Quantitative proteomic analysis reveals the mechanisms of polymyxin B toxicity to Escherichia coli

Abstract

Polymyxin B is increasingly employed all over the world to treat patients who affected by multidrug-resistant Gram-negative bacteria. Although the mechanism of resistance to polymyxin B is well known, the metabolic role of bacteria in stress response to polymyxin B remains an important task and may help to better understand polymyxin B-related stress response. In this study, the proteome changes of Escherichia coli (E. coli) continuously induced in concentrations of 1.0 mg/L and 10.0 mg/L polymyxin B were revealed. Compared to E. coli (PMB0), E. coli exposed to polymyxin B at 1.0 mg/L (PMB1) and 10.0 mg/L (PMB10) resulted in 89 and 314 differentially expressed proteins (DEPs), respectively. Such differences related to fatty acid degradation, quorum sensing and two-component regulatory system pathways. Based on absolute quantitative (iTRAQ) proteomics analysis, this study comprehensively studied the changes of E. coli proteome in culture with concentrations of 1.0 mg/L and 10.0 mg/L polymyxin B through confocal laser scanning microscopy observation, cell viability detection and reactive oxygen species analysis. The results showed that E. coli cultured at concentration of 10.0 mg/L polymyxin B increased the expression levels of multidrug-resistant efflux transporters and efflux pump membrane transporters, which might further improve the pathogens of polymyxin B-resistant bacteria lastingness and evolution. It has emerged globally to resist polymyxin B. The reuse of polymyxin B should be aroused public attention to avoid causing more serious environmental pollution. These findings could provide new insights into polymyxin B-related stress.