Nutrient deprived growth of Streptomyces promotes foraging growth and enhanced antimicrobial activity

Species of the genus Streptomyces are filamentous bacteria mainly residing in soils. The capacity of streptomycetes to adapt to various environments is reflected in the sheer size of their genomes and the number of encoded regulatory proteins. The nutrient-rich laboratory conditions used for culturing significantly differ from the conditions in the natural habitat of streptomycetes and fail to stimulate their full range of adaptive behaviors; as on of the results, the majority of biosynthetic gene clusters remain silent. Moreover, the use of rich media has led to the assumption that nutrient depletion ultimately promotes sporulation. However, we demonstrate that S. coelicolor colonies can respond to nutrient depletion by displaying a previously unidentified phenotypic transition termed “foraging” due to its submerged and continuous growth on depleted media. The foraging phenotype is distinctly different from conventional phenotypes in terms of colony morphology, genomic stability, and metabolomic profile. This adaptation to nutrient deprivation through foraging is found throughout the Streptomyces phylogeny, indicating that the phenotype is highly conserved. Furthermore, foraging S. coelicolor gains the ability to inhibit molds and enhanced competitive activity against both gram-negative and gram-positive bacteria is detected in other species. These findings highlight how morphological adaptations of streptomycetes in nutrient-limited environments alter secondary metabolite production, enabling the screening of novel antimicrobial activities. These discoveries have implications ranging from the basic biology of streptomycetes to drug discovery and microbial ecology.