Scedosporium and Pseudallescheria low molecular weight metabolites revealed by database search
Lukáš KrásnýMartin StrohalmJean‐Philippe BoucharaMiroslav ŠulcKarel LemrEliana Barreto‐BergterVladimı́r Havlı́ček
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Abstract:
Summary The potential of mMass software search tool with new compound libraries was demonstrated on metabolomics of Scedosporium prolificans , S. apiospermum and Pseudallescheria boydii sensu stricto . Cyclic peptides pseudacyclins, small molecular weight tyroscherin analogues and various lipids were annotated by public software tool ( http://www.mmass.org ) utilising accurate matrix‐assisted laser desorption/ionisation mass spectral data of intact fungal spores. Electrospray ionisation combined with tandem mass spectrometry was used for monohexosylceramide characterisation in fungal extracts.Keywords:
Scedosporium apiospermum
Scedosporium apiospermum is known to be a fungal pathogen affecting immunocompromised as well as non-immunodeficient patients. Although this fungus is found rarely, an infection can lead to severe and even fatal disease. Here, we describe the case of a 41-year-old female who developed multiple Scedosporium apiospermum brain abscesses after near-drowning with aspiration of contaminated mud and water. She showed various neurological symptoms. The patient recovered after removal of abscesses in combination with long-term antifungal treatment.
Scedosporium apiospermum
Opportunistic pathogen
Brain abscess
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Scedosporium infections are rare complications in immunocompromised patients or patients with chronic pulmonary disease. While Scedosporium prolificans is resistant to most antimycotics, Scedosporium apiospermum is usually sensitive to voriconazole and posaconazole. Pharmacokinetics and efficacyof nebulized voriconazolehavebeendescribedina murinemodelpreviously. We report for the first timethesafeandeffectiveuse of nebulized voriconazole for the treatment of severe pulmonary infection with Scedosporium apiospermum in an adolescent with cystic fribrosis.
Scedosporium apiospermum
Posaconazole
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Summary Scedosporium apiospermum is an emerging fungal pathogen, increasingly recognised as a cause of infection not only in immunocompromised, but also in non‐immunodeficient patients. We present the case of an immunocompetent 21‐year‐old Thai man who experienced recurrent ruptured mycotic aneurysms and developed multiple S. apiospermum brain abscesses following aspiration of polluted water. A combination of surgery and voriconazole was effective in this difficult‐to‐treat case. Voriconazole penetrated the central nervous system (CNS) well and had limited toxicity, despite prolonged treatment. Voriconazole appears to be the antifungal agent of choice in the treatment of CNS scedosporiosis caused by S . apiospermum .
Scedosporium apiospermum
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Scedosporium apiospermum (S. apiospermum) is typically reported to be involved in superficial and subcutaneous fungal infections but overlooked in invasive infections, which is associated with a high mortality rate. It poses a diagnostic challenge due to its confusable characteristics to other hyaline hyphomycetes. Here, we reported a psoriasis patient with an invasive S. apiospermum infection. The patient presents an abscess at the intermuscular space of the left hip and an increased C-reactive protein level. Pus culture showed white-greyish, cottonlike colonies with aerial mycelium and terminal oval conidia, suggesting S. apiospermum. This rare fungus was rapidly confirmed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and RNA sequencing. The patient was successfully treated with voriconazole with no recurrence of the abscesses despite delayed treatment. This is the first such case infection report from China that described an unusual case of intermuscular space abscesses due to S. apiospermum. This report highlights the possibility of fungal infections in deeper tissue, as well as the necessity of thorough evaluation and microbiological diagnosis for invasive infections, particularly in immunocompromised patients.
Scedosporium apiospermum
Fungal Keratitis
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Scedosporium apiospermum (also known as Pseudallescheria boydii) is a ubiquitous filamentous fungus. This fungus is known as a cause of mycetoma, which may occur in a normally immune host following trauma. However, in an immunocompromised host, S. apiospermum may cause a life-threatening infection. We describe a case of S. apiospermum infection of the right hand in a patient who was receiving long-term immunosuppressants for adult Still's disease. We also review the cases of S. apiospermum infection with cutaneous manifestations reported between 1998 and 2003.
