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Putative role of an ABC transporter in Fonsecaea pedrosoi multidrug resistance

Luciana P Rangel1, Otacílio C Moreira, Gustavo N Livramento

  • 1Departamento de Microbiologia Geral, Laboratório de Bioquímica Microbiana/IMPPG, CCS, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho 373, Cidade Universitária, CEP 21941902, Rio de Janeiro, Brazil.

International Journal of Antimicrobial Agents
|September 25, 2012
PubMed

Insights

This study characterizes an ATP-binding cassette (ABC) transporter in Fonsecaea pedrosoi, linking its expression to drug resistance in chromoblastomycosis treatment. Understanding this transporter is crucial for developing new antifungal therapies.

Area of Science:

  • Medical Mycology
  • Molecular Biology
  • Biochemistry

Background:

  • Chromoblastomycosis, caused by Fonsecaea pedrosoi, is a chronic fungal infection characterized by skin and subcutaneous lesions.
  • Treatment is challenging due to antifungal drug toxicity and emerging resistance.
  • ATP-binding cassette (ABC) transporters are implicated in multidrug resistance across various organisms.

Purpose of the Study:

  • To characterize an ATP-binding cassette (ABC) transporter in Fonsecaea pedrosoi.
  • To investigate the relationship between ABC transporter expression and drug resistance in F. pedrosoi.
  • To explore the potential of this transporter as a target for novel antifungal strategies.

Main Methods:

  • Western blotting to detect a 150 kDa protein.
  • ATPase activity assays on membrane preparations.
  • Reverse transcription polymerase chain reaction (RT-PCR) to detect the ATP-binding domain.

Main Results:

  • A 150 kDa protein, likely an ABC transporter, was detected.
  • The transporter exhibited ATPase activity and responded to classical inhibitors, similar to Saccharomyces cerevisiae Pdr5p.
  • RT-PCR confirmed the presence of a conserved ATP-binding domain (400 bp product).
  • Higher expression of the ABC transporter correlated with increased drug resistance in F. pedrosoi strains.

Conclusions:

  • An ABC transporter is involved in Fonsecaea pedrosoi multidrug resistance.
  • Characterization of this ABC transporter provides insights into fungal drug resistance mechanisms.
  • Further understanding of this protein could significantly contribute to improving antifungal treatments for chromoblastomycosis.

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