Abstract
Scedosporium and Lomentospora species are filamentous fungi responsible for a wide range of infections in humans and are frequently associated with cystic fibrosis and immunocompromising conditions. Because they are usually resistant to many antifungal drugs available in clinical settings, studies of alternative targets in fungal cells and therapeutic approaches are necessary. In the present work, we evaluated the in vitro antifungal activity of miltefosine against Scedosporium and Lomentospora species and how this phospholipid analogue affects the fungal cell. Miltefosine inhibited different Scedosporium and Lomentospora species at 2–4 µg/ml and reduced biofilm formation. The loss of membrane integrity in Scedosporium aurantiacum caused by miltefosine was demonstrated by leakage of intracellular components and lipid raft disorganisation. The exogenous addition of glucosylceramide decreased the inhibitory activity of miltefosine. Reactive oxygen species production and mitochondrial activity were also affected by miltefosine, as well as the susceptibility to fluconazole, caspofungin and myoricin. The data obtained in the present study contribute to clarify the dynamics of the interaction between miltefosine and Scedosporium and Lomentospora cells, highlighting its potential use as new antifungal drug in the future.
Highlights
Scedosporium and Lomentospora species are ubiquitous filamentous fungi known to be emergent pathogens that cause localised to disseminated infections with a broad range of clinical manifestations
The minimum inhibitory concentration (MIC) observed for S. aurantiacum, S. apiospermum, S. dehoogii and L. prolificans was 4 mg/ml, whereas for S. boydii it was 2 mg/ml (Table 1)
Scedosporium and Lomentospora species are considered the second most frequent fungi associated with pulmonary colonisation in cystic fibrosis patients (Schwarz et al, 2017; Engel et al, 2019)
Summary
Scedosporium and Lomentospora species are ubiquitous filamentous fungi known to be emergent pathogens that cause localised to disseminated infections with a broad range of clinical manifestations. Immunocompromised individuals, such as organ transplant recipients, HIV/ AIDS patients and cystic fibrosis patients, are at greater risk of developing invasive infections with high mortality rates (Cortez et al, 2008; Luplertlop, 2018; Engel et al, 2019). S. aurantiacum induced 80% mortality in immunocompetent mice, an effect that could be correlated to its capacity to germinate rapidly, to resist oxidative stress and to form robust biofilm on various types of surfaces, such as central venous catheters and cell cultures (Gilgado et al, 2009; Mello et al, 2016; Rollin-Pinheiro et al, 2017; Staerck et al, 2018)
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