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Published on: November 12, 2012
Elucidating the multi-drug resistance mechanism of Enterococcus faecalis V583: A gene interaction network analysis
Aniket Naha1, Sravan Kumar Miryala1, Reetika Debroy1
1Medical and Biological Computing Laboratory, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore 632014, Tamil Nadu, India.
Abstract:
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 (pbps, 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 pbps). Our results showed that the genes responsible for β-lactams resistance (pbp1A, 1C, 2A, 2B); glycopeptide resistance (ddl, vanBHBRBSBWXYB); Erythromycin, Macrolides, Lincosamide and Streptogramin-B (MLSB) resistance (msrA, EF_1680, EF_1682) along with mur genes (murABBCDEFG) 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.
Insights
Multi-drug resistant (MDR) bacteria pose a global threat. This study analyzes antimicrobial resistance (AMR) genes in Enterococcus faecalis V583, identifying key genes and mechanisms for potential new drug targets.
Area of Science:
- Microbiology
- Genetics
- Computational Biology
Background:
- The rise of multi-drug resistant (MDR) pathogenic bacterial strains, like Enterococcus faecalis V583, presents a significant global health challenge.
- Understanding the specific antimicrobial resistance (AMR) genes and their mechanisms is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the acquired exogenous AMR genes in Enterococcus faecalis V583.
- To construct and analyze an interaction network of AMR genes and their functional partners.
- To identify potential novel drug targets for combating antibiotic resistance.
Main Methods:
- Construction and analysis of an interaction network involving eight AMR genes and 40 functional partners.
- Functional enrichment analysis to identify genes involved in Cellular Component, Molecular Functions, and Biological Process.
- Clustering analysis to group genes associated with specific AMR mechanisms.
Main Results:
- Four distinct clusters of interconnected genes (C1-C4) were identified, linked to three primary AMR mechanisms: drug target alteration, target site bypass, and ABC transporter efflux pumps.
- Genes conferring resistance to beta-lactams, glycopeptides, and MLSB antibiotics, along with mur genes, were found to be critical in MDR.
- Network analysis revealed hub genes (mraY, pbpC, murE, murG, murD) with a high number of interactions, indicating their potential as drug targets.
Conclusions:
- The study elucidates the complex interplay of AMR genes in Enterococcus faecalis V583.
- Identified hub genes represent promising targets for the development of novel antimicrobial therapies.
- This research contributes to a deeper understanding of antibiotic resistance mechanisms and strategies for drug discovery.
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