Antibiotic saving effect of combination therapy through synergistic interactions between well-characterized chito-oligosaccharides and commercial antifungals against medically relevant yeasts

PLoS One. 2019 Dec 31;14(12):e0227098. doi: 10.1371/journal.pone.0227098. eCollection 2019.

Abstract

Combination therapies can be a help to overcome resistance to current antifungals in humans. The combined activity of commercial antifungals and soluble and well-defined low molecular weight chitosan with average degrees of polymerization (DPn) of 17-62 (abbreviated C17 -C62) and fraction of acetylation (FA) of 0.15 against medically relevant yeast strains was studied. The minimal inhibitory concentration (MIC) of C32 varied greatly among strains, ranging from > 5000 μg mL-1 (Candida albicans and C. glabrata) to < 4.9 (C. tropicalis). A synergistic effect was observed between C32 and the different antifungals tested for most of the strains. Testing of several CHOS preparations indicated that the highest synergistic effects are obtained for fractions with a DPn in the 30-50 range. Pre-exposure to C32 enhanced the antifungal effect of fluconazole and amphotericin B. A concentration-dependent post-antifungal effect conserved even 24 h after C32 removal was observed. The combination of C32 and commercial antifungals together or as part of a sequential therapy opens new therapeutic perspectives for treating yeast infections in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphotericin B / pharmacology
  • Amphotericin B / therapeutic use
  • Antifungal Agents / pharmacology*
  • Antifungal Agents / therapeutic use
  • Candida / drug effects*
  • Candida / isolation & purification
  • Candidiasis / drug therapy*
  • Candidiasis / microbiology
  • Chitosan / chemistry
  • Chitosan / pharmacology*
  • Chitosan / therapeutic use
  • Drug Resistance, Fungal / drug effects*
  • Drug Synergism
  • Drug Therapy, Combination
  • Fluconazole / pharmacology
  • Fluconazole / therapeutic use
  • Humans
  • Microbial Sensitivity Tests
  • Polymerization
  • Proton Magnetic Resonance Spectroscopy

Substances

  • Antifungal Agents
  • Amphotericin B
  • Fluconazole
  • Chitosan

Grants and funding

This work was supported by the Norwegian Research Council, 226280 (www.nfr.no) to MG, SBL, BBA, VGHE, PG, and MS. The funding agency din not play any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.