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Fernando L. Hernando - One of the best experts on this subject based on the ideXlab platform.
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Study of Humoral Responses against Lomentospora/Scedosporium spp. and Aspergillus fumigatus to Identify L. prolificans Antigens of Interest for Diagnosis and Treatment.
Vaccines, 2019Co-Authors: Idoia Buldain, Aize Pellon, Aitziber Antoran, Aitor Rementeria, Leire Martin-souto, Beñat Zaldibar, Leire Aparicio-fernandez, Maialen Areitio, Emilio Mayayo, Fernando L. HernandoAbstract:The high mortality rates of Lomentospora prolificans infections are due, above all, to the tendency of the fungus to infect weakened hosts, late diagnosis and a lack of effective therapeutic treatments. To identify proteins of significance for diagnosis, therapy or prophylaxis, immunoproteomics-based studies are especially important. Consequently, in this study murine disseminated infections were carried out using L. prolificans, Scedosporium aurantiacum, Scedosporium boydii and Aspergillus fumigatus, and their sera used to identify the most immunoreactive proteins of L. prolificans total extract and secreted proteins. The results showed that L. prolificans was the most virulent species and its infections were characterized by a high fungal load in several organs, including the brain. The proteomics study showed a high cross-reactivity between Scedosporium/Lomentospora species, but not with A. fumigatus. Among the antigens identified were, proteasomal ubiquitin receptor, carboxypeptidase, Vps28, HAD-like hydrolase, GH16, cerato-platanin and a protein of unknown function that showed no or low homology with humans. Finally, Hsp70 deserves a special mention as it was the main antigen recognized by Scedosporium/Lomentospora species in both secretome and total extract. In conclusion, this study identifies antigens of L. prolificans that can be considered as potential candidates for use in diagnosis and as therapeutic targets and the production of vaccines.
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study of humoral responses against Lomentospora scedosporium spp and aspergillus fumigatus to identify l prolificans antigens of interest for diagnosis and treatment
Vaccine, 2019Co-Authors: Idoia Buldain, Aize Pellon, Aitziber Antoran, Aitor Rementeria, Beñat Zaldibar, Maialen Areitio, Emilio Mayayo, Leire Martinsouto, Leire Apariciofernandez, Fernando L. HernandoAbstract:The high mortality rates of Lomentospora prolificans infections are due, above all, to the tendency of the fungus to infect weakened hosts, late diagnosis and a lack of effective therapeutic treatments. To identify proteins of significance for diagnosis, therapy or prophylaxis, immunoproteomics-based studies are especially important. Consequently, in this study murine disseminated infections were carried out using L. prolificans, Scedosporium aurantiacum, Scedosporium boydii and Aspergillus fumigatus, and their sera used to identify the most immunoreactive proteins of L. prolificans total extract and secreted proteins. The results showed that L. prolificans was the most virulent species and its infections were characterized by a high fungal load in several organs, including the brain. The proteomics study showed a high cross-reactivity between Scedosporium/Lomentospora species, but not with A. fumigatus. Among the antigens identified were, proteasomal ubiquitin receptor, carboxypeptidase, Vps28, HAD-like hydrolase, GH16, cerato-platanin and a protein of unknown function that showed no or low homology with humans. Finally, Hsp70 deserves a special mention as it was the main antigen recognized by Scedosporium/Lomentospora species in both secretome and total extract. In conclusion, this study identifies antigens of L. prolificans that can be considered as potential candidates for use in diagnosis and as therapeutic targets and the production of vaccines.
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Microglial immune response is impaired against the neurotropic fungus Lomentospora prolificans.
Cellular Microbiology, 2018Co-Authors: Aize Pellon, Andoni Ramirez-garcia, Idoia Buldain, Aitziber Antoran, Aitor Rementeria, Xabier Guruceaga, Alazne Zabala, Juan Anguita, Carlos Matute, Fernando L. HernandoAbstract:Lomentospora (Scedosporium) prolificans is an opportunistic pathogen capable of causing invasive infections in immunocompromised patients. The fungus is able to disseminate via the bloodstream finally arriving at the central nervous system producing neurological symptoms and, in many cases, patient death. In this context, microglial cells, which are the resident immune cells in the central nervous system, may play an important role in these infections. However, this aspect of anti-L. prolificans immunity has been poorly researched to date. Thus, the interactions and activity of microglial cells against L. prolificans were analysed, and the results show that there was a remarkable impairment in their performance regarding phagocytosis, the development of oxidative burst, and in the production of pro-inflammatory cytokines, compared with macrophages. Interestingly, L. prolificans displays great growth also when challenged with immune cells, even when inside them. We also proved that microglial phagocytosis of the fungus is highly dependent on mannose receptor and especially on dectin-1. Taken together, these data provide evidence for an impaired microglial response against L. prolificans and contribute to understanding the pathobiology of its neurotropism.
