Umbrella toxin particles produced by Streptomyces block mycelial growth of competing species

Abstract

AbstractTheStreptomycesare a genus of ubiquitous soil bacteria from which the majority of clinically utilized antibiotics derive. The production of these antibacterial molecules reflects the relentless competitionStreptomycesengage in with other bacteria, including otherStreptomycesspecies. Here we show that in addition to small molecule antibiotics, Streptomyces produce and secrete antibacterial protein complexes that feature a large, degenerate repeat-containing polymorphic toxin protein. A cryo-EM structure of these particles reveals an extended stalk topped by a ringed crown comprising the toxin repeats scaffolding five lectin-tipped spokes, leading to our naming them umbrella particles.S. coelicolorencodes three umbrella particles with distinct toxin and lectin composition, and supernatant containing these toxins specifically and potently inhibits the growth of selectStreptomycesspecies from among a diverse collection of bacteria screened. For one target,S. griseus, we find inhibition relies on a single toxin and that intoxication manifests as rapid cessation of vegetative mycelial growth. Our data show thatStreptomycesumbrella particles mediate competition between vegetative mycelia of related species, a function distinct from small molecule antibiotics, which are produced at the onset of reproductive growth and act broadly. Sequence analyses suggest this role of umbrella particles extends beyondStreptomyces, as we find umbrella loci in nearly one-thousand species across Actinobacteria.