Physical interactions triggerStreptomycesto prey on yeast using natural products and lytic enzymes

Abstract

AbstractMicrobial predators obtain energy from killing other living cells. In this study, we present compelling evidence demonstrating that widely distributedStreptomycessoil bacteria, typically not considered as predators, possess the ability to detect and prey onSaccharomyces cerevisiae. Using fluorescence microscopy, we observed that predation is initiated by physical contact betweenStreptomyces lavendulaeYAKB-15 and yeast cells. Comparative transcriptomics data indicated that the interaction triggered the production of numerous lytic enzymes to digest all major components of the yeast cell wall. The production of various glucanases, mannosidases and chitinases was confirmed by proteomics and enzymatic activity measurements. In order to destabilise the yeast cell membrane and assimilate yeast,Streptomyces lavendulaeYAKB-15 induced production of cell-associated antifungal polyenes, namely pentamycin and filipin III, and cholesterol oxidase ChoD. In response, yeast downregulated protein synthesis and attempted to enter a quiescence-like state. We show that yeast predation is a common phenomenon inStreptomyces, including well-characterized strains such asStreptomyces peucetiusATCC 27952, where the interaction led to production of 14-hydroxyisochainin. Finally, gene inactivation studies lead us to propose a multidirectional assault model harbouring numerous redundancies that are not dependant on any single individual factor. Our results provide insights into the ecological role ofStreptomycesand highlight the utilization of predation as a mechanism to elicit the production of bioactive natural products for drug discovery.Significance StatementSoil is a rich environment for microbes, where they compete for space and resources.Streptomycesbacteria are well-known for their ability to synthesize natural products, particularly antibiotics, that are used in chemical defense against competing microbes. Here we show thatStreptomycesare, in fact, predatory bacteria. Upon encountering yeast cells,Streptomycesinitiate the production of numerous enzymes that digest the cell wall of yeast. In addition, the interaction triggers the production of natural products that destabilize the yeast cell membrane. Collectively these actions lead to the death of yeast cells and release of cellular building blocks thatStreptomycescan use as nutrients. The work fundamentally shifts the paradigm of howStreptomycesare perceived within the soil microbiome ecosystem.