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Pathobiology of Lomentospora prolificans: could this species serve as a model of primary antifungal resistance?
International Journal of Antimicrobial Agents, 2018Co-Authors: Aize Pellon, Andoni Ramirez-garcia, Idoia Buldain, Aitziber Antoran, Aitor Rementeria, Leire Martin-souto, Fernando L. HernandoAbstract:The number of fungal isolates resistant to antifungal drugs has increased dramatically over the last few years and has become an important concern for clinicians. Among these isolates, fungi showing multidrug resistance are particularly worrying because of the difficulties associated with their treatment. These factors hamper the successful recovery of patients and drastically raise mortality rates. Antifungal resistance is multifactorial and several mechanisms in different fungi have been described. There is a need to study these mechanisms in depth; however, the study of antifungal drug resistance separately for each individual species makes progress in the field very slow and tedious. The selection of a multiresistant microorganism as a model for understanding resistance mechanisms and extrapolating the results to other species could help in the search for a solution. In this mini-review, we describe the pathobiology of Lomentospora (Scedosporium) prolificans, paying special attention to its intrinsic resistance to all currently available antifungal agents. The characteristics of L. prolificans offer several advantages: the possibility of using a single microorganism for the study of resistance to different drugs, even cases of double and triple resistance; it is biologically safe for society in general as no new genetically-modified strains are needed for the experiments; it is homologous with other fungal species, and there is repetitiveness between different strains. In conclusion, we propose L. prolificans as a candidate for consideration as a fungal model for the study of resistance mechanisms against antifungal agents.
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Molecular and cellular responses of the pathogenic fungus Lomentospora prolificans to the antifungal drug voriconazole.
PLOS ONE, 2017Co-Authors: Aize Pellon, Andoni Ramirez-garcia, Idoia Buldain, Aitziber Antoran, Aitor Rementeria, Fernando L. HernandoAbstract: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.
Blandine Rammaert - One of the best experts on this subject based on the ideXlab platform.
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perspectives on scedosporium species and Lomentospora prolificans in lung transplantation results of an international practice survey from escmid fungal infection study group and study group for infections in compromised hosts and european confederat
Transplant Infectious Disease, 2019Co-Authors: Blandine Rammaert, Danila Seidel, Oliver A. Cornely, M Puyade, P Grossi, Shahid Husain, C Picard, Cornelia Lassflorl, Oriol ManuelAbstract:BACKGROUND Scedosporium species and Lomentospora prolificans (S/L) are the second most common causes of invasive mold infections following Aspergillus in lung transplant recipients. METHODS We assessed the current practices on management of S/L colonization/infection of the lower respiratory tract before and after lung transplantation in a large number of lung transplant centers through an international practice survey from October 2016 to March 2017. RESULTS A total of 51 respondents from 45 lung transplant centers (17 countries, 4 continents) answered the survey (response rate 58%). S/L colonization was estimated to be detected in candidates by 48% of centers. Only 18% of the centers used a specific medium to detect S/L colonization. Scedosporium spp. colonization was a contraindication to transplantation in 10% of centers whereas L prolificans was a contraindication in 31%; 22% of centers declared having had 1-5 recipients infected with S/L in the past 5 years. CONCLUSIONS This survey gives an overview of the current practices regarding S/L colonization and infection in lung transplant centers worldwide and underscores the need of S/L culture procedure standardization before implementing prospective studies.
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Osteoarticular Infections Caused by Non-Aspergillus Filamentous Fungi in Adult and Pediatric Patients: A Systematic Review.
