Fosmanogepix Therapy of Disseminated Fusarium Infection.

Invasive Fusarium infections cause high mortality. Fosmanogepix, a first-in-class antifungal agent, has potent activity against Fusarium. A patient with acute leukemia with invasive fusariosis, probably involving the central nervous system and caused by Fusarium lactis resistant to currently available antifungal agents, was cured of her infection with fosmanogepix. Fosmanogepix was well tolerated.

Untargeted 1 H-NMR Metabolome of Celery During Fusarium Wilt: Implications for Vegetable Quality.

Celery is a vegetable widely consumed as a condiment to prepare diverse dishes around the world. Nevertheless, this plant is susceptible to the attack of several phytopathogens including those of the Fusarium genus which is translated into devastating losses for the production chain. Herein we report on the metabolic changes produced during the celery wilt caused by Fusarium oxysporum which was determined through untargeted 1 H-NMR metabolomics. The changes in the metabolite content of celery were measured at 16, 24, and 32 days post-inoculation using viable conidia obtained from the native F. oxysporum strain FO3. Our results demonstrated that the parasitic activity of the fungus reduced the endogenous levels of free sugars (fructose, galactose, glucose isomers, mannose, Myo-inositol, mannitol, and sucrose) amino acids (alanine, aspartate GABA, glutamate, glutamine, histidine, isoleucine, leucine, methionine, proline, threonine, tyrosine, and valine), nucleosides (adenosine, cytidine, guanosine, and uridine) and organic acids (citric acid, fumaric acid, malic acid, and succinic acid). Interestingly, the levels of tyrosine and tryptophan were triggered as a consequence of F. oxysporum infection. This tendency was correlated with an increase in the levels of chlorogenic acid, apiin, and apigenin derivatives, suggesting their involvement in the chemical defense of celery against fungal colonization. According to principal component analysis (PCA) and Orthogonal Projections to Latent Structures Discriminant Analysis (OPLS-DA) methanol was the main differential metabolite and it was considered as a new chemical marker associated with F. oxysporum infection. Our results demonstrate that infected celery plants dramatically reduced their nutritional and nutraceutical contents during Fusarium wilt after 32 days post-inoculation. However, these findings also suggest that the phenylpropanoid pathway is strongly related with the chemical defense of celery against F. oxysporum.

Systemic Fusariosis: A Rare Complication in Children with Acute Lymphoblastic Leukemia.

Fusarium species are ubiquitous pathogens causing opportunistic infections in immunocompromised patients. Clinical presentation depends on a host's immunity and can be localized or disseminated. Since there are few reports of disseminated fusariosis in children, we described an unusual case of Fusarium solani infection in a 9-year-old child with acute lymphoblastic leukemia (ALL). This patient presented a deep wound in the elbow at diagnosis. During the induction phase of chemotherapy, he developed multiple skin lesions and severe pneumonia; Fusarium solani was cultured from the skin lesions. He was treated with a high dose of liposomal amphotericin B, followed by voriconazole. Starting from this peculiar case, we collected all patients with acute leukemia affected by Fusarium infection, treated in the pediatric Onco-Hematology Division of Padua University Hospital during the last 20 years. We identified another six cases: all these patients were affected by acute myeloid leukemia (AML) and five of them presented a relapsed/refractory disease. Two out of seven patients died because of infection; five patients recovered from infection, but three out of seven died because of leukemia. Skin lesions in immunocompromised patients should rise the suspicion of disseminated fusariosis. Furthermore, considering the emergence of filamentous fungi in immunocompromised patients, we all should be aware of Fusarium infection, reminding us that the diagnosis is important to cure the infection.

Eggs of tegu lizard, Salvator merianae (Duméril & Bilbron, 1839) (Squamata; Teiidae) damaged by fungal infections / Ovos de lagarto tegu, Salvator merianae (Duméril e Bilbron, 1839) (Squamata; Teiidae) danificados por infecções fúngicas

Abstract The tegu (Salvator merianae) is the largest lizard found in Brazil and has a wide distribution, occurring in several biomes. The presence of fungi on reptilian eggs initially occurs on infertile eggs, which leads to a subsequent infection in fertile eggs, causing damage and death of embryos. The objective of this study was to identify the fungi that caused lesions in the eggs of tegu in captivity. Swabs were collected on infected and healthy eggshells, in an embryo that died and the substrate of the incubation box. Samples were submitted to saboraund dextrose agar. A total of 93.3% of positive samples were obtained for the fungi Fusarium (11/14), Trichoderma (1/15), Penicilium (1/15), Mucor (1/15), and yeasts of the genus Trichosporon. Therefore, Fusarium was the main agent that caused the lesion and death of embryos in the eggs of the tegu lizard. Sanitary control methods may be taken to avoid fungal infections in the eggs.

