Biochemical and structural studies of target lectin SapL1 from the emerging opportunistic microfungus Scedosporium apiospermum

Scedosporium apiospermum is an emerging opportunistic fungal pathogen responsible for life-threatening infections in humans. Host–pathogen interactions often implicate lectins that have become therapeutic targets for the development of carbohydrate mimics for antiadhesive therapy. Here, we present the first report on the identification and characterization of a lectin from S. apiospermum named SapL1. SapL1 was found using bioinformatics as a homolog to the conidial surface lectin FleA from Aspergillus fumigatus known to play a role in the adhesion to host glycoconjugates present in human lung epithelium. In our strategy to obtain recombinant SapL1, we discovered the importance of osmolytes to achieve its expression in soluble form in bacteria. Analysis of glycan arrays indicates specificity for fucosylated oligosaccharides as expected. Submicromolar affinity was measured for fucose using isothermal titration calorimetry. We solved SapL1 crystal structure in complex with α-methyl-L-fucoside and analyzed its structural basis for fucose binding. We finally demonstrated that SapL1 binds to bronchial epithelial cells in a fucose-dependent manner. The information gathered here will contribute to the design and development of glycodrugs targeting SapL1.

Scedosporium apiospermum contact lens-related keratitis: A rare case report and a literature review

Background: Scedosporium apiospermum (SA) is commonly present in temperate climates. It can induce cutaneous and subcutaneous tissue infections as well as disseminated infections in immunocompromised or immunocompetent hosts. The eye is rarely involved. Keratomycosis is usually caused by plant-related injuries. Here, we describe a patient with a severe and sight-threatening corneal abscess caused by SA, which was associated with contact lens wear and was successfully treated with a combination of surgical and medical therapies. Case Presentation: An otherwise healthy 22-year-old woman, with history of contact lens wearing, was referred to the Ophthalmic Department of Bari University, Bari, Italy for evaluation of a corneal abscess and hypopyon in her left eye. Intensive topical and systemic antibiotic therapy was initiated after obtaining conjunctival swabs. Within 2 days, her ophthalmic condition had worsened, and her best-corrected visual acuity (BCVA) dropped to counting fingers. She underwent penetrating keratoplasty, after which her ophthalmic condition improved. Microbiological culture, obtained from the explanted cornea, revealed SA infection. This was addressed with specific topical and systemic therapy using voriconazole. Two weeks later, the condition of her left eye was stable, with mild corneal edema and no sign of acute graft rejection. Her BCVA improved to 20/25, and all medications were discontinued, except for the steroid eye drop. The patient was scheduled for a 1-month follow-up. Conclusions: Prompt identification of the etiological agent is mandatory to perform appropriate therapy in cases of keratomycosis. Surgery to remove the infected cornea is helpful in patients with deteriorating condition, in whom the initial medical therapy has failed. Topical and systemic antimycotic therapy, based on microbiological culture, is recommended as an adjunctive therapy for the surgical management of severe corneal mycotic abscesses. How to cite this article: Cassano F, Cardascia N, Tegola MGL, Boscia F, Alessio G. Scedosporium apiospermum contact lens-related keratitis: A rare case report and a literature review. Med Hypothesis Discov Innov Ophthalmol. 2021 Summer, 10(2): 80-85 https://doi.org/10.51329/mehdiophthal1425

In vivo efficacy of olorofim against systemic scedosporiosis and lomentosporiosis

Clinically relevant members of the Scedosporium / Pseudallescheria species complex and Lomentospora prolificans are generally resistant against currently available systemic antifungal agents in vitro and the infection due to these species is difficult to treat. We studied the in vivo efficacy of a new fungicidal agent olorofim (formerly F901318) against scedosporiosis and lomentosporiosis in neutropenic animals. Cyclophosphamide immunosuppressed CD-1 mice infected by Scedosporium apiospermum , Pseudallescheria boydii ( Scedosporium boydii ) and Lomentospora prolificans were treated by intraperitoneal administration of olorofim (15 mg/kg every 8 h for 9 days). The efficacy of olorofim treatment was assessed by the survival rate at 10 days post infection, levels of serum (1-3)-β-d-glucan (BG), histopathology, and fungal burden of kidneys 3 days post infection. Olorofim therapy significantly improved survival compared to the untreated controls; 80%, 100% and 100% of treated mice survived infection by Scedosporium apiospermum , Pseudallescheria boydii , and Lomentospora prolificans, respectively while less than 20% of the control mice (PBS-treated) survived at 10 days post infection. In the olorofim-treated neutropenic CD-1 mice infected with all three species, serum BG levels were significantly suppressed and fungal DNA detected in the target organs was significantly lower than controls. Furthermore, histopathology of kidneys revealed no or only few lesions with hyphal elements in the olorofim-treated mice, while numerous fungal hyphae were present in control mice. These results indicate olorofim to be a promising therapeutic agent for systemic scedosporiosis/lomentosporiosis, a devastating emerging fungal infection difficult to treat with currently available antifungals.

Post COVID-19 acute invasive fungal rhinosinusitis caused by Scedosporium apiospermum: a covert pathogen

<p class="abstract">Immune dysregulation caused by COVID-19 and the presence of risk factors such as diabetes, steroid therapy and immune-modulatory drugs significantly increase the risk of secondary invasive fungal infections. <em>Scedosporium apiospermum </em>is an emerging pathogen and is rarely reported as a cause of fungal rhinosinusitis. This was a previously unreported case of post COVID-19 acute invasive fungal rhinosinusitis caused by <em>S. apiospermum</em> with rare complications of cranial nerve palsies and ruptured mycotic intracranial aneurysm.</p>