the most widely distributed classes of Streptomyces terpene synthases in comparison to the phylogenomic analysis of this genus is discussed.

Phenotypic screening is a powerful approach to identify novel antibiotics, but elucidation of the targets responsible for the antimicrobial activity is often challenging in the case of compounds with a polypharmacological mode of action. Here, we show that activity-based protein profiling maps the target interaction landscape of a series of 1,3,4-oxadiazole-3-ones identified in a phenotypic screen to have high antibacterial potency against multidrug-resistant Staphylococcus aureus. In situ competitive and comparative chemical proteomics with a tailor-made activity-based probe, in combination with transposon and resistance studies, revealed several cysteine and serine hydrolases as relevant targets. Our data showcase oxadiazolones as a novel antibacterial chemotype with a polypharmacological mode of action, in which FabH, FphC, and AdhE play a central role.

No abstract

The chemically mutagenized Escherichia coli strain AS19 was isolated on the basis of its enhanced sensitivity to different antibiotics, in particular to actinomycin. The strain was later modified to study rRNA modifications that confer antibiotic resistance. Here, we present the genome sequence of the variant E. coli AS19-RrmA-.