Transcriptome and proteome exploration to model translation efficiency and protein stability in Lactococcus lactis

• Published in: PLoS computational biology Vol. 5; no. 12; p. e1000606
• Main Authors: Dressaire, Clémentine, Gitton, Christophe, Loubière, Pascal, Monnet, Véronique, Queinnec, Isabelle, Cocaign-Bousquet, Muriel
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.12.2009; Public Library of Science (PLoS)
• Subjects: Amino Acids - metabolism; Bacteria; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Biology; Computational Biology/Systems Biology; Efficiency; Gene Expression Profiling - methods; Genetic aspects; Genomes; Growth rate; Health aspects; Lactococcus; Lactococcus lactis; Lactococcus lactis - genetics; Lactococcus lactis - metabolism; Lactococcus lactis - physiology; Mathematical models; Microbiology; Models, Biological; Peptides; Protein Stability; Proteins; Proteome - genetics; Proteome - metabolism; Proteomics; Proteomics - methods; Ratios; Regulation; Software; Studies; Systems Biology - methods; France; Lactococcus lactis; Models, Biological; Proteomics; Proteome; Gene Expression Profiling; Protein Stability; Systems Biology; Amino Acids; Bacterial Proteins
• ISSN: 1553-7358; 1553-734X; 1553-7358
• DOI: 10.1371/journal.pcbi.1000606

This genome-scale study analysed the various parameters influencing protein levels in cells. To achieve this goal, the model bacterium Lactococcus lactis was grown at steady state in continuous cultures at different growth rates, and proteomic and transcriptomic data were thoroughly compared. Ratios of mRNA to protein were highly variable among proteins but also, for a given gene, between the different growth conditions. The modeling of cellular processes combined with a data fitting modeling approach allowed both translation efficiencies and degradation rates to be estimated for each protein in each growth condition. Estimated translational efficiencies and degradation rates strongly differed between proteins and were tested for their biological significance through statistical correlations with relevant parameters such as codon or amino acid bias. These efficiencies and degradation rates were not constant in all growth conditions and were inversely proportional to the growth rate, indicating a more efficient translation at low growth rate but an antagonistic higher rate of protein degradation. Estimated protein median half-lives ranged from 23 to 224 min, underlying the importance of protein degradation notably at low growth rates. The regulation of intracellular protein level was analysed through regulatory coefficient calculations, revealing a complex control depending on protein and growth conditions. The modeling approach enabled translational efficiencies and protein degradation rates to be estimated, two biological parameters extremely difficult to determine experimentally and generally lacking in bacteria. This method is generic and can now be extended to other environments and/or other micro-organisms.