Resumo O teiú (Salvator merianae) é o maior lagarto encontrado no Brasil e possui ampla distribuição, sendo encontrado em vários biomas. A presença de fungos em ovos de répteis ocorre inicialmente em ovos inférteis, o que leva à uma infecção posterior em ovos férteis, gerando danos e morte dos embriões. O objetivo deste estudo foi o de identificar os fungos geradores de lesões em ovos de teiú em cativeiro. Foram coletados suabes na casca de ovos infectados e sadios, além de um embrião que veio a óbito, e do substrato presente na caixa de incubação. As amostras foram submetidas ao cultivo em ágar Saboraund dextrose. Um total de 93,3% de amostras foram positivas para os fungos Fusarium (11/15), Trichoderma (1/15), Penicillium (1/15), Mucor (1/15) e leveduras do gênero Trichosporon (3/15). Logo, Fusarium foi o principal agente causador das lesões e morte de embriões nos ovos do lagarto teiú. Métodos de controle sanitário podem ser adotados para evitar infecção fúngicas nos ovos.

Fusarium species intramedullary spinal cord fungus ball: case report.

The Fusarium species are one of the most common opportunistic fungal infections occurring in immunocompromised patients and are associated with high morbidity and mortality. Common sites of infection include blood, skin, nasal passages, lungs, bone, and other visceral organs. There is a paucity of literature on Fusarium infections in the brain, and the true nature and extent of central nervous system involvement is not well described. To the authors' knowledge, there have been no reported cases of Fusarium infection of the spine. The authors report the case of a man with acute myeloblastic leukemia and resultant pancytopenia who presented with fungal sinusitis, upper- and lower-extremity weakness, and cardiopulmonary arrest. Imaging studies revealed a spinal cervical intramedullary ring-enhancing lesion. Because of the progressive nature of his symptoms, neurosurgical intervention involving a C2-3 laminectomy and drainage of the lesion was performed. Intraoperative cultures and histopathology results were positive for Fusarium species and, along with intraoperative findings, were consistent with a fungus ball. The patient was placed on a regimen of intravenous and intrathecal antifungal therapy. Unfortunately, his clinical condition declined postoperatively, and he ultimately died of disseminated infection.

Fusarium infection-induced partial failure of free anterolateral thigh musculocutaneous flap: Case report.

Fusarium species, a soil-borne fungi, causes disease in animals and humans, particularly in immunocompromized patients. A 62-year-old male presented with type II diabetes mellitus, diagnosed 4 years ago. He had a motorcycle accident-caused open tibiofibular fracture of the left lower extremity (Gustilo grade IIIb). With open reduction and internal fixation, an anterolateral thigh musculocutaneous flap was harvested for coverage of exposed bone and defect reconstruction. Partial failure of the flap occurred 9 days following reconstruction, and histological examination revealed Fusarium spp. After treatment with antifungal drugs and debridement, we performed a split-thickness skin graft. At 2-year follow-up, the flap was viable with adequate bone union. This is the first reported case of partial flap failure due to a Fusarium spp. infection. Possibility of fungal infections in patients with late-onset flap failure should be noted. Prompt diagnosis and treatment are needed to prevent repeated free-tissue transfer and/or devastating outcomes.

Disseminated fusariosis emerged from prolonged local genital infection after cord blood transplantation.

Disseminated fusariosis (DF) is a rare life threatening fungal infection in immunocompromised hosts. We herein report a case of a fatal DF mimicking varicella zoster virus (VZV) infection that was emerged from a localized genital infection during cord blood transplantation (CBT) in a patient with severe aplastic anemia (SAA). The patient developed an ulcer following small painful vesicles mimics herpes simplex virus infection (HSV) on the glans penis before CBT, but a Fusarium species was identified. Despite administration of voriconazole, liposomal amphotericin B and granulocyte transfusion, the lesion was extended to extensive skin looked like VZV infection and the patients died after CBT. Massive fusarium infiltration was detected in multiple organs at autopsy. A genetic analysis of the mold identified Fusarium solani after his death. It should be noted that in patients with fusarium infection, localized and disseminated lesions of fusarium infection sometimes mimic HSV and VZV infections, which hampers an early diagnosis.

The cinnamyl alcohol dehydrogenase family in flax: Differentiation during plant growth and under stress conditions.