Medicine, 2016Co-Authors: Saad J. Taj-aldeen, Dimitrios P. Kontoyiannis, Blandine Rammaert, Maria N. Gamaletsou, Nikolaos V. Sipsas, Valérie Zeller, Emmanuel Roilides, Andy O. Miller, Vidmantas Petraitis, Thomas J. WalshAbstract:Osteoarticular mycoses due to non-Aspergillus moulds are uncommon and challenging infections. A systematic literature review of non-Aspergillus osteoarticular mycoses was performed using PUBMED and EMBASE databases from 1970 to 2013. Among 145 patients were 111 adults (median age 48.5 [16–92 y]) and 34 pediatric patients (median age 7.5 [3–15 y]); 114 (79.7%) were male and 88 (61.9%) were immunocompromised. Osteomyelitis was due to direct inoculation in 54.5%. Trauma and puncture wounds were more frequent in children (73.5% vs 43.5%; P = 0.001). Prior surgery was more frequent in adults (27.7% vs 5.9%; P = 0.025). Vertebral (23.2%) and craniofacial osteomyelitis (13.1%) with neurological deficits predominated in adults. Lower limb osteomyelitis (47.7%) and knee arthritis (67.8%) were predominantly seen in children. Hyalohyphomycosis represented 64.8% of documented infections with Scedosporium apiospermum (33.1%) and Lomentospora prolificans (15.8%) as the most common causes. Combined antifungal therapy and surgery was used in 69% of cases with overall response in 85.8%. Median duration of therapy was 115 days (range 5–730). When voriconazole was used as single agent for treatment of hyalohyphomycosis and phaeohyphomycosis, an overall response rate was achieved in 94.1% of cases. Non-Aspergillus osteoarticular mycoses occur most frequently in children after injury and in adults after surgery. Accurate early diagnosis and long-course therapy (median 6 mo) with a combined medical-surgical approach may result in favorable outcome.
Idoia Buldain - One of the best experts on this subject based on the ideXlab platform.
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Study of Humoral Responses against Lomentospora/Scedosporium spp. and Aspergillus fumigatus to Identify L. prolificans Antigens of Interest for Diagnosis and Treatment.
Vaccines, 2019Co-Authors: Idoia Buldain, Aize Pellon, Aitziber Antoran, Aitor Rementeria, Leire Martin-souto, Beñat Zaldibar, Leire Aparicio-fernandez, Maialen Areitio, Emilio Mayayo, Fernando L. HernandoAbstract:The high mortality rates of Lomentospora prolificans infections are due, above all, to the tendency of the fungus to infect weakened hosts, late diagnosis and a lack of effective therapeutic treatments. To identify proteins of significance for diagnosis, therapy or prophylaxis, immunoproteomics-based studies are especially important. Consequently, in this study murine disseminated infections were carried out using L. prolificans, Scedosporium aurantiacum, Scedosporium boydii and Aspergillus fumigatus, and their sera used to identify the most immunoreactive proteins of L. prolificans total extract and secreted proteins. The results showed that L. prolificans was the most virulent species and its infections were characterized by a high fungal load in several organs, including the brain. The proteomics study showed a high cross-reactivity between Scedosporium/Lomentospora species, but not with A. fumigatus. Among the antigens identified were, proteasomal ubiquitin receptor, carboxypeptidase, Vps28, HAD-like hydrolase, GH16, cerato-platanin and a protein of unknown function that showed no or low homology with humans. Finally, Hsp70 deserves a special mention as it was the main antigen recognized by Scedosporium/Lomentospora species in both secretome and total extract. In conclusion, this study identifies antigens of L. prolificans that can be considered as potential candidates for use in diagnosis and as therapeutic targets and the production of vaccines.
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study of humoral responses against Lomentospora scedosporium spp and aspergillus fumigatus to identify l prolificans antigens of interest for diagnosis and treatment
Vaccine, 2019Co-Authors: Idoia Buldain, Aize Pellon, Aitziber Antoran, Aitor Rementeria, Beñat Zaldibar, Maialen Areitio, Emilio Mayayo, Leire Martinsouto, Leire Apariciofernandez, Fernando L. HernandoAbstract:The high mortality rates of Lomentospora prolificans infections are due, above all, to the tendency of the fungus to infect weakened hosts, late diagnosis and a lack of effective therapeutic treatments. To identify proteins of significance for diagnosis, therapy or prophylaxis, immunoproteomics-based studies are especially important. Consequently, in this study murine disseminated infections were carried out using L. prolificans, Scedosporium aurantiacum, Scedosporium boydii and Aspergillus fumigatus, and their sera used to identify the most immunoreactive proteins of L. prolificans total extract and secreted proteins. The results showed that L. prolificans was the most virulent species and its infections were characterized by a high fungal load in several organs, including the brain. The proteomics study showed a high cross-reactivity between Scedosporium/Lomentospora species, but not with A. fumigatus. Among the antigens identified were, proteasomal ubiquitin receptor, carboxypeptidase, Vps28, HAD-like hydrolase, GH16, cerato-platanin and a protein of unknown function that showed no or low homology with humans. Finally, Hsp70 deserves a special mention as it was the main antigen recognized by Scedosporium/Lomentospora species in both secretome and total extract. In conclusion, this study identifies antigens of L. prolificans that can be considered as potential candidates for use in diagnosis and as therapeutic targets and the production of vaccines.
