Infección fúngica invasiva por Saprochaete capitata en un niño con aplasia medular / Invasive fungal infection by Saprochaete capitata in a child with bone marrow aplasia

RESUMEN Saprochaete capitata es una causa rara de infección fúngica invasiva en pacientes inmunocomprometidos con alta mortalidad y resistencia antifúngica. Presentamos el caso de un niño de cinco años con diagnóstico de aplasia medular, sometido a trasplante de progenitores hematopoyéticos (TPH), que cursó con neutropenia febril persistente, dolor abdominal intenso, aparición de lesiones maculopapulares en piel y deterioro de la función renal. Se identificó la presencia de S. capitata, en hemocultivos transcatéter venoso central. Esta infección fúngica invasiva resulta ser rara, pero emergente y potencialmente mortal, en pacientes con neutropenia febril persistente y uso prolongado de dispositivos invasivos intravasculares como catéter venoso central.

ABSTRACT Saprochaete capitata is a rare cause of invasive fungal infection in immunocompromised patients with high mortality and antifungal resistance. We present the case of a 5-year-old boy with bone marrow aplasia, who underwent hematopoietic stem cell transplantation (HSCT) and presented persistent febrile neutropenia, abdominal pain, appearance of maculopapular lesions on the skin, and impaired renal function. The presence of S. capitata was identified by blood culture from a central venous catheter. This invasive fungal infection is rare but emergent and life-threatening, especially in immunocompromised patients with persistent febrile neutropenia and prolonged use of invasive devices such as central venous catheters.

Computational fluid dynamics analysis of Trichosporon fermentans flocculation in refined soybean oil wastewater and flocculation rate prediction method.

Trichosporon fermentans can be used to treat refined soybean oil wastewater (RSOW) and produce microbial lipids. Bioflocculation is an effective method to recover Trichosporon fermentans which accumulates intracellular oils from wastewater. During the flocculation, the hydrodynamic distribution and parameters in the reactor are important limiting factors of yeast flocculation performance. In a 0.25 L flocculation device, it was found that the appropriate range of turbulence kinetic energy was within 0.00065-0.00073 m2/s2, the dissipation rate was within 0.119-0.317 m2/s3, and the shear force was less than 0.433 Pa by computational fluid dynamics. In this case, the flocculation rate (Fr) of Trichosporon fermentans could reach more than 90%. The empirical formula associated Fr of Trichosporon fermentans with hydrodynamic parameters was obtained by Matlab, and improved in the enlargement of flocculation device, displaying an error of less than 3.03%. A conical draft tube airlift circulating reactor for flocculation was designed based on the empirical formula, and the Fr reached 91.3%. The study shows that it is feasible to predict Fr of Trichosporon fermentans according to hydrodynamic parameters by numerical simulation, and design the industrial reactor for flocculation harvesting yeasts. It is also helpful for large-scale treatment of RSOW in a safe environment.

Geotrichum spp: An overlooked and fatal etiologic agent in immunocompromised patients. A case series from a referral center in Mexico.

Geotrichum spp. is an emergent pathogen. We aimed to describe Geotrichum spp. invasive fungal infections (IFI) in patients from Mexico. We reviewed cases with Geotrichum spp. isolated in clinical samples, from 2001 to 2019. Descriptive analysis was used for clinical data. Twenty patients with proven/probable Geotrichum spp. IFI were analyzed. The median age was 43; 55% were males. Hematologic malignancy was found in 60% (12/20); 75% (15/20) received systemic immunosuppressors. The most common presentation was lower respiratory tract infection. In-hospital mortality was 45% (9/20). Geotrichum spp. should be acknowledged as a pathogen causing atypical pneumonia in immunocompromised Latin American patients. LAY SUMMARY: Geotrichum spp. causes invasive infection in immunocompromised hosts. We describe a case series of 20 patients from Mexico City. Hematologic malignancy was the most common comorbidity. Clinical presentation was mainly lower respiratory tract infection. Mortality was high despite antifungal therapy.

ß-1,3-d-Glucan and Galactomannan as Biomarkers for the Detection of Invasive Geotrichum and Magnusiomyces Infections: a Retrospective Evaluation.

