Abstract
The filamentous fungus Lomentospora (Scedosporium) prolificans is an emerging opportunistic pathogen associated with fatal infections in patients with disturbed immune function. Unfortunately, conventional therapies are hardly of any use against this fungus due to its intrinsic resistance. Therefore, we performed an integrated study of the L. prolificans responses to the first option to treat these mycoses, namely voriconazole, with the aim of unveiling mechanisms involved in the resistance to this compound. To do that, we used a wide range of techniques, including fluorescence and electron microscopy to study morphological alterations, ion chromatography to measure changes in cell-wall carbohydrate composition, and proteomics-based techniques to identify the proteins differentially expressed under the presence of the drug. Significantly, we showed drastic changes occurring in cell shape after voriconazole exposure, L. prolificans hyphae being shorter and wider than under control conditions. Interestingly, we proved that the architecture and carbohydrate composition of the cell wall had been modified in the presence of the drug. Specifically, L. prolificans constructed a more complex organelle with a higher presence of glucans and mannans. In addition to this, we identified several differentially expressed proteins, including Srp1 and heat shock protein 70 (Hsp70), as the most overexpressed under voriconazole-induced stress conditions. The mechanisms described in this study, which may be directly related to L. prolificans antifungal resistance or tolerance, could be used as targets to improve existing therapies or to develop new ones in order to successfully eliminate these mycoses.
Highlights
The filamentous fungus Lomentospora prolificans, formerly known as Scedosporium prolificans [1], is an opportunistic pathogen producing mycoses with a wide range of clinical manifestations, from superficial to deep infections
The results show that VRC-treated cells emitted more fluorescence than the controls, this parameter being dependant on the VRC concentration; when the higher concentration was applied it rose to a level that was more than two times higher (Fig 1F)
Ultrastructural and compositional changes on L. prolificans cell wall caused by voriconazole
Summary
The filamentous fungus Lomentospora prolificans, formerly known as Scedosporium prolificans [1], is an opportunistic pathogen producing mycoses with a wide range of clinical manifestations, from superficial to deep infections. When patients suffer from deep immunosuppression, L. prolificans tends to disseminate through the bloodstream due to its capacity. Molecular responses of Lomentospora prolificans to voriconazole design, data collection and analysis, decision to publish, or preparation of the manuscript
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