Enzymatic synthesis of poly(catechin)-antibiotic conjugates: an antimicrobial approach for indwelling catheters

Appl Microbiol Biotechnol. 2015 Jan;99(2):637-51. doi: 10.1007/s00253-014-6128-2. Epub 2014 Oct 21.

Abstract

Biofilm formation in urinary indwelling catheters is one of the most critical issues that patients face. Catheters were coated with poly(catechin)-antibiotic conjugates with enhanced antimicrobial properties. Catechin was conjugated with two antibiotics, namely trimethoprim (TMP) and sulfamethoxazole (SMZ) via activation with N,N'-disuccinimidyl carbonate (DSC) and subsequent coupling to molecules containing α-amine moieties. Silicone and polyurethane catheters were functionalized in situ through laccase oxidation of catechin-antibiotic conjugates. Four antimicrobial coatings were produced, namely with poly(catechin), poly(catechin)-TMP, poly(catechin)-SMZ and poly(catechin)-TMP-SMZ. The bacterial adhesion reduction was tested on the functionalized devices using gram-negative and gram-positive strains. The most significant reduction in adhesion was observed with poly(catechin)-TMP (gram-negative -85 % and gram-positive -87 %) and with poly(catechin)-TMP-SMZ (gram-negative -85 % and gram-positive -91 %). The cytotoxicity to mammalian cells was tested by indirect contact for 5 days and revealed that all the tested coatings supported more than 90 % of viable cells. A promising approach for the increase of the indwelling catheter lifespan was developed aiming to reduce catheter-associated chronic infections.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Infective Agents / chemical synthesis
  • Anti-Infective Agents / pharmacology*
  • Bacterial Adhesion / drug effects
  • Catechin / chemical synthesis
  • Catechin / pharmacology*
  • Catheters, Indwelling*
  • Cell Line
  • Cell Survival / drug effects
  • Humans
  • Laccase / metabolism
  • Mice
  • Microbial Sensitivity Tests
  • Polyurethanes / chemistry
  • Pseudomonas aeruginosa / drug effects
  • Pseudomonas aeruginosa / growth & development
  • Silicones / chemistry
  • Spectroscopy, Fourier Transform Infrared
  • Sulfamethoxazole / chemistry
  • Sulfamethoxazole / pharmacology
  • Trimethoprim / chemistry
  • Trimethoprim / pharmacology

Substances

  • Anti-Infective Agents
  • Polyurethanes
  • Silicones
  • Catechin
  • Trimethoprim
  • Laccase
  • Sulfamethoxazole