Fungal strains and the development of tolerance against natamycin

• Nineteen fungal species were tested for the development of antimicrobial tolerance for natamycin.
• The range of M.I.C. did not change; the average M.I.C. increased.
• Four strains showed a > 2-fold increase of tolerance.
• One strain also had developed increased tolerance to amphotericin B and nystatin.

Antimicrobial resistance is a relevant theme with respect to both antibacterial and antifungal compounds. In this study we address the possible development of tolerance against the antifungal food preservative natamycin. A selection of 20 fungal species, originating from a medical as well as a food product context, was subjected to increasing concentrations of natamycin for prolonged time, a procedure designated as “training”. The range of Minimum Inhibitory Concentrations (M.I.C.) before (1.8–19.2 μM) and after (1.8–19.8 μM) training did not change significantly, but natamycin-exposure caused an increase of M.I.C. in 13 out of 20 tested strains. The average M.I.C. increased from 6.1 to 8.6 μM and 4 strains showed a > 2-fold increase of tolerance after training. One strain (of Aspergillus ochraceus) also showed increased tolerance to amphotericin B and nystatin. However, two Fusarium strains showed similar or even decreased tolerance for these other polyene antifungals.The work reported here shows that a continuous and prolonged increasing selection pressure induced natamycin tolerance in individual strains. This implies that such a selection pressure should be avoided in the technical application of natamycin to ensure its continued safe use as a food preservative.