Scedosporium apiospermum
Mycetoma
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The presence of the nucleoside antitumor antibiotic toyocamycin in the fermentation broth was determined by a combination of negative and positive ion fast atom bombardment (FAB) mass spectrometry, high resolution FAB mass spectrometry and mass-analysed ion kinetic energy spectrometry (MIKES). A reasonable limit of detection for toyocamycin in the whole broth was obtained by combining the specificity of mass spectrometry/mass spectrometry (also called tandem mass spectrometry) to FAB. The role played by the fermentation matrix upon the production and the observation of characteristic ions by FAB using xenon atoms was examined. High-performance liquid chromatography (HPLC) and FAB mass spectrometry were used to monitor toyocamycin at all stages of strain development, fermentation and recovery.
Fast atom bombardment
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Metabolomics is the study of low molecular weight molecules or metabolites produced within cells and biological systems. It involves technologies such as mass spectrometry (MS) and nuclear magnetic resonance spectroscopy (NMR) that can measure hundreds of thousands of unique chemical entities (UCEs). The metabolome provides one of the most accurate reflections of cellular activity at the functional level and can be leveraged to discern mechanistic information during normal and disease states. The advantages of metabolomics over other “omics” include its high sensitivity and ability to enable the analysis of relatively few metabolites compared with the number of genes and messenger RNAs (mRNAs). In clinical samples, metabolites are more stable than proteins or RNA. In fact, metabolomic profiling in basic, epidemiologic, clinical, and translational studies has revealed potential new biomarkers of disease and therapeutic outcome and has led to a novel mechanistic understanding of pathogenesis. These potential biomarkers include novel metabolites associated with cancer initiation, regression, and recurrence. Unlike genomics or even proteomics, however, the degree of metabolite complexity and heterogeneity within biological systems presents unique challenges that require specialized skills and resources to overcome. This article discusses epidemiologic studies of altered metabolite profiles in several cancers as well as challenges in the field and potential approaches to overcoming them.
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We report the case of a 42-year-old man with a 13-year history of bilateral faciocervical infiltrative erythema, which had been misdiagnosed as tuberculoderma and which had failed to respond to treatment with adrenal corticosteroids and antituberculotics. On admission to the department, Scedosporium apiospermum was identified on lesion biopsies and fungus cultures as the causative agent and a diagnosis of cutaneous infection by S. apiospermum was made. This is the first report of chronic skin granuloma caused by S. apiospermum in China. Treatment with oral itraconazole (100-400 mg/day) led to clinical cure within 4 months.
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Terbinafine
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Scedosporium apiospermum infection occurred in the left forearm of a patient who was taking oral prednisolone for pulmonary fibrosis. The infection appeared to follow a scratch from a blackcurrant bush. This is the first reported case in the United Kingdom of a cutaneous infection from Scedosporium apiospermum in an immunocompromised patient.
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Tandem mass spectrometry has become a powerful tool for basic and applied mass spectrometry studies. Mass spectrometers based on ion trapping techniques, such as the quadrupole ion trap, have some unique capabilities as tandem mass spectrometers. Of particular note are the high MS–MS efficiency, the ability to perform multiple stages of tandem spectrometry (MSn), and the ability to effect ion–molecule reactions as part of the experimental sequence. This paper discusses the MSn experiment in a quadrupole ion trap and provides several examples of MSn experiments in which ion–molecule reactions are incorporated as one or more steps in the experiment. Examples include one in which MSn is used to determine the structure of an ion–molecule reaction product, one that involves multiple stages of collision-induced dissociation to generate a 13C containing reactant ion for an isotopic study, and one in which ion–molecule reactions are used to differentiate isomeric ion structures.
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