Elucidating the multi-drug resistance mechanism of Enterococcus faecalis V583: A gene interaction network analysis.

• Gene interaction network analysis of E. faecalis V583 AMR genes was constructed. • Clustering analysis resulted in 4 densely interconnected clusters. • Genes playing important roles in MDR mechanisms have been observed. • Genes related to efflux pumps, β-lactams and glycopeptide resistance were listed. • Genes with high direct interactions can be considered as potent drug targets. Resistance to antibiotics have created havoc around the globe due to the emergence of multi-drug resistant (MDR) pathogenic bacterial strains. To decipher this problem, a detailed understanding of the antimicrobial resistance (AMR) genes and their resistant mechanisms are obligatory. The present study is mainly focused on an opportunistic, nosocomial bacterial strain Enterococcus faecalis V583, which possess acquired exogenous AMR genes portraying resistance against Chloramphenicol, Tetracycline, Vancomycin, Linezolid, Ampicillin and other antibiotics. An interaction network of eight AMR genes along with 40 functional partners have been constructed and analysed. Functional enrichment analysis highlighted 20, 21 and 22 genes having significant roles in Cellular Component (CC), Molecular Functions (MF) and Biological Process (BP) respectively. Clustering analysis resulted in four densely interconnected clusters (C1-C4) which were associated with three AMR mechanisms that include the alteration in drug target (pbp s , mur and van genes), complete replacement/bypass of target sites (van genes) and ATP Binding Cassette (ABC) transporter efflux pump mechanisms (msrA, EF_1680, EF_1682 and pbp s). Our results showed that the genes responsible for β-lactams resistance (pbp1A, 1C , 2A, 2B); glycopeptide resistance (ddl, vanBH B R B S B WXY B); Erythromycin, Macrolides, Lincosamide and Streptogramin-B (MLS B) resistance (msrA, EF_1680, EF_1682) along with mur genes (murA B BCDEFG) played an important role in MDR mechanisms. Network analysis has shown the genes mraY, pbpC, murE, murG and murD possessed 26, 24, 23, 22 and 22 interactions respectively. With more number of direct interactions, these genes can be considered as hub genes that could be exploited as potential drug targets for new drug discovery. [ABSTRACT FROM AUTHOR]