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Microglial immune response is impaired against the neurotropic fungus Lomentospora prolificans.
Cellular Microbiology, 2018Co-Authors: Aize Pellon, Andoni Ramirez-garcia, Idoia Buldain, Aitziber Antoran, Aitor Rementeria, Xabier Guruceaga, Alazne Zabala, Juan Anguita, Carlos Matute, Fernando L. HernandoAbstract:Lomentospora (Scedosporium) prolificans is an opportunistic pathogen capable of causing invasive infections in immunocompromised patients. The fungus is able to disseminate via the bloodstream finally arriving at the central nervous system producing neurological symptoms and, in many cases, patient death. In this context, microglial cells, which are the resident immune cells in the central nervous system, may play an important role in these infections. However, this aspect of anti-L. prolificans immunity has been poorly researched to date. Thus, the interactions and activity of microglial cells against L. prolificans were analysed, and the results show that there was a remarkable impairment in their performance regarding phagocytosis, the development of oxidative burst, and in the production of pro-inflammatory cytokines, compared with macrophages. Interestingly, L. prolificans displays great growth also when challenged with immune cells, even when inside them. We also proved that microglial phagocytosis of the fungus is highly dependent on mannose receptor and especially on dectin-1. Taken together, these data provide evidence for an impaired microglial response against L. prolificans and contribute to understanding the pathobiology of its neurotropism.
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Pathobiology of Lomentospora prolificans: could this species serve as a model of primary antifungal resistance?
International Journal of Antimicrobial Agents, 2018Co-Authors: Aize Pellon, Andoni Ramirez-garcia, Idoia Buldain, Aitziber Antoran, Aitor Rementeria, Leire Martin-souto, Fernando L. HernandoAbstract:The number of fungal isolates resistant to antifungal drugs has increased dramatically over the last few years and has become an important concern for clinicians. Among these isolates, fungi showing multidrug resistance are particularly worrying because of the difficulties associated with their treatment. These factors hamper the successful recovery of patients and drastically raise mortality rates. Antifungal resistance is multifactorial and several mechanisms in different fungi have been described. There is a need to study these mechanisms in depth; however, the study of antifungal drug resistance separately for each individual species makes progress in the field very slow and tedious. The selection of a multiresistant microorganism as a model for understanding resistance mechanisms and extrapolating the results to other species could help in the search for a solution. In this mini-review, we describe the pathobiology of Lomentospora (Scedosporium) prolificans, paying special attention to its intrinsic resistance to all currently available antifungal agents. The characteristics of L. prolificans offer several advantages: the possibility of using a single microorganism for the study of resistance to different drugs, even cases of double and triple resistance; it is biologically safe for society in general as no new genetically-modified strains are needed for the experiments; it is homologous with other fungal species, and there is repetitiveness between different strains. In conclusion, we propose L. prolificans as a candidate for consideration as a fungal model for the study of resistance mechanisms against antifungal agents.
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Molecular and cellular responses of the pathogenic fungus Lomentospora prolificans to the antifungal drug voriconazole.
PLOS ONE, 2017Co-Authors: Aize Pellon, Andoni Ramirez-garcia, Idoia Buldain, Aitziber Antoran, Aitor Rementeria, Fernando L. HernandoAbstract: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.
Thaís Pereira De Mello - One of the best experts on this subject based on the ideXlab platform.
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Biofilms formed by Scedosporium and Lomentospora species: focus on the extracellular matrix.