Magnusiomyces and Geotrichum species are ascomycetous yeasts that can cause potentially life-threatening invasive fungal infections commonly referred to as geotrichosis. In this study, we aimed to estimate the incidence and mortality of these infections in a German tertiary care center. Furthermore, we evaluated the suitability of the fungal biomarkers galactomannan (GM) and ß-1,3-d-glucan (BDG), which are both recommended as surrogate markers for Magnusiomyces capitatus infection by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and the European Confederation of Medical Mycology (ECMM) joint clinical guidelines for the diagnosis and management of rare invasive yeast infections for detection of invasive geotrichosis. Cases meeting the inclusion criteria for invasive Magnusiomyces/Geotrichum infection were retrospectively identified. Serum samples and culture supernatants were analyzed with two commercially available fungal antigen tests (Platelia Aspergillus Ag EIA and Wako ß-glucan test). For a control cohort, outpatient samples sent for lues testing were included. Thirty-eight cases of Magnusiomyces/Geotrichum infection were identified over an 11-year observation period. In the majority of cases, the fungus was isolated from intra-abdominal specimens of patients with a history of abdominal surgery/procedures (n = 32). All cases of fungemia occurred exclusively in haemato-oncologic patients (n = 14). Thirty-day survival was 42% in the fungemia and 43% in the intra-abdominal geotrichosis group. Serum samples were available for 23 patients (14 bloodstream and nine intra-abdominal infections). While BDG sensitivity was 65%, none of the sera was GM positive. This finding was supported by in vitro experiments analyzing fungal culture supernatants: M. capitatus secretes significant amounts of BDG but not GM. Specificity was 96% for BDG and 100% for GM. Magnusiomyces and Geotrichum infections are not limited to haemato-oncologic patients. Contrasting the current ESCMID/ECMM recommendation, our results indicate that GM is no suitable biomarker for the diagnosis of Magnusiomyces infection. Contrarily, BDG sensitivity is comparable to that of candidemia.

Critically ill patients with severe infections related to Geotrichum species: A French retrospective multicentre study.

OBJECTIVES: Geotrichum spp can be responsible for severe infections in immunocompromised patients. We aim to describe Geotrichum-related infections in the ICU and to assess risk factors of mortality. METHODS: Retrospective multicentre study, conducted in 14 French ICUs between 2002 and 2018, including critically ill adult patients with proven or probable infection related to Geotrichum species. Data were obtained from the medical charts. RESULTS: Thirty-six patients, median age 60 years IQR [53; 66] were included. Most of the patients had haematological malignancies (78%). The reason for ICU admission was shock in half of the patients (n = 19, 53%) and respiratory failure in thirteen patients (36%). Median SOFA score was 8.5 IQR [7; 15]. Time between ICU admission and fungal diagnosis was 2.5 days [-1; 4]. Infection was disseminated in 27 (75%) patients with positive blood cultures in 25 patients (69%). Thirty patients (83%) received curative antifungal treatment in the ICU, in a median time of 1 day [0;1] after ICU admission. Twenty-four patients (67%) died in the ICU and hospital mortality rate was 69%. The number and extent of organ failures, as represented by SOFA score, were associated with mortality. CONCLUSIONS: This study demonstrates poor outcome in critically ill patients with Geotrichum-related infections, which encourages a high level of suspicion.

Calidad microbiológica del aire en seis áreas de la microestación biológica- Zoocriadero de la Universidad Nacional Agraria de la Selva ­ Tingo María ­ Perú / Microbiological quality of air in six areas of the biological micro station - Zoocriadero of the Universidad Nacional Agraria de la Selva - Tingo Maria ­ Peru

