Rapid Response Antimicrobial Peptide Design Strategy Driven by Meta-Learning for Emerging Drug-Resistant Pathogens

J Med Chem. 2025 Apr 24;68(8):8530-8542. doi: 10.1021/acs.jmedchem.5c00188. Epub 2025 Apr 7.

Abstract

Antimicrobial resistance (AMR) presents a critical global health threat requiring urgent intervention. In order to swiftly respond to and control the spread of emerging drug-resistant bacteria at the onset of their proliferation, our aim is to develop a Rapid Response Antimicrobial Peptide (AMP) design strategy (RR-ADS). This framework addresses the challenge of limited pathogen-specific data by achieving robust generalization from minimal samples by meta-learning and reinforcement learning, optimizing both biocompatibility and efficacy against drug-resistant pathogens. Our model has achieved satisfactory results across multiple evaluation metrics, demonstrating the capability to accurately identify and generate AMPs targeted against drug-resistant bacteria with minimal sample sizes. Within 2 weeks, we successfully designed and experimentally verified AMPs against multidrug-resistant Acinetobacter baumannii, achieving a 93.3% positive rate. RR-ADS has effectively demonstrated the potential of meta-learning in tasks involving bioactive peptides and holds promise as an effective alternative measure to address infectious disease public health emergencies.

MeSH terms

  • Acinetobacter baumannii* / drug effects
  • Anti-Bacterial Agents* / chemical synthesis
  • Anti-Bacterial Agents* / chemistry
  • Anti-Bacterial Agents* / pharmacology
  • Antimicrobial Peptides* / chemical synthesis
  • Antimicrobial Peptides* / chemistry
  • Antimicrobial Peptides* / pharmacology
  • Drug Design*
  • Drug Resistance, Multiple, Bacterial / drug effects
  • Humans
  • Microbial Sensitivity Tests

Substances

  • Antimicrobial Peptides
  • Anti-Bacterial Agents