Biofouling, 2020Co-Authors: Thaís Pereira De Mello, Marta H. Branquinha, André L.s. SantosAbstract:In the present study, the composition of the extracellular matrix (ECM) of the biofilm formed by Scedosporium apiospermum, S. aurantiacum, S. minutisporum and Lomentospora prolificans on a polystyr...
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Saccharide sources do not influence the biofilm formation in Scedosporium/Lomentospora species
Experimental Results, 2020Co-Authors: Thaís Pereira De Mello, Marta H. Branquinha, André L.s. Santos, Michael NevelsAbstract:Scedosporium and Lomentospora species are ubiquitous saprophytic filamentous fungi that emerged as human pathogens with impressive multidrug-resistance profile. The ability to form biofilm over several biotic and abiotic surfaces is one of the characteristics that contributes to their resistance patterns against almost all currently available antifungals. Herein, we have demonstrated that Scedosporium apiospermum, Scedosporium minutisporum, Scedosporium aurantiacum and Lomentospora prolificans were able to form biofilm, in similar amounts, when conidial cells were incubated in a polystyrene substrate containing Sabouraud medium supplemented or not with different concentrations (2%, 5% and 10%) of glucose, fructose, sucrose and lactose. Likewise, the glucose supplementation of culture media primarily composed of amino acids (SCFM, synthetic cystic fibrosis medium) and salts (YNB, yeast nitrogen base) did not modulate the biofilm formation of Scedosporium/Lomentospora species. Collectively, the present data reinforce the ability of these opportunistic fungi to colonize and to build biofilm structures under different environmental conditions.
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Insights into the interaction of Scedosporium apiospermum, Scedosporium aurantiacum, Scedosporium minutisporum, and Lomentospora prolificans with lung epithelial cells
Brazilian Journal of Microbiology, 2019Co-Authors: Thaís Pereira De Mello, Marta H. Branquinha, André L.s. SantosAbstract:Scedosporium spp. and Lomentospora prolificans are filamentous fungi that emerged as human pathogens; however, their mechanisms of virulence/pathogenesis are still largely unknown. In the present work, we have evaluated the interaction of S . apiospermum , S . minutisporum , S . aurantiacum , and L . prolificans with lung epithelial cells (A549 line). The results showed that conidia were able to interact with A549 cells, displaying association indexes of 73.20, 117.98, 188.01, and 241.63 regarding S . apiospermum , L . prolificans , S . minutisporum , and S . aurantiacum , respectively. Light microscopy images evidenced morphological changes in epithelial cells, including rounding and detachment, especially during the interaction with L . prolificans . Plasma membrane injuries were detected in A549 cells after 1 h of co-culturing with S . aurantiacum and S . minutisporum and after 4 h with S . apiospermum and L . prolificans , as judged by the passive incorporation of propidium iodide. After 24 h of fungi-epithelial cells interaction, only mycelia were observed covering the A549 monolayer. Interestingly, the mycelial trap induced severe damage in the A549 cells, culminating in epithelial cell death. Our results demonstrate some relevant events that occur during the contact between lung epithelial cells and Scedosporium/Lomentospora species, including conidial adhesion and hyphal growth with consequent irreversible injury on A549 cells, adding light to the infection process caused by these opportunistic and multidrug-resistant fungi.
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Surface properties, adhesion and biofilm formation on different surfaces by Scedosporium spp. and Lomentospora prolificans.
Biofouling, 2018Co-Authors: Thaís Pereira De Mello, Marta H. Branquinha, Simone S. C. Oliveira, Susana Frases, André L.s. SantosAbstract:AbstractIn the present work, some surface properties of the fungi Scedosporium apiospermum, S. aurantiacum, S. minutisporum, and Lomentospora prolificans and their capability to adhere to and form a biofilm on diverse surfaces were evaluated. All four species had high conidial surface hydrophobicity and elevated electronegative zeta potentials. Abundant quantities of melanin were detected at the conidial surface, whereas sialic acid was absent. The numbers of non-germinated and germinated conidia adhered to poly-L-lysine-covered slides was higher than on glass after 4 h of fungi–surface contact. Additionally, after 72 h of interaction a typical biofilm structure had formed. Mature biofilms were also observed after 72 h on a nasogastric catheter (made from polyvinyl chloride), a late bladder catheter (siliconized latex), and a nasoenteric catheter (polyurethane). Interestingly, biofilm biomass increased considerably when the catheters had previously been incubated with serum. These results confirm that Sce...