El presente trabajo de investigación tiene como objetivo evaluar la calidad microbiológica del aire en seis áreas de la Microestación Biológica-Zoocriadero de la Universidad Nacional Agraria de la Selva-Tingo María-Perú; procediéndose de la siguiente manera: Se seleccionaron seis áreas de muestreo (A1: Boletería, A2: Caseta gallito de las rocas, A3: Zona de las tortugas, A4: Caseta del otorongo, A5: Caseta de los monos y A6: Cocina), de los cuales para la determinación de los parámetros físicos (PAS, temperatura, humedad relativa, precipitación y rosa de viento) se obtuvo información de la estación meteorológica de la UNAS y de lecturas directas en campo, para la determinación de las PAS se realizó por el método pasivo obteniéndose la mayor concentración de PAS en el área 1 "Boletería" (12.61 t/km2/mes, 11.08 t/km2/mes y 8.4 t/km2/mes) y la más baja en el área 5 "caseta de los monos" (2.80 t/km2/mes, 2.80 t/km2/mes y 3.2 t/km2/mes); para el análisis microbiológico se realizó por el método de borboteo en líquidos, identificándose 27 géneros entre bacterias y hongos, siendo las bacterias más frecuentes Bacillus sp., Staphylococcus sp., Enterobacter agglomerans, Klebsiella pneumoniae, Enterobacter hafniae y algunas bacterias patógenas para el hombre como Streptococcus sp., Clostridium perfringens, Bacillus anthracis. Los hongos de mayor frecuencia son Penicillium sp., Aspergillius sp., Geotrichum sp., algunos hongos patógenos identificados: Microsporum sp., Epirophyton sp. Por otro lado, para la percepción del público como trabajadores se aplicó encuestas, donde indicaron que la calidad microbiológica del aire en la Microestación Biológica-Zoocriadero es regular(AU)

The objective of this research paper is to assess the microbiological quality of the air in six areas of the Biologial Micro-station and animal breeding farm of the Peruvian Univeristy "Universidad Nacional Agraria de la Selva in Tingo María, Perú", proceeding as follows: Six sampling areas were selected (A1: Ticket Office, A2: Cock-of-the-Rock hut, A3: Turtle area, A4: Otorongo hut, A5: Monkey hut, A6: Kitchen), of wich for the determination of the phisical parameters (SBP, temperature, relative humidity, precipitation and wind rose) information was obtained from the UNAS meteorological station and direct readings in the field. For the determination of SBP was performed by the passive method obtaining the high concentration of SBP in area 1 "Ticket Office" (12.61 t/km2/month, 11.08 t/km2/month and 8.4 t/km2/month) and the lowest in area 5 "monkey house" (2.80 t/km2/month, 2.80 t/km2/month and 3.2 t/km2/month); microbiological analysis was performed by the liquid bubbling method, identifying 27 genera incluiding bacteria and fungi, with the most frequent bacteria being Bacillus sp., Staphylococcus sp., Enterobacter agglomerans, Klebsiella pneumoniae, Enterobacter hafniae and some bacteria pathogenic for humans such as Streptococcus sp., Clostridium perfringens and Bacillus anthracis. The most frequent fungi are Penicillium sp., Aspergillius sp. and Geotrichum sp.; some pathogenic fungi identified: Microsporum sp., Epirophyton sp. On the other hand,regarding the perception of the public and workers, surveys were applied, wich indicated that the microbiologial quality of the air in the Biological Micro-station and animal breeding farm is regular(AU)

Cinnamaldehyde promotes the defense response in postharvest citrus fruit inoculated with Penicillium digitatum and Geotrichum citri-aurantii.

Induced resistance in harvested fruit and vegetables is a superior strategy to reduce postharvest decay. In the present study, Cinnamaldehyde (CA) was applied to investigate for its induced resistance against Penicillium digitatum and Geotrichum citri-aurantii. The results showed that 5250 mg CA/L wax was effective concentration in inducing the resistance of citrus fruit to green mold and sour rot. Wax+ CA (WCA) reduced significantly green mold and sour rot incidences at different exposure times, with 24 h being the optimal exposure time. The host reactions under infection with different pathogens were similar. During initial exposure, treatment with 5250 mg CA/L wax enhanced significantly the activities of phenylalanine ammonia-lyase (PAL), peroxidase (POD), polyphenol oxidase (PPO), ß-1, 3-glucanase (GLU) and chitinase (CHT) in the presence of direct contact with the pathogen. Simultaneously, WCA induced an increase in total phenolic, flavanone and dihydroflavonol, flavone and flavonol, and lignin contents. Thus, our results suggest that treatment using 5250 mg CA/L wax can be applied early to control diseases by provoking response reactions in citrus fruit.

Metschnikowia citriensis FL01 antagonize Geotrichum citri-aurantii in citrus fruit through key action of iron depletion.

