Abstract
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.
Highlights
Cryptococcosis is a potentially fatal fungal infection caused mainly by species of the Cryptococcus gattii and Cryptococcus neoformans complexes (Maziarz and Perfect, 2016)
Minimal inhibitory concentrations (MICs) ≥1,000.0 μg/ml for the plant compounds were detected for most cryptococcal strains, indicating that they were inactive against planktonic cells
C. neoformans CN12 strain was more sensitive to P. pluviosa extracts, judging by the MIC values equal to 1,000.0 and 125.0 μg/ml for crude hydroalcoholic extract (CE) and EAF, respectively
Summary
Cryptococcosis is a potentially fatal fungal infection caused mainly by species of the Cryptococcus gattii and Cryptococcus neoformans complexes (Maziarz and Perfect, 2016). The main contributors to the high mortality associated with cryptococcosis in these countries include delayed diagnosis, limited access and high cost of the drugs used in the induction phase and difficulty in monitoring drug toxicity (WHO, 2018). The etiological treatment of cryptococcosis is of paramount importance to reduce the mortality rate of this disease, and the use of a potent fungicidal agent during the induction (initial) phase is highly recommended (Maziarz and Perfect, 2016; Bermas and Geddes-McAlister, 2020). The etiological treatment of cryptococcosis is based on and limited to the use (alone or combined) of the polyene amphotericin B (AmB), azoles derivatives (mainly fluconazole), and the pyrimidine analog flucytosine, whose treatment regimens depend on the clinical presentation and the immune status of the patient (Perfect et al, 2010; Bermas and Geddes-McAlister, 2020)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
