Global proteomic responses of Escherichia coli and evolution of biomarkers under tetracycline stress at acid and alkaline conditions

Abstract

The global proteomic regulation and the mechanism of biomolecule evolution in acid and alkaline ecosystems triggered by tetracycline, a representative of antibiotics, are not clear. To reveal the related mechanisms, the global responses of Escherichia (E.) coli to tetracycline in acid and alkaline conditions were analyzed using a proteomic approach. The specific phospholipid C16:1ω9c showed a significant decrease between the treatment and control groups. The 77 and 111 upregulated proteins in E. coli in acid and alkaline groups were mainly involved in carbohydrate transport and metabolism and energy metabolism, whereas, the 78 downregulated proteins were related to ribosome and bacterial chemotaxis in the acid group. The 110 downregulated proteins involved in carbon, glycine, serine, threonine, glyoxylate, and dicarboxylate metabolism, biosynthesis of antibiotics, fatty acids, and secondary metabolites in the alkaline group. Protein sequence analysis showed that the respective distribution of phosphorylation, glycosylation, and methylation sites among stable-expressed, upregulated, and downregulated proteins all showed a significant difference. TolC and phosphoenolpyruvate carboxykinase (Pck) in E. coli could be biomarkers to reflect tetracycline stress under extreme conditions with high sequence homology in Homo sapiens, implying the potential impact of tetracycline on humans at the network level. Generally, E. coli in the acid group accelerated the highly efficient protection mechanism to defend against tetracycline stress, while E. coli in the alkaline group strongly impaired the protection mechanism. These findings provide important clues to reveal the microbial antibiotic resistance mechanism in E. coli under extreme conditions and perfect the antibiotic usage.