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Scedosporium apiospermum, Scedosporium aurantiacum, Scedosporium minutisporum and Lomentospora prolificans: a comparative study of surface molecules produced by conidial and germinated conidial cells.
Memórias do Instituto Oswaldo Cruz, 2018Co-Authors: Thaís Pereira De Mello, Ana Carolina Aor, Diego S. Gonçalves, Sergio Henrique Seabra, Marta H. Branquinha, André L.s. SantosAbstract:BACKGROUND Scedosporium/Lomentospora species are opportunistic mould pathogens, presenting notable antifungal resistance. OBJECTIVES/METHODS We analysed the conidia and germinated conidia of S. apiospermum (Sap), S. aurantiacum (Sau), S. minutisporum (Smi) and L. prolificans (Lpr) by scanning electron microscopy and exposition of surface molecules by fluorescence microscopy. FINDINGS Conidia of Sap, Smi and Sau had oval, ellipsoidal and cylindrical shape, respectively, with several irregularities surrounding all surface areas, whereas Lpr conidia were rounded with a smooth surface. The germination of Sap occurred at the conidial bottom, while Smi and Sau germination primarily occurred at the centre of the conidial cell, and Lpr germination initiated at any part of the conidial surface. The staining of N-acetylglucosamine-containing molecules by fluorescein-labelled WGA primarily occurred during the germination of all studied fungi and in the conidial scars, which is the primary location of germination. Calcofluor white, which recognises the polysaccharide chitin, strongly stained the conidial cells and, to a lesser extent, the germination. Both mannose-rich glycoconjugates (evidenced by fluoresceinated-ConA) and cell wall externally located polypeptides presented distinct surface locations and expression according to both morphotypes and fungal species. In contrast, sialic acid and galactose-containing structures were not detected at fungal surfaces. MAIN CONCLUSIONS The present study demonstrated the differential production/exposition of surface molecules on distinct morphotypes of Scedosporium/Lomentospora species.
Aize Pellon - One of the best experts on this subject based on the ideXlab platform.
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Study of Humoral Responses against Lomentospora/Scedosporium spp. and Aspergillus fumigatus to Identify L. prolificans Antigens of Interest for Diagnosis and Treatment.
Vaccines, 2019Co-Authors: Idoia Buldain, Aize Pellon, Aitziber Antoran, Aitor Rementeria, Leire Martin-souto, Beñat Zaldibar, Leire Aparicio-fernandez, Maialen Areitio, Emilio Mayayo, Fernando L. HernandoAbstract:The high mortality rates of Lomentospora prolificans infections are due, above all, to the tendency of the fungus to infect weakened hosts, late diagnosis and a lack of effective therapeutic treatments. To identify proteins of significance for diagnosis, therapy or prophylaxis, immunoproteomics-based studies are especially important. Consequently, in this study murine disseminated infections were carried out using L. prolificans, Scedosporium aurantiacum, Scedosporium boydii and Aspergillus fumigatus, and their sera used to identify the most immunoreactive proteins of L. prolificans total extract and secreted proteins. The results showed that L. prolificans was the most virulent species and its infections were characterized by a high fungal load in several organs, including the brain. The proteomics study showed a high cross-reactivity between Scedosporium/Lomentospora species, but not with A. fumigatus. Among the antigens identified were, proteasomal ubiquitin receptor, carboxypeptidase, Vps28, HAD-like hydrolase, GH16, cerato-platanin and a protein of unknown function that showed no or low homology with humans. Finally, Hsp70 deserves a special mention as it was the main antigen recognized by Scedosporium/Lomentospora species in both secretome and total extract. In conclusion, this study identifies antigens of L. prolificans that can be considered as potential candidates for use in diagnosis and as therapeutic targets and the production of vaccines.
