Role of cellulose degradation products on Streptomyces development

Abstract

Cellulose-derived cello-oligosaccharides act as environmental signals in Streptomyces. In the phytopathogen Streptomyces scabiei, these molecules trigger thaxtomin A production, a major determinant of common scab, raising the question of how the bacterium discriminates between living host tissue and decaying environmental biomass. This study investigated the concentration dependent effects of cellobiose and cellotriose on S. scabiei and evaluated the extent to which this regulatory mechanism is conserved across saprophytic Streptomyces species. Cellulose degradation experiments first showed that cellobiose was the main soluble product released from the tested cellulose substrates, providing an experimentally relevant basis for studying its effects. Quantitative analyses revealed a non-linear concentration-dependent response in S. scabiei: low cello-oligosaccharide concentrations repressed thaxtomin A biosynthesis, whereas higher concentrations promoted its recovery and induction. Cellobiose also affected development, confining sporulation to a restricted intermediate concentration window. Proteomic analyses revealed extensive molecular remodeling, including the differential accumulation of key regulators such as BldM and WhiI, preceding the visible developmental phenotype. This supports a role for cellobiose as a quantitative signal rather than solely as a carbon source. To assess whether this response extends beyond the pathogenic species, 25 Streptomyces strains were screened across a cellobiose gradient. Streptomyces coelicolor displayed sequential blue and red pigmentation responses, typically associated with actinorhodin and prodiginine biosynthesis. Streptomyces reticuli exhibited a strictly concentration-dependent metabolic response. Multi-solvent extraction strategies in S. reticuli revealed a profound metabolic reprogramming and demonstrated that solvent selection heavily influences the detected metabolome. In parallel, in silico genome mining linked the macroscopic yellow pigmentation to the predicted induction of the antimicrobial naphthomycin A. Finally, in silico regulon predictions using the COMMBAT tool identified putative CebR-regulated biosynthetic pathways across the genus. However, structural modeling and comparison with LamR binding highlighted the limitations of purely sequence-based predictions on hybrid promoters. Overall, these results support a model in which cello-oligosaccharides act as quantitative environmental cues coordinating development, pathogenicity, and specialized metabolism in Streptomyces.