Metschnikowia citriensis FL01 has great potential for biocontrol applications for its excellent biocontrol efficacy on postharvest diseases of citrus fruit, and the iron depletion by pulcherriminic acid (PA) and then formation of insoluble pigment pulcherrimin had been speculated as an important action mechanism. To identify the genes involved in pulcherrimin synthesis and reutilization in M. citriensis FL01, we de novo assembled the genome of M. citriensis FL01 based on long-read PacBio sequencing. The final assembled genome consisted of 12 contigs with a genome size of 25.74 Mb, G + C content of 49.16% and 9310 protein-coding genes. The genome-wide BLAST of the PUL genes of M. pulcherrima APC 1.2 showed that the four PUL genes were clustered and located on Contig 4 of M. citriensis FL01. In order to further clarify the role of pulcherrimin pigment on biocontrol of M. citriensis FL01, CRISPR/cas9 technology was used to knock out PUL2 gene that was responsible for PA synthesis and the pigmentless mutants with stable phenotype were obtained. The mutant strains of M. citriensis FL01 lost the ability to produce pulcherrimin pigment, and simultaneously lost the ability to inhibit the growth of Geotrichum citri-aurantii in vitro. Moreover, the biocontrol efficacy of pigmentless mutant strains against sour rot was about 80% lower than that of wild-type M. citriensis FL01. These results directly proved that the iron depletion was an important mechanism of M. citriensis FL01.

Peppermint Essential Oil Suppresses Geotrichum citri-aurantii Growth by Destructing the Cell Structure, Internal Homeostasis, and Cell Cycle.

Peppermint essential oil (Peo) is an efficient antifungal agent, and 2.0 µL of Peo per milliliter culture medium can completely inhibit the mycelium growth and spore germination of Geotrichum citri-aurantii. In vitro experiments showed that the main functional component in Peo was l-menthol, which could lead to changes in sugar and protein contents, reduce the content of alkaline phosphatase (AKP), and destroy the spore membrane structure, with a significant increase in electrical conductivity. Meanwhile, the content of reactive oxygen (ROS) accumulated sharply, and the enzyme activity changed significantly with the change in the gene expression level. In addition, l-menthol could cause degradation in spore genetic material differently. Furthermore, a total of 1704 differentially expressed genes (DEGs) in G. citri-aurantii after 1.6 µL/mL l-menthol exposure for 2 h were obtained by the transcriptome sequencing. These DEGs were involved in transmembrane transport, carbohydrate transmembrane transport protein activity, and mitogen-activated protein kinase (MAPK) signaling pathway. The protein-protein interaction (PPI) analysis of DEGs yielded 10 highly cross-linked nodes, and these genes were associated with DNA replication and cell cycle. The expression level of the hub gene was confirmed by real-time quantitative PCR (RT-qPCR), with the most significant changes in POL 30 (5.9-fold). Molecular simulation was performed and it was found that the binding site between l-menthol and POL 30 was the 44th ARG residue in POL 30, and it was speculated that l-menthol and POL 30 may be combined by hydrogen bonding interaction. The results of flow cytometry assay showed that l-menthol blocked the replication process in the S-phase of G. citri-aurantii. This study provides new insights into the development and application of Peo in food safety.

Efficient biosynthesis of (S)-1-[2-(trifluoromethyl)phenyl]ethanol by a novel isolate Geotrichum silvicola ZJPH1811 in deep eutectic solvent/cyclodextrin-containing system.

This study aimed to develop a biotransformation process for the production of (S)-1-[2-(trifluoromethyl)phenyl]ethanol, a key chiral intermediate of Plk1 inhibitor, and increase its productivity through medium engineering strategy. A fungus isolate Geotrichum silvicola ZJPH1811 was adopted as biocatalyst for 2'-(trifluoromethyl)acetophenone reduction, and gave the best performance with > 99.2% product ee. To improve the yield, choline acetate/cysteine (ChAc/Cys) was introduced as co-solvent in reaction system, which accelerated mass transfer and protected cells from substrate inhibition. Moreover, a synergistic effect of methylated-ß-cyclodextrin (MCD) and ChAc/Cys was found in the bioreduction, with further enhancement in substrate concentration and cell membrane permeability. Compared with buffer system, in the developed ChAc/Cys-MCD-containing system, substrate loading and product yield were increased by 6.7-fold and 2.4-fold respectively. This is the first report on (S)-1-[2-(trifluoromethyl)phenyl]ethanol production with G. silvicola, and provides valuable insight into the synergistic effect of DES and CDs in biocatalysis.

