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Unseen Enemy: Mechanisms of Multidrug Antimicrobial Resistance in Gram-Negative ESKAPE Pathogens

Giedrė Valdonė Sakalauskienė1, Lina Malcienė1, Edgaras Stankevičius1

  • 1Institute of Physiology and Pharmacology, Faculty of Medicine, Medical Academy, Lithuanian University of Health Sciences, 44307 Kaunas, Lithuania.

Antibiotics (Basel, Switzerland)
|January 25, 2025
PubMed

Insights

Multidrug antimicrobial resistance (AMR) in gram-negative ESKAPE pathogens is a major global health threat. Understanding resistance mechanisms like drug efflux and target modification is crucial for developing new treatments.

Area of Science:

  • Microbiology
  • Infectious Diseases
  • Pharmacology

Background:

  • Multidrug antimicrobial resistance (AMR) poses a significant challenge in treating infections, especially from gram-negative ESKAPE pathogens.
  • ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp.) are a priority due to rising resistance.
  • The COVID-19 pandemic exacerbated the threat, with coinfections leading to poorer patient outcomes and increased mortality.

Purpose of the Study:

  • To review the sophisticated mechanisms driving AMR in gram-negative ESKAPE bacteria.
  • To focus on Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Enterobacter spp.
  • To highlight the importance of understanding these mechanisms for developing new therapies.

Main Methods:

  • Literature review of scientific articles and reports on antimicrobial resistance in ESKAPE pathogens.
  • Analysis of key bacterial resistance mechanisms.
  • Synthesis of information on drug uptake, enzyme degradation, target modification, and efflux systems.

Main Results:

  • Gram-negative ESKAPE bacteria employ diverse strategies to resist antibiotics.
  • Mechanisms include reduced drug permeability, antibiotic-inactivating enzymes, altered drug targets, and active efflux pumps.
  • These mechanisms contribute to the declining effectiveness of current treatments.

Conclusions:

  • A comprehensive understanding of AMR mechanisms in gram-negative ESKAPE pathogens is essential.
  • This knowledge is vital for designing novel therapeutic strategies.
  • Addressing AMR in these priority pathogens is critical to reduce the global disease burden and mortality.
Keywords:
antimicrobial resistancemechanisms of antimicrobial resistancemultidrug-resistant gram-negative ESKAPE pathogens

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