Time-resolved monitoring of yeast responses to lipopolysaccharide exposure by cell-released volatile organic compounds.

Volatile organic compound (VOC) profiles function as dynamic fingerprints of physiological states and disease progression. Here, the eukaryotic organism Saccharomyces cerevisiae was used to investigate the emission characteristics of VOCs induced by lipopolysaccharide (LPS). Using multi-omics techniques and physiology methods, yeast cells were observed to undergo both stress and adaptation phases upon exposure, as characterized by changes in acetic acid-D and higher alcohols/aldehydes. The oxidative phosphorylation process in yeast was inhibited during the stress response, leading to an oxidative stress accompanied by growth inhibition and cell wall remodeling. The adaptive stage of cells reprogrammed metabolism to consume excess metabolic substrates generated during the stress stage, thus resulting in the production of secondary metabolites such as higher alcohols/aldehydes as biomarkers. Acetic acid detected could, in contrast, serve as an early biomarker for the oxidative stress of yeast. Using flow cytometry together with FITC labeling, LPS was further shown to bind to cells, leading to internalization and membrane damage compared to controls. This study provides time-resolved mechanistic insights into VOCs as non-invasive biomarkers. These findings suggest that dynamic VOC profiles from cells hold promise as a "surveillance camera" for monitoring cellular health.IMPORTANCEThe analysis of metabolically derived volatile organic compounds (VOCs) provides an approach for tracking cellular stress dynamics. We demonstrate that the VOC profile released by S. cerevisiae cells dynamically evolved with time during lipopolysaccharide (LPS)-induced stress, coordinated with transcriptomic and proteomic reprogramming. Through multiple omics techniques and physiology, yeast cells were observed to undergo both stress and adaptation phases, as characterized by changes in acetic acid-D and higher alcohols/aldehydes. These findings establish VOCs as real-time, non-invasive indicators of time-resolved stress responses, highlighting their potential as surveillance tools to detect early cellular perturbations caused by external threats.