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Promethazine inhibits efflux, enhances antifungal susceptibility and disrupts biofilm structure and functioning in Trichosporon

Trichosporon spp. are emerging opportunistic fungi associated with invasive infections, especially in patients with haematological malignancies. The present study investigated the in vitro inhibition of efflux pumps by promethazine (PMZ) as a strategy to control T. asahii and T. inkin. Planktonic ce...

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Published in:Biofouling (Chur, Switzerland) Switzerland), 2023-02, Vol.39 (2), p.218-230
Main Authors: Aguiar, Ana Luiza Ribeiro, Silva, Bruno Nascimento da, Fiallos, Nicole de Mello, Pereira, Lívia Maria Galdino, Silva, Maria Laína, Souza, Pedro Freitas Santos Manzi de, Portela, Fernando Victor Monteiro, Sidrim, José Júlio Costa, Rocha, Marcos Fábio Gadelha, Castelo-Branco, Débora Souza Collares Maia, Cordeiro, Rossana de Aguiar
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Language:English
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Summary:Trichosporon spp. are emerging opportunistic fungi associated with invasive infections, especially in patients with haematological malignancies. The present study investigated the in vitro inhibition of efflux pumps by promethazine (PMZ) as a strategy to control T. asahii and T. inkin. Planktonic cells were evaluated for antifungal susceptibility to PMZ, as well as inhibition of efflux. The effect of PMZ was also studied in Trichosporon biofilms. PMZ inhibited T. asahii and T. inkin planktonic cells at concentrations ranging from 32 to 256 μg   ml -1 . Subinhibitory concentrations of PMZ inhibited efflux activity in Trichosporon. Biofilms were completely eradicated by PMZ. PMZ potentiated the action of antifungals, affected the morphology, changed the amount of carbohydrates and proteins and reduced the amount of persister cells inside biofilms. The results showed indirect evidences of the occurrence of efflux pumps in Trichosporon and opens a perspective for the use of this target in the control of trichosporonosis.
ISSN:0892-7014
1029-2454
DOI:10.1080/08927014.2023.2202315