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study of humoral responses against Lomentospora scedosporium spp and aspergillus fumigatus to identify l prolificans antigens of interest for diagnosis and treatment
Vaccine, 2019Co-Authors: Idoia Buldain, Aize Pellon, Aitziber Antoran, Aitor Rementeria, Beñat Zaldibar, Maialen Areitio, Emilio Mayayo, Leire Martinsouto, Leire Apariciofernandez, Fernando L. HernandoAbstract:The high mortality rates of Lomentospora prolificans infections are due, above all, to the tendency of the fungus to infect weakened hosts, late diagnosis and a lack of effective therapeutic treatments. To identify proteins of significance for diagnosis, therapy or prophylaxis, immunoproteomics-based studies are especially important. Consequently, in this study murine disseminated infections were carried out using L. prolificans, Scedosporium aurantiacum, Scedosporium boydii and Aspergillus fumigatus, and their sera used to identify the most immunoreactive proteins of L. prolificans total extract and secreted proteins. The results showed that L. prolificans was the most virulent species and its infections were characterized by a high fungal load in several organs, including the brain. The proteomics study showed a high cross-reactivity between Scedosporium/Lomentospora species, but not with A. fumigatus. Among the antigens identified were, proteasomal ubiquitin receptor, carboxypeptidase, Vps28, HAD-like hydrolase, GH16, cerato-platanin and a protein of unknown function that showed no or low homology with humans. Finally, Hsp70 deserves a special mention as it was the main antigen recognized by Scedosporium/Lomentospora species in both secretome and total extract. In conclusion, this study identifies antigens of L. prolificans that can be considered as potential candidates for use in diagnosis and as therapeutic targets and the production of vaccines.
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Microglial immune response is impaired against the neurotropic fungus Lomentospora prolificans.
Cellular Microbiology, 2018Co-Authors: Aize Pellon, Andoni Ramirez-garcia, Idoia Buldain, Aitziber Antoran, Aitor Rementeria, Xabier Guruceaga, Alazne Zabala, Juan Anguita, Carlos Matute, Fernando L. HernandoAbstract:Lomentospora (Scedosporium) prolificans is an opportunistic pathogen capable of causing invasive infections in immunocompromised patients. The fungus is able to disseminate via the bloodstream finally arriving at the central nervous system producing neurological symptoms and, in many cases, patient death. In this context, microglial cells, which are the resident immune cells in the central nervous system, may play an important role in these infections. However, this aspect of anti-L. prolificans immunity has been poorly researched to date. Thus, the interactions and activity of microglial cells against L. prolificans were analysed, and the results show that there was a remarkable impairment in their performance regarding phagocytosis, the development of oxidative burst, and in the production of pro-inflammatory cytokines, compared with macrophages. Interestingly, L. prolificans displays great growth also when challenged with immune cells, even when inside them. We also proved that microglial phagocytosis of the fungus is highly dependent on mannose receptor and especially on dectin-1. Taken together, these data provide evidence for an impaired microglial response against L. prolificans and contribute to understanding the pathobiology of its neurotropism.
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Pathobiology of Lomentospora prolificans: could this species serve as a model of primary antifungal resistance?
International Journal of Antimicrobial Agents, 2018Co-Authors: Aize Pellon, Andoni Ramirez-garcia, Idoia Buldain, Aitziber Antoran, Aitor Rementeria, Leire Martin-souto, Fernando L. HernandoAbstract:The number of fungal isolates resistant to antifungal drugs has increased dramatically over the last few years and has become an important concern for clinicians. Among these isolates, fungi showing multidrug resistance are particularly worrying because of the difficulties associated with their treatment. These factors hamper the successful recovery of patients and drastically raise mortality rates. Antifungal resistance is multifactorial and several mechanisms in different fungi have been described. There is a need to study these mechanisms in depth; however, the study of antifungal drug resistance separately for each individual species makes progress in the field very slow and tedious. The selection of a multiresistant microorganism as a model for understanding resistance mechanisms and extrapolating the results to other species could help in the search for a solution. In this mini-review, we describe the pathobiology of Lomentospora (Scedosporium) prolificans, paying special attention to its intrinsic resistance to all currently available antifungal agents. The characteristics of L. prolificans offer several advantages: the possibility of using a single microorganism for the study of resistance to different drugs, even cases of double and triple resistance; it is biologically safe for society in general as no new genetically-modified strains are needed for the experiments; it is homologous with other fungal species, and there is repetitiveness between different strains. In conclusion, we propose L. prolificans as a candidate for consideration as a fungal model for the study of resistance mechanisms against antifungal agents.
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Molecular and cellular responses of the pathogenic fungus Lomentospora prolificans to the antifungal drug voriconazole.
PLOS ONE, 2017Co-Authors: Aize Pellon, Andoni Ramirez-garcia, Idoia Buldain, Aitziber Antoran, Aitor Rementeria, Fernando L. HernandoAbstract: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.