Thymol Encapsulated into HP-ß-Cyclodextrin as an Alternative to Synthetic Fungicides to Induce Lemon Resistance against Sour Rot Decay.

Consumers demand the use of eco-friendly fungicides to treat fruit and vegetables and governmental authorities have unauthorized the application of chemical antifungals for the efficient control of sour rot. In the present research, the microwave irradiation (MW) method was used to encapsulate thymol into 2-hydroxylpropyl-beta-cyclodextrin (HP-ß-CD) and the effect of these HP-ß-CD on controlling sour rot in citrus fruit, caused by Geotrichum citri-aurantii, was evaluated. Amounts of 25 and 50 mM of HP-ß-CD-thymol were used, and compared with propiconazole, to control the decay of inoculated lemon fruit. The treatments were performed in curative and preventive experiments. The incidence and severity of Geotrichum citri-aurantii in 25 and 50 mM HP-ß-CD-thymol-treated fruit were reduced in both experiments. The preventive 50 mM HP-ß-CD-thymol treatment showed the best effect, reducing the sour rot, respiration rate and fruit weight loss during storage at 20 °C. HP-ß-CD-thymol increased polyphenol concentration and the activity of antioxidant enzymes, such as catalase (CAT), ascorbate peroxidase (APX) and peroxidase (POD) in lemon peel, and the highest effects were found with the 50-mM dose. In conclusion, the results show that the use of thymol encapsulated by MW into HP-ß-CD could be an effective and sustainable tool, a substitute to the synthetic fungicides, for G. citri-auriantii control in citrus fruit.

Production of volatile compounds by yeasts using hydrolysed grape seed oil obtained by immobilized lipases in continuous packed-bed reactors.

Lipases CAL-B, TLL, and RML were used in the synthesis of free fatty acids of grape seed oil as heterogeneous substrate. The best enzyme was used to optimize the reaction variables temperature, enzyme content, and molar ratio of water:oil in batch reactions using experimental planning. The ideal conditions to produce free fatty acids using pure RML were 45 °C, 12:1 substrate molar ratio, and 15% enzyme, resulting in 66% of oil hydrolysis and a productivity of 0.54 mol L-1 min-1 in 4 h of reaction at 180 rpm. Repeated batches of reaction were performed testing the operational stability of RML, results showing that this enzyme could be used for at least 20 cycles keeping more than 80% of its initial activity, suggesting its potential use in industrial processes. The synthesis of free fatty acids was then evaluated in continuous reactions using packed-bed reactor (PBR). The highest productivity in the continuous process was 6.85 mol L-1 min-1, using only RML, showing an operational stability higher than 80% of its initial conversion capacity after 11 days of operation, at a flow rate of 0.13 mL min-1 at 45 °C. We evaluated the use of this hydrolyzed oil as substrate for lactone bioproduction using Galactomyces geotrichum UFMG-CM-Y3276, G. geotrichum UFMG-CM-Y3558, and Geotrichum klebahnii UFMG-CM-Y3014 screened for their oil-hydrolysis ability. Volatile compounds were qualitatively identified in GC-MS as γ-octalactone and γ-nonalactone.

Determination of metabolites of Geotrichum citri-aurantii treated with peppermint oil using liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry.

