Proteomic Analysis of the Colistin-resistant E. coli Clinical Isolate: Explorations of the Resistome

Abstract

Background: Antimicrobial resistance is a worldwide problem after the emergence of colistin resistance since it was the last option left to treat carbapenemase-resistant bacterial infections. The mcr gene and its variants are one of the causes for colistin resistance. Besides mcr genes, some other intrinsic genes are also involved in colistin resistance but still need to be explored. Objective: The aim of this study was to investigate differential proteins expression of colistin-resistant E. coli clinical isolate and to understand their interactive partners as future drug targets. Methods: In this study, we have employed the whole proteome analysis through LC-MS/MS. The advance proteomics tools were used to find differentially expressed proteins in the colistin-resistant Escherichia coli clinical isolate compared to susceptible isolate. Gene ontology and STRING were used for functional annotation and protein-protein interaction networks, respectively. Results: LC-MS/MS analysis showed overexpression of 47 proteins and underexpression of 74 proteins in colistin-resistant E. coli. These proteins belong to DNA replication, transcription and translational process; defense and stress related proteins; proteins of phosphoenol pyruvate phosphotransferase system (PTS) and sugar metabolism. Functional annotation and protein-protein interaction showed translational and cellular metabolic process, sugar metabolism and metabolite interconversion. Conclusion: We conclude that these protein targets and their pathways might be used to develop novel therapeutics against colistin-resistant infections. These proteins could unveil the mechanism of colistin resistance.

Colistin Resistance and Management of Drug Resistant Infections

“…Andrade et al [ 81 ] summarized the colistin action and its drug resistance mechanisms [ 81 – 83 ]. Recently a study explored the bunch of proteins has been involved in colistin resistance by proteomic and bioinformatics [ 33 ], which could be employed to explore future research questions in the field of colistin resistance.…”

“…Bacteria embedded in deeper layers of the bioflm seldom come into contact with antibiotics, due to the inability of these drugs to adequately penetrate into its deeper layers; this results in a 10-1000-fold higher MIC as compared to planktonic cells [35][36][37]. Most recently, our proteomics-based study on colistin-resistant E coli revealed that a panel of diferentially expressed proteins, which could be unveiled the mechanism of colistin resistance [33]. Tis study also suggested that these proteins and their pathways could be used to develop novel therapeutics against colistinresistant infections.…”

“…Biofilm-mediated antibiotic resistance is also a well-known phenomenon. Correlation between the biofilm-forming ability regulated by genes/proteins and colistin resistance in bacteria has been shown in several studies, which depicted their inter-relationships with the resistance phenotype [ 33 – 35 ]. Several bacterial species produced biofilms, which promote tolerance to antimicrobials and hinder their penetration.…”