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

Ana Luiza Ribeiro AguiarBruno Nascimento da SilvaNicole de Mello FiallosLívia Maria Galdino PereiraMaria Laína SilvaPedro Freitas Santos Manzi de SouzaFernando Victor Monteiro PortelaJosé Júlio da Costa SidrimMarcos Fábio Gadelha RochaDébora de Souza Collares Maia Castelo-BrancoRossana de Aguiar Cordeiro
Published in: Biofouling (2023)
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.
Keyphrases
  • candida albicans
  • induced apoptosis
  • cell cycle arrest
  • risk assessment
  • cell death
  • biofilm formation
  • high resolution
  • staphylococcus aureus
  • cell proliferation