Sour rot is a leading disease of citrus fruit caused by the postharvest pathogen Geotrichum citri-aurantii. It has been reported that essential oils can be used as substitutes for synthetic fungicides to control the pathogen. In this study, changes in metabolites and antifungal effects of G. citri-aurantii treated with peppermint oil (PO) were investigated. The inhibition rate of the mycelial growth increased as the PO concentration increased, and 6 µl PO/disk resulted in a radial growth inhibition of 79.2%. The electrical conductivity of G. citri-aurantii treated with PO increased compared to the control. By comparing the metabolic profiles of treated and untreated G. citri-aurantii cells, a total of 53 distinct metabolites 9 were up-regulated and 44 were down-regulated were found, including 16 lipid metabolites, 6 carbohydrate metabolites, 2 amino acid metabolites, 5 alcohols, 2 glycoside metabolites, and 3 ketone metabolites, etc, and these metabolites are involved in 25 major metabolic pathways. PRACTICAL APPLICATIONS: Chemical fungicides can effectively control G. citri-aurantii during fruit postharvest period. However, synthetic chemical fungicides have gradually led to buildup of resistance of fungil, which seriously causes the frequent of food-borne diseases. PO extracted from natural plants can be used as natural additive in many foods due to their antioxidant, antibacterial, and antifungal properties. Therefore, PO can be considered as a promising bacteriostatic agent for the defense of G. citri-aurantii during fruit postharvest period.

Antifungal efficiency of wild plants against human-opportunistic pathogens.

BACKGROUND: Fungal infection with opportunistic fungi can cause a serious problem for immunocompromised persons such as organ-transplant recipients, cancer, and HIV/AIDS patients. Control of these organisms using natural products is an interesting strategy to avoid the use of heavy chemotherapy in patients. OBJECTIVE: This study aimed to use the extract of Forsskaolea tenacissima L. and Xanthium spinosum L. to suppress the growth of Candida albicans and Geotrichum candidum and to investigate their potential mode of action. MATERIALS AND METHODS: Different plant extracts were tested for their antifungal activity using disc diffusion method and their mode of action was explored using the scanning electron microscopy (SEM) and gas chromatography-mass spectrometry (GC-MS). RESULTS: The results showed that chloroform extract of X. spinosum was the most effective against G. candidum, inhibiting its growth at very low concentration (38µg/mL). Chloroform extract of F. tenacissima was the most effective against C. albicans, with a minimum inhibitory concentration of 39µg/mL. SEM demonstrated the fungitoxicity of the plant extracts against both pathogens. C. albicans treated with plant extract were invaginated and ruptured and the treated mycelia of G. candidum were distorted and squashed. GC-MS analysis showed that the chloroform extract of both plants had 13 different compounds. CONCLUSION: Due to these promising results, these extracts should be further investigated and tested on different strains of C. albicans and G. candidum towards validation of their efficacy as a natural drug.

Invasive Fungal Infection Caused by Geotrichum clavatum in a Child with Acute Leukemia: First Documented Case from Mainland China.

Invasive fungal infections are one of the vital complications among acute leukemia patients undergoing induction chemotherapy. Among them, Geotrichum clavatum infections present extremely rarely with atypical clinical symptoms which make them difficult to diagnose. In this paper, we report a case of infection caused by Geotrichum clavatum in a 10-year old child with acute leukemia, which is the first documented case from mainland China. With underlying childhood leukemia, the child suffered from recurrent bacterial and fungal infection and even underwent abdominal surgery during the treatment. Fortunately, the therapeutic effect was finally achieved by adjusting the treatment program to dual anti-fungal treatment with micafungin and amphotericin B. Information regarding the epidemiological, clinical, and therapeutic features, in this case, shows significant perspectives for anti-fungal treatment for immunocompromised individuals, wherefore the rate of recovery and survival can be achieved.

Date Palm Trees Root-Derived Endophytes as Fungal Cell Factories for Diverse Bioactive Metabolites.

