Connecting membrane fluidity and surface charge to pore-forming antimicrobial peptides resistance by an ANN-based

Jitender Mehla1, S K Sood

  • 1Animal Biochemistry Division, National Dairy Research Institute, Karnal 132001 Haryana, India. jitendermehla@gmail.com

Insights

Antibiotic resistance is a growing threat. This study uses artificial neural networks (ANNs) to model how pore-forming antimicrobial peptides (PF-AMPs) interact with bacterial membranes, offering insights into overcoming resistance.

Area of Science:

  • Biochemistry
  • Computational Biology
  • Drug Discovery

Background:

  • Antibiotic resistance poses a significant global health challenge.
  • Pore-forming antimicrobial peptides (PF-AMPs) are a promising alternative to conventional antibiotics.
  • Understanding PF-AMP interactions with bacterial membranes is crucial for developing new therapies.

Purpose of the Study:

  • To develop an artificial neural network (ANN)-based quantitative structure-activity relationship (SAR) model for PF-AMPs and membrane phospholipids.
  • To investigate the influence of membrane fluidity and surface charge on PF-AMP activity and bacterial resistance.
  • To establish a predictive model for PF-AMP efficacy against resistant bacterial strains.

Main Methods:

  • Utilized an artificial neural network (ANN) for quantitative structure-activity relationship (SAR) modeling.
  • Analyzed the interaction of PF-AMPs, specifically alamethicin (Alm), with various membrane phospholipids.
  • Correlated bacterial resistance with membrane fluidity and surface charge characteristics.

Main Results:

  • PF-AMP potency is significantly influenced by the fatty acyl chain and polar head group of phospholipids.
  • Alamethicin interacts differently with zwitterionic and anionic membranes, showing deeper penetration into anionic lipid bilayers.
  • A strong correlation (R=0.757) was observed between predicted and observed bacterial resistance using the ANN model.
  • The study provides a novel method for predicting and quantifying PF-AMP interactions with membrane phospholipids.

Conclusions:

  • ANNs provide a reliable method for predicting bacterial resistance based on membrane properties.
  • Understanding membrane-PF-AMP interactions is key to designing effective antimicrobial peptides.
  • This research offers a framework for developing novel PF-AMPs to combat antibiotic resistance.

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