Streptomyces umbrella toxin particles block hyphal growth of competing species

Authors: ZHAO, QINQIN - University Of Washington; BERTOLLI, SAVANNAH - University Of Washington; PARK, YOUNG-JUN - University Of Washington; TAN, YONGIUN - St Louis University; CUTLER, KEVIN - University Of Washington; SRIVIVAS, POOJA - University Of Washington; ASFAHL, KYLE - University Of Washington; GARCIA, CITLALI - University Of California Berkeley; GALLAGHER, LARRY - University Of Washington; LI, YAQIAO - University Of Washington; WANG, YAXI - University Of Washington; Coleman-Derr, Devin; DIMAIO, FRANK - University Of Washington; ZHANG, F - St Louis University; PETERSON, S. - University Of Washington; VEESLER, DAVID - University Of Washington; MOUGOUS, JOSEPH - University Of Washington

Submitted to: Nature
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/11/2024
Publication Date: 4/17/2024
Citation: Zhao, Q., Bertolli, S., Park, Y., Tan, Y., Cutler, K., Srivivas, P., Asfahl, K., Garcia, C.F., Gallagher, L., Li, Y., Wang, Y., Coleman-Derr, D.A., DiMaio, F., Zhang, F., Peterson, S.B., Veesler, D., Mougous, J.D. 2024. Streptomyces umbrella toxin particles block hyphal growth of competing species. Nature. 629:165–173. https://doi.org/10.1038/s41586-024-07298-z.
DOI: https://doi.org/10.1038/s41586-024-07298-z

Interpretive Summary: The Streptomyces are a genus of ubiquitous soil bacteria from which the majority of clinically utilized antibiotics derive, and are known to closely associate with the roots of many crop plants. The production of these antibacterial molecules reflects the relentless competition Streptomyces engage in with other bacteria, including other Streptomyces species1,2. 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. This work has important implications for understanding Streptomyces biology, crop microbiomes and the development of tools for mitigating bacterial pathogen growth.

Technical Abstract: In this study, we show that Streptomyces produce and secrete antibacterial protein complexes that feature a large, degenerate repeat-containing polymorphic toxin protein. A cryoEM 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. coelicolor encodes three umbrella particles with distinct toxin and lectin composition, and supernatant containing these toxins specifically and potently inhibits the growth of select Streptomyces species 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 that Streptomyces umbrella 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 broadly3. Sequence analyses suggest this role of umbrella particles extends beyond Streptomyces, as we find umbrella loci in nearly one-thousand species across Actinobacteria.