Endophytic fungi of healthy and brittle leaf diseased (BLD) date palm trees (Phoenix dactylifera L.) represent a promising source of bioactive compounds with biomedical, industrial, and pharmaceutical applications. The fungal endophytes Penicillium citrinum isolate TDPEF34, and Geotrichum candidum isolate TDPEF20 from healthy and BLD date palm trees, respectively, proved very effective in confrontation assays against three pathogenic bacteria, including two Gram-positive bacteria Bacillus thuringiensis (Bt) and Enterococcus faecalis (Ef), and one Gram-negative bacterium Salmonella enterica (St). They also inhibited the growth of three fungi Trichoderma sp. (Ti), Fusarium sporotrichioides (Fs), Trichoderma sp. (Ts). Additionally, their volatile organic compounds (VOCs) were shown to be in part responsible for the inhibition of Ti and Ts and could account for the full inhibition of Fs. Therefore, we have explored their potential as fungal cell factories for bioactive metabolites production. Four extracts of each endophyte were prepared using different solvent polarities, ethanol (EtOH), ethyl acetate (EtOAc), hexane (Hex), and methanol (MetOH). Both endophyte species showed varying degrees of inhibition of the bacterial and fungal pathogens according to the solvent used. These results suggest a good relationship between fungal bioactivities and their produced secondary metabolites. Targeting the discovery of potential anti-diabetic, anti-hemolysis, anti-inflammatory, anti-obesity, and cytotoxic activities, endophytic extracts showed promising results. The EtOAc extract of G. candidum displayed IC50 value comparable to the positive control diclofenac sodium in the anti-inflammatory assays. Antioxidant activity was evaluated using α,α-diphenyl-ß-picrylhydrazyl (DPPH), ß-carotene bleaching, reducing power (RP), and 2,2-azino-bis(3-ethylbenzothiazoline-6-sulphonique) (ABTS) radical scavenging assays. The findings revealed strong anti-oxidant power with an IC50 of 177.55 µg/mL for G. candidum EtOAc extract using DPPH assay, probably due to high polyphenol and flavonoid content in both fungal extracts. Finally, LC-HRMS (Liquid Chromatography­High Resolution Mass Spectrometry) and GC-MS (Gas Chromatography­Mass Spectrometry) analysis of G. candidum and P. citrinum extracts revealed an impressive arsenal of compounds with previously reported biological activities, partly explaining the obtained results. Finally, LC-HRMS analysis indicated the presence of new fungal metabolites that have never been reported, which represent good candidates to follow for the discovery of new bioactive molecules.

Breakthrough infection of Geotrichum capitatum during empirical caspofungin therapy after umbilical cord blood transplantation.

We experienced a breakthrough fungal infection caused by Geotrichum capitatum during empirical therapy with caspofungin. A 68-year-old male patient with refractory acute lymphoblastic leukemia had received umbilical cord blood transplantation after two courses of induction therapy. Empirical therapy with caspofungin was initiated 5 days before transplantation. Tacrolimus was continuously infused to prevent graft-versus-host disease. A minidose of methotrexate was intravenously administered on days 1 and 3 post-transplantation, which was changed to prednisolone from day 7 due to severe mucositis. During a recurrence of fever on day 11, blood cultures were found to be positive for a yeast-like organism, which was later confirmed by mass spectrometry to be G. capitatum. The serum levels of beta-D-glucan were elevated to 747 pg/mL. Caspofungin was switched to liposomal amphotericin B; however, radiological findings revealed pulmonary, splenic, and central nervous system involvement. Progressive renal and hepatic dysfunction subsequently developed. The patient died on day 25 post-transplantation secondary to the development of hemophagocytic syndrome and respiratory failure. We emphasize that recurrent febrile episodes, prolonged neutropenia, and underlying gastrointestinal mucosal damage require extreme caution due to the possibility of breakthrough infection caused by new fungal pathogens during empirical therapy with caspofungin.

Antifungal mechanism of sodium dehydroacetate against Geotrichum citri-aurantii.

This study investigated the potential anti-fungal mechanisms of sodium dehydroacetate (SD) against Geotrichum citri-aurantii. The results showed that the cell wall integrity of G. citri-aurantii was not affected, whereas the membrane permeability of G. citri-aurantii mycelia was visibly altered by SD. Dramatic morphological changes of the mycelia, such as loss of cytoplasm, plasmolysis, and dissolution of intracellular substances, were observed by scanning electron microscopy and transmission electron microscopy analyses, indicating that the mycelium is severely damaged by the SD treatment. Furthermore, SD apparently induced a decrease in the intracellular ATP content before 30 min of exposure. An increase in the activity of the Na+/K+-ATPase was also observed, indicating that Na+ ions might enter the cell and thus disturb the energy supply. Taken together, this study's findings suggest that the anti-fungal activity of SD against G. citri-aurantii can be attributed to the disruption of cell membrane permeability and energy metabolism.

Syntheses of Novel 4-Substituted N-(5-amino-1H-1,2,4-triazol-3-yl)pyridine-3-sulfonamide Derivatives with Potential Antifungal Activity.

Candidiasis represent a serious threat for patients with altered immune responses. Therefore, we have