Abstract
Biological stress responses operate across multiple scales, yet the coordination mechanisms remain poorly characterized. Here, we present comprehensive systems-level characterization of coordinated plant and endophytic microbiome responses during xenobiotic stress, integrating ultrastructural analysis, proteomics, and microbiome profiling in rice seedlings exposed to ciprofloxacin. We discovered a sophisticated multi-level defense system with chloroplasts as a key hub within a highly integrated cross-organellar network, comprising 36% of all differentially expressed proteins. The system operates through 3 integrated mechanisms: (a) differential cellular accumulation patterns showing 14-fold tissue-specific differences, (b) reactive-oxygen-species-associated metabolic processes with reduced toxicity of transformation products, and (c) restructuring of endophytic bacterial communities toward stress-resistant genera. This work indicates that biological systems deploy hierarchical, integrated responses spanning from organellar to ecosystem levels. The chloroplast-centered response represents a comprehensive characterization of multicompartmental responses with implications across multiple biological fields. Our findings illustrate how multidisciplinary systems approaches can uncover emergent properties of multiscale biological responses invisible to single-scale analyses, providing a framework for investigating multiscale responses across diverse biological systems.