Fig. 2: Functional gene responses are different between starvation- and hypoxia-induced NRP.
a Proteins detected and quantified across time-course proteomic analyses of starvation- (green circle: 1102 proteins) and hypoxia-induced (blue circle: 966 proteins) NRP. A total of 379 proteins were quantified across all time points in both conditions. b Principal component analysis reveals distinct protein dynamics during starvation (green ellipse: S4, S10, and S20) and hypoxia (blue ellipse: W4, W9, and W18) responses. Protein observations are color-coded according to the functional category, as follows: red = lipid metabolism (e.g., acetyl-CoA metabolism, β-oxidation); orange = cholesterol metabolism (e.g., propionyl-CoA metabolism); green = cell wall, virulence, detoxification and adaptation; blue = redox homeostasis; magenta = regulatory proteins and information pathways; yellow = replication and translation. c Major metabolic differences between starvation- and hypoxia-induced NRP informed by proteomic datasets. While co-catabolism of carbon substrates appears to be a shared feature of both stresses, starvation significantly induces the upregulation of proteins with known functions in fatty acid metabolism. On the other hand, hypoxia coordinately induces the upregulation of proteins with documented roles in the metabolism of cholesterol and odd-chain fatty acids (e.g., enzymes involved in the methylmalonyl-CoA pathway (MCP) and methylcitrate cycle (MCC)).30 Importantly, starvation significantly decreased and hypoxia increased levels of isocitrate lyase (Icl), the key enzyme in the glyoxylate shunt. OXO oxaloacetate, CIT citrate, αKG α-ketoglutamate, SUC succinate, FUM fumarate, MAL malate. d–g Comparison of two-component system protein levels during hypoxia (red) and starvation (blue time courses. Plots contain individual log2(fold-change) data for 1–3 replicates, thick bars as mean values and thin bars as standard deviation on 0, 4, 9, and 19 days of hypoxia or starvation and after 6 days of resuscitation (R) with normoxia or nutrient restoration. Note: peptide signals for MtrB in hypoxia did not meet the cutoff criteria for proteomic quantitation but we have added the data in (e) for completeness. See Supplementary Data 4 for the source data used in these graphs.
