Systematic elucidation of independently modulated genes inLactobacillus plantarumreveals a trade-off between secondary and primary metabolism

Abstract

Lactobacillus plantarumis a probiotic bacteria widely used in food and health industries, but its gene regulatory information is limited in existing databases, which impedes the research of its physiology and its applications. To obtain a better understanding of the transcriptional regulatory network ofL. plantarum, independent component analysis (ICA) of its transcriptomes was used to derive 45 sets of independently modulated genes (iModulons). Those iModulons were annotated for associated transcription factors (TFs) and functional pathways, and active iModulons in response to different growth conditions were identified and characterized in detail. Eventually, the analysis of iModulon activities reveals a trade-off between regulatory activities of secondary and primary metabolism inL. plantarum.

Proteome trade-off between primary and secondary metabolism shapes acid stress induced bacterial exopolysaccharide production

“…The proteins that were significantly up-or down-regulated at both pH 4.5 and 5.0 were extracted to perform the enrichment analysis for functional pathways, subcellular locations, and regulons. The upregulated proteins enriched in ATP-binding cassette (ABC) transporters, carbohydrate metabolism, and stress response, while the down-regulated proteins enriched in purine metabolism, ABC transporters, and biosynthesis of cofactors (Figure 4E), which were highly consistent with previous research on acid stress induced gene expression regulation of LP 12,14,15 . For subcellular locations, most up-regulated proteins (e.g., ABC transporters, stress response proteins, EPS biosynthetic proteins) were membrane proteins, while most downregulated proteins (e.g., enzymes in purine and pyrimidine metabolism) were located in the cytoplasm (Figure 4F).…”

“…Furthermore, the significantly negative correlations of A and C sectors with the U sector depicted an explicit proteome trade-off between primary and secondary metabolism (Figure 6CD), which was also reported in the elucidation of independently modulated genes (iModulons) in LP 14 . When the pH decreased from 6.5 to 4.5, the proteome resource occupied by energy metabolism and anabolism decreased, while more proteome resources were allocated to EPS biosynthetic pathway.…”

“…Regarding the regulation of EPS biosynthesis, Fur was found to be significantly down-regulated under acid stress, in agreement with previous studies suggesting that Fur directly or indirectly represses EPS biosynthesis 30,31,32 and mediates acid tolerance 33,34 . Besides, the systematic transcriptomic analysis of LP also indicated that Fur had significant correlations with acid stress and EPS biosynthetic genes 14 .…”

“…However, the up-regulation of EPS biosynthetic genes was not observed for LP CAUH2 strain under oxidative stress 13 . Subsequently, in our previous work, the analysis of independently modulated gene sets (iModulons) with transcriptomic samples of various conditions (e.g., acid stress, different carbon sources), for the first time, found an interesting trade-off relationship between the regulatory activities of primary metabolism and EPS biosynthesis 14 . Nevertheless, such trade-off has not been validated by the proteomic profiling of LP under acid stress yet 15 .…”