Efflux pump inhibition controls growth and enhances antifungal susceptibility of Fusarium solani species complex

Future Microbiol. 2020 Jan:15:9-20. doi: 10.2217/fmb-2019-0186. Epub 2020 Feb 11.

Abstract

Aim: To evaluate the inhibition of efflux pumps by using promethazine (PMZ) as a strategy to control Fusarium solani species complex (FSSC). Materials & methods: The susceptibility of FSSC strains to PMZ and the interaction between PMZ and antifungals were evaluated. The efflux pump activity was confirmed by flow cytometry with rhodamine 6G. Finally, PMZ was tested against FSSC biofilms. Results: PMZ inhibited FSSC planktonic growth and showed synergism with antifungals. PMZ reduced R6G efflux and inhibited cell adhesion, impaired the development of biofilms and disrupted mature biofilms. PMZ-challenged biofilms showed increased sensitivity to amphotericin B. Conclusion: The study provides indirect evidence of the occurrence of efflux pumps in FSSC and opens a perspective for this target in the control of fusariosis.

Keywords: Fusarium solani; antifungal resistance; biofilm resistance; biofilms; fungal keratitis; promethazine; synergism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphotericin B / pharmacology
  • Antifungal Agents / pharmacology*
  • Biofilms / drug effects*
  • Drug Resistance, Fungal
  • Drug Synergism
  • Fungal Proteins / antagonists & inhibitors*
  • Fusarium / drug effects*
  • Fusarium / growth & development*
  • Humans
  • Membrane Transport Proteins
  • Microbial Sensitivity Tests
  • Promethazine / pharmacology*
  • Voriconazole / pharmacology

Substances

  • Antifungal Agents
  • Fungal Proteins
  • Membrane Transport Proteins
  • Amphotericin B
  • Promethazine
  • Voriconazole

Supplementary concepts

  • Fusarium solani