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Progressive lung function decline is a hallmark of chronic obstructive pulmonary disease (COPD). Airway dysbiosis occurs in COPD, but whether it contributes to disease progression remains unknown. Here, we show, through a longitudinal analysis of two cohorts involving four UK centers, that baseline airway dysbiosis in COPD patients, characterized by the enrichment of opportunistic pathogenic taxa, associates with a rapid forced expiratory volume in 1 s (FEV 1) decline over 2 years. Dysbiosis associates with exacerbation-related FEV 1 fall and sudden FEV 1 fall at stability, contributing to long-term FEV 1 decline. A third cohort in China further validates the microbiota-FEV 1 -decline association. Human multi-omics and murine studies show that airway Staphylococcus aureus colonization promotes lung function decline through homocysteine, which elicits a neutrophil apoptosis-to-NETosis shift via the AKT1-S100A8/A9 axis. S. aureus depletion via bacteriophages restores lung function in emphysema mice, providing a fresh approach to slow COPD progression by targeting the airway microbiome. [Display omitted] • Baseline airway dysbiosis is associated with rapid lung function decline in COPD • Microbial-metabolite-host interactions differ in COPD rapid lung function decliners • Staphylococcus aureus impairs lung function via the homocysteine-AKT1-S100A8/A9 axis • Bacteriophage-targeting S. aureus restores lung function in emphysema mice Airway dysbiosis is associated with accelerated lung function decline, a hallmark feature in chronic obstructive pulmonary disease (COPD). Staphylococcus aureus impairs lung function via the homocysteine-AKT1-S100A8/A9 axis in emphysema mice, which can be rescued by bacteriophage targeting of this bacterium. These findings imply a translational application to slow COPD progression by targeting the microbiome. [ABSTRACT FROM AUTHOR]

In Arabidopsis , three lipase-like regulators, SAG101, EDS1, and PAD4, act downstream of resistance protein-associated defense signaling. Although the roles of SAG101, EDS1, and PAD4 in biotic stress have been extensively studied, little is known about their functions in plant responses to abiotic stresses. Here, we show that SAG101, EDS1, and PAD4 are involved in the regulation of freezing tolerance in Arabidopsis . With or without cold acclimation, the sag101 , eds1 , and pad4 single mutants, as well as their double mutants, exhibited similarly enhanced tolerance to freezing temperatures. Upon cold exposure, the sag101 , eds1 , and pad4 mutants showed increased transcript levels of C-REPEAT/DRE BINDING FACTORs and their regulons compared with the wild type. Moreover, freezing-induced cell death and accumulation of hydrogen peroxide were ameliorated in sag101 , eds1 , and pad4 mutants. The sag101 , eds1 , and pad4 mutants had much lower salicylic acid (SA) and diacylglycerol (DAG) contents than the wild type, and exogenous application of SA and DAG compromised the freezing tolerance of the mutants. Furthermore, SA suppressed the cold-induced expression of DGATs and DGKs in the wild-type leaves. These findings indicate that SAG101, EDS1, and PAD4 are involved in the freezing response in Arabidopsis , at least in part, by modulating the homeostasis of SA and DAG. [ABSTRACT FROM AUTHOR]