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Balancing the Virulence and Antimicrobial Resistance in VISA DAP-R CA-MRSA Superbug

Rossella Salemi1, Alessandra Zega1, Elvira Aguglia1

  • 1Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy.

Antibiotics (Basel, Switzerland)
|September 23, 2022
PubMed
Abstract

Insights

Community-acquired Methicillin-resistant Staphylococcus aureus (CA-MRSA) with vancomycin and daptomycin resistance (VISA DAP-R) emerged. Genomic analysis revealed adaptations balancing extensive antimicrobial resistance (AMR) with decreased virulence, suggesting a compensatory mutation.

Area of Science:

  • Microbiology
  • Genomics
  • Antimicrobial Resistance

Background:

  • Vancomycin-intermediate Staphylococcus aureus (VISA) strains are globally reported, predominantly in hospital-associated MRSA.
  • Community-acquired MRSA (CA-MRSA) rarely develops VISA, making VISA daptomycin-resistant (DAP-R) CA-MRSA emergence significant.
  • This study investigated genomic and transcriptomic adaptations in a VISA DAP-R CA-MRSA strain from a patient treated with glycopeptides.

Purpose of the Study:

  • To explore the genomic and transcriptomic adaptations in VISA DAP-R CA-MRSA.
  • To understand the mechanisms underlying the emergence of extensive antimicrobial resistance in CA-MRSA.
  • To identify compensatory mechanisms balancing virulence and resistance.

Main Methods:

  • Whole-genome sequencing
  • RNA-Sequencing (RNA-Seq)
  • Bioinformatics analysis
  • Resistomics

Main Results:

  • The CA-MRSA strain belonged to the USA400 lineage and exhibited resistance to daptomycin and glycopeptides.
  • Adaptations included mutations and overexpression of genes related to glycopeptide, daptomycin, and rifampin resistance.
  • Virulence traits showed decreased expression, despite abundant virulence genes, indicating a balance between resistance and virulence.
  • A compensatory modulatory mutation was identified, silencing the Agr quorum-sensing cascade.

Conclusions:

  • VISA DAP-R CA-MRSA exhibits a shift from hypervirulence towards acquiring and maintaining extensive antimicrobial resistance.
  • This shift is mediated by decreased virulence and biological costs.
  • A compensatory mutation silencing the Agr quorum-sensing cascade plays a crucial role in maintaining extensive AMR.
Keywords:
CA-MRSAVISAantimicrobial resistanceomicsvirulence

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