Frontiers in Microbiology (Jun 2021)

Antifungal Combination of Ethyl Acetate Extract of Poincianella pluviosa (DC.) L. P. Queiros Stem Bark With Amphotericin B in Cryptococcus neoformans

  • Gabriella Maria Andriani,
  • Ana Elisa Belotto Morguette,
  • Laís Fernanda Almeida Spoladori,
  • Patrícia Morais Lopes Pereira,
  • Weslei Roberto Correia Cabral,
  • Bruna Terci Fernandes,
  • Eliandro Reis Tavares,
  • Eliandro Reis Tavares,
  • Ricardo Sérgio Almeida,
  • Cesar Armando Contreras Lancheros,
  • Celso Vataru Nakamura,
  • Celso Vataru Nakamura,
  • João Carlos Palazzo Mello,
  • Lucy Megumi Yamauchi,
  • Lucy Megumi Yamauchi,
  • Sueli Fumie Yamada-Ogatta,
  • Sueli Fumie Yamada-Ogatta

DOI
https://doi.org/10.3389/fmicb.2021.660645
Journal volume & issue
Vol. 12

Abstract

Read online

Cryptococcus neoformans is the leading cause of cryptococcosis, an invasive and potentially fatal infectious disease. Therapeutic failures are due to the increase in antifungal resistance, the adverse effects of drugs, and the unavailability of therapeutic regimens in low-income countries, which limit the treatment of cryptococcosis, increasing the morbidity and mortality associated with these infections. Thus, new antifungal drugs and innovative strategies for the cryptococcosis treatment are urgently needed. The aim of the present study was to evaluate the effect of ethyl acetate fraction (EAF) of Poincianella pluviosa stem bark on planktonic and biofilm mode of growth of C. neoformans. Furthermore, the interaction between the EAF and amphotericin B (AmB) was evaluated in vitro and in Galleria mellonella infection model. Minimal inhibitory concentrations (MICs) of EAF ranged from 125.0 to >1,000.0 μg/ml and >1,000.0 μg/ml for planktonic and sessile cells, respectively. The combination between EAF and AmB exhibited a synergistic fungicidal activity toward C. neoformans, with a fractional inhibitory concentration index (FICI) ranging from 0.03 to 0.06 and 0.08 to 0.28 for planktonic and sessile cells, respectively. Microscopy analyses of planktonic C. neoformans cells treated with EAF, alone or combined with AmB, revealed morphological and ultrastructural alterations, including loss of integrity of the cell wall and cell membrane detachment, suggesting leakage of intracellular content, reduction of capsule size, and presence of vacuoles. Moreover, EAF alone or combined with AmB prolonged the survival rate of C. neoformans-infected G. mellonella larvae. These findings indicate that P. pluviosa may be an important source of new compounds that can be used as a fungus-specific adjuvant for the treatment of cryptococcosis.

Keywords