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Structural and Functional Alterations Caused by Aureobasidin A in Clinical Resistant Strains of Candida spp

Rodrigo Rollin-Pinheiro1, Daniel Clemente de Moraes2, Brayan Bayona-Pacheco2,3

  • 1Laboratório de Química Biológica de Microrganismos, Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, Brazil.

Journal of Fungi (Basel, Switzerland)
|November 24, 2023
PubMed

Insights

Aureobasidin A shows promise in combating resistant Candida fungal infections. When combined with fluconazole, it effectively targets Candida biofilms and protects against infection in animal models.

Area of Science:

  • Mycology
  • Infectious Diseases
  • Pharmacology

Background:

  • Invasive fungal infections caused by Candida species are a significant global health concern.
  • Fluconazole resistance in Candida isolates necessitates the exploration of alternative antifungal agents.
  • Sphingolipid biosynthesis is a validated target for antifungal drug development.

Purpose of the Study:

  • To investigate the efficacy of aureobasidin A, a sphingolipid biosynthesis inhibitor, against Candida biofilms and invasive infections.
  • To evaluate the synergistic potential of aureobasidin A in combination with existing antifungal drugs.
  • To elucidate the cellular mechanisms underlying aureobasidin A's antifungal activity.

Main Methods:

  • Antifungal susceptibility testing against Candida biofilms.
  • In vivo efficacy studies in a murine infection model.
  • Analysis of cellular damage markers including oxidative stress, membrane potential, and DNA leakage.
  • Investigation of efflux pump inhibition and cell wall integrity.

Main Results:

  • Aureobasidin A alone lacked antibiofilm activity and did not synergize with amphotericin B.
  • The combination of aureobasidin A and fluconazole demonstrated significant antibiofilm efficacy and in vivo protection.
  • Cellular analysis revealed increased oxidative stress, reduced mitochondrial potential, and impaired cell wall integrity in treated Candida.
  • Aureobasidin A appeared to inhibit the CaCdr2p efflux pump and increase susceptibility to SDS.

Conclusions:

  • Aureobasidin A, particularly in combination with fluconazole, represents a promising therapeutic strategy against fluconazole-resistant Candida biofilms and infections.
  • The drug induces significant cellular stress and compromises cell integrity in Candida species.
  • Further research into aureobasidin A holds potential for clinical applications against challenging Candida infections.
Keywords:
Candidaaureobasidin Afungal infectionmembranesphingolipids

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