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.

Gene
|April 28, 2020
PubMed

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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