Investigation of co-expression network of eptA colistin resistance gene in Escherichia coli

Colistin (polymyxin E) is a polymyxin antibiotic. Polymyxin is increasingly used as a last resort antibiotic for the treatment of drug-resistant Gram-negative bacteria. Colistin makes the outer membrane of the bacteria permeable and disturbs the integrity of the inner membrane and finally causes cell death. Lipid A lipopolysaccharide is a main component of the outer membrane of most Gram-negative bacteria, and some bacteria induce resistance to colistin by making changes in its structure. Lipid A phosphorethanolamine transferase (eptA) is an enzyme responsible for modifying lipid A in E. Coli. In order to investigate the process of genes involved in resistance to colistin, a co-expression network consisting of 29 genes was reconstructed. Gene ontology analysis showed that lipid synthesis pathways involved in bacterial membrane structure such as liposaccharide biosynthesis, glycolipid biosynthesis and phospholipid biosynthesis have the highest number of representatives in the network. Network topology analysis showed that pagP had the highest number of connections with 27 direct connections. Next, eptB, arnT, basS and phoP genes were in the next row with 26 connections each. Also, pagP showed the highest betweenness centrality and closeness centrality with (0.03527178) and (1) respectively. Also, eptB is the second key gene in this network from the perspective of Closeness Centrality and Betweenness Centrality with (0.96428571) and (0.03332764). The classification of the genes in the network showed that out of the twelve differentiated groups, eptB was found in 8 groups and pagP was observed in only two groups. This shows that eptB, along with eptA, plays a key role in the induction of colistin resistance.