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

• Published in: Future microbiology Vol. 15; no. 1; pp. 9 - 20
• Main Authors: A Cordeiro, Rossana de, Portela, Fernando Vm, Pereira, Lívia Mg, de Andrade, Ana Rc, de Sousa, José K, Aguiar, Ana Lr, Pergentino, Mariana Lm, de Sales, Gyrliane S, de Oliveira, Jonathas S, Medrano, Delia Ja, Brilhante, Raimunda Sn, Rocha, Marcos Fg, Scm Castelo-Branco, Débora de, Sidrim, José Jc
• Format: Journal Article
• Language: English
• Published: England Future Medicine Ltd 01.01.2020
• Subjects: Amphotericin B; Amphotericin B - pharmacology; Antifungal agents; Antifungal Agents - pharmacology; Biofilms; Biofilms - drug effects; Cell adhesion; Cell adhesion & migration; Drug Resistance, Fungal; Drug Synergism; Flow cytometry; Fungal Proteins - antagonists & inhibitors; Fungi; Fusariosis; Fusarium - drug effects; Fusarium - growth & development; Fusarium solani; Glucose; Humans; Membrane Transport Proteins; Microbial Sensitivity Tests; Promethazine; Promethazine - pharmacology; Rhodamine 6G; Voriconazole - pharmacology; Brazil; United States > US; biofilm resistance; promethazine; fungal keratitis; synergism; Fusarium solani; biofilms; antifungal resistance
• ISSN: 1746-0913; 1746-0921
• DOI: 10.2217/fmb-2019-0186

To evaluate the inhibition of efflux pumps by using promethazine (PMZ) as a strategy to control species complex (FSSC). 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. 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. 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.