Cinnamyl alcohol dehydrogenase (CAD), which catalyzes the reduction of cinnamaldehydes to their alcohol derivatives, is represented by a large family of proteins. The aim of the study was to identify the CAD isoforms in flax (Linum usitatissimum L.) - LuCADs - and to determine their specificity to enhance knowledge of the mechanisms controlling cell wall lignification in flax under environmental stresses. On the basis of genome-wide analysis, we identified 15 isoforms (one in two copies) belonging to three major classes of the CAD protein family. Their specificity was determined at the transcriptomic level in different tissues/organs, under Fusarium infection and abiotic stresses. Considering the function of particular LuCADs, it was established that LuCAD1 and 2 belong to Class I and they take part in the lignification of maturing stem and in the response to cold and drought stress. The Class II members LuCAD3, LuCAD4, LuCAD5 and LuCAD6 play various roles in flax being putatively responsible for lignin synthesis in different organs or under certain conditions. The obtained results indicate that within Class II, LuCAD6 was the most abundant in seedlings and maturing stems, LuCAD3 in leaves, and LuCAD4 in stems. Comparative analysis showed that expression of LuCAD genes in roots after F. oxysporum infection had the greatest contribution to differentiation of LuCAD expression patterns. Surprisingly, most of the analyzed LuCAD isoforms had reduced expression after pathogen infection. The decrease in mRNA level was primarily observed for LuCAD6 and LuCAD4, but also LuCAD1 and 8. However, the induction of LuCAD expression was mostly characteristic for Class I LuCAD1 and 2 in leaves. For cold stress, a clear correlation with phylogenic class membership was observed. Low temperatures caused induction of CAD isoforms belonging to Class I and repression of LuCADs from Class III.

Eggs of tegu lizard, Salvator merianae (Duméril & Bilbron, 1839) (Squamata; Teiidae) damaged by fungal infections

Abstract The tegu (Salvator merianae) is the largest lizard found in Brazil and has a wide distribution, occurring in several biomes. The presence of fungi on reptilian eggs initially occurs on infertile eggs, which leads to a subsequent infection in fertile eggs, causing damage and death of embryos. The objective of this study was to identify the fungi that caused lesions in the eggs of tegu in captivity. Swabs were collected on infected and healthy eggshells, in an embryo that died and the substrate of the incubation box. Samples were submitted to saboraund dextrose agar. A total of 93.3% of positive samples were obtained for the fungi Fusarium (11/14), Trichoderma (1/15), Penicilium (1/15), Mucor (1/15), and yeasts of the genus Trichosporon. Therefore, Fusarium was the main agent that caused the lesion and death of embryos in the eggs of the tegu lizard. Sanitary control methods may be taken to avoid fungal infections in the eggs.

Resumo O teiú (Salvator merianae) é o maior lagarto encontrado no Brasil e possui ampla distribuição, sendo encontrado em vários biomas. A presença de fungos em ovos de répteis ocorre inicialmente em ovos inférteis, o que leva à uma infecção posterior em ovos férteis, gerando danos e morte dos embriões. O objetivo deste estudo foi o de identificar os fungos geradores de lesões em ovos de teiú em cativeiro. Foram coletados suabes na casca de ovos infectados e sadios, além de um embrião que veio a óbito, e do substrato presente na caixa de incubação. As amostras foram submetidas ao cultivo em ágar Saboraund dextrose. Um total de 93,3% de amostras foram positivas para os fungos Fusarium (11/15), Trichoderma (1/15), Penicillium (1/15), Mucor (1/15) e leveduras do gênero Trichosporon (3/15). Logo, Fusarium foi o principal agente causador das lesões e morte de embriões nos ovos do lagarto teiú. Métodos de controle sanitário podem ser adotados para evitar infecção fúngicas nos ovos.

An outbreak of invasive fusariosis in a children's cancer hospital.

Fusarium is considered an emerging pathogen, and there are few reports of fusariosis in children. The objective of this study was to describe an outbreak of invasive fusariosis in a children's cancer hospital. A neutropenic 17-year-old male patient hospitalized for 10 days for a relapse of acute myeloid leukaemia, under chemotherapy, presented fever without any other symptoms; a thoracic computerized tomography showed bilateral pulmonary nodules. During voriconazole treatment, 1-cm reddened and painful subcutaneous nodules appeared on arms and legs and the culture of a skin biopsy revealed F. solani. Another case occurred 11 days later and started an outbreak investigation. Water samples for cultures were collected from taps, showers and water reservoirs. Air from all patient rooms was sampled. Faucets and the drains of sinks and showers were swabbed and cultured. Environmental and clinical isolates were typed. There were 10 confirmed cases of infection caused by Fusarium spp. F. oxysporum and F. solani were isolated from water, swabs and air in patient rooms. Many control measures were instituted, but the outbreak was only controlled 1 year after the first case, when water filters filtering 0.2 µm were installed at the exit of all faucets and showers in all patient rooms (points-of-use). Typing demonstrated that clinical isolates of F. oxysporum were similar to those of the environment. In conclusion, to our knowledge this is the first reported outbreak of invasive fusariosis in children with oncohaematologic disease. It was controlled using 0.2-µm filters in all tap faucets and showers.