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Genomic Insights into the Distribution and Phylogeny of Glycopeptide Resistance Determinants within the

Andrés Andreo-Vidal1, Elisa Binda1, Victor Fedorenko2

  • 1Department of Biotechnology and Life Sciences, University of Insubria, 21100 Varese, Italy.

Antibiotics (Basel, Switzerland)
|December 24, 2021
PubMed

Insights

Antimicrobial resistance (AMR) threatens global health security. This study reveals van-like genes (vlgs), linked to glycopeptide antibiotic resistance, are widespread in Actinobacteria, even in non-producers, highlighting their potential role in AMR.

Area of Science:

  • Microbiology
  • Genomics
  • Bioinformatics

Background:

  • Antimicrobial resistance (AMR) poses a significant global health threat, diminishing antibiotic efficacy.
  • Glycopeptide antibiotics (GPAs), including vancomycin, are crucial last-resort treatments against multidrug-resistant (MDR) Gram-positive pathogens.
  • Emerging resistance to GPAs jeopardizes their clinical utility, necessitating an understanding of resistance origins.

Purpose of the Study:

  • To investigate the distribution and evolutionary history of glycopeptide antibiotic resistance determinants (van genes) within the Actinobacteria phylum.
  • To explore the presence and arrangement of van-like genes (vlgs) in both GPA-producing and non-producing actinobacteria.
  • To understand the phylogenetic relationships and co-evolutionary patterns of these resistance genes.

Main Methods:

  • Comprehensive bioinformatics analysis of actinobacterial genomes.
  • Phylogenetic reconstruction of van-like genes (vlgs).
  • Identification and characterization of van gene arrangements and associated biosynthetic gene clusters (BGCs).

Main Results:

  • Van-like genes (vlgs) were detected in over 10% of screened actinobacterial genomes, including non-producers of GPAs.
  • Less than 1% of these genomes encoded for a complete biosynthetic gene cluster (BGC) for GPAs.
  • Phylogenetic analyses revealed co-evolution of different vlgs, with vanY carboxypeptidase genes being the most prevalent, often found with vanS/R regulatory pairs.

Conclusions:

  • Van-like genes (vlgs) are widely distributed across the Actinobacteria phylum, suggesting a broader role beyond GPA production.
  • The presence of vlgs in non-GPA-producing bacteria indicates potential horizontal gene transfer or alternative functions.
  • Understanding the phylogeny and distribution of these resistance determinants is crucial for combating the spread of antimicrobial resistance.
Keywords:
antibiotic resistanceglycopeptide antibioticsmultidrug resistancevan genes

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