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Mucin Binding Reduces Colistin Antimicrobial Activity.

Johnny X Huang1, Mark A T Blaskovich1, Ruby Pelingon1

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Colistin and other positively charged antibiotics bind to airway mucins, reducing their effectiveness against lung infections. This mucin binding may lower drug levels and promote antibiotic resistance.

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Area of Science:

  • Pharmacology
  • Microbiology
  • Biochemistry

Background:

  • Colistin is increasingly used for drug-resistant bacterial lung infections.
  • Potential interactions between colistin and pulmonary biomolecules remain unexplored.
  • Aminoglycoside antibiotics are known to bind to mucins, affecting drug levels.

Purpose of the Study:

  • To investigate the binding of colistin and other antibiotics to mucins.
  • To determine if mucin binding affects antibiotic efficacy in treating lung infections.
  • To assess the implications of mucin binding for antibiotic resistance.

Main Methods:

  • Porcine mucin was used as a surrogate for human sputum and airway mucin.
  • Antibiotics were incubated with or without mucin in dialysis tubing.
  • Unbound antibiotic concentrations were measured over time using liquid chromatography-tandem mass spectrometry (LC-MS/MS).
  • Minimum Inhibitory Concentrations (MICs) were compared with and without added mucin.

Main Results:

  • Colistin, polymyxin B, and tobramycin showed significant binding to mucin.
  • Antibiotics with a polybasic positive charge exhibited stronger mucin binding.
  • Colistin and polymyxin B demonstrated over 100-fold increases in MICs in the presence of mucin.
  • Mcin binding reduced free drug levels, potentially leading to sub-inhibitory concentrations.

Conclusions:

  • Colistin and other positively charged antibiotics can bind to airway mucins.
  • This binding reduces effective drug concentrations, potentially compromising treatment of lung infections.
  • Preclinical evaluation of mucin binding is recommended for pulmonary antibiotics.
  • Mcin binding may contribute to the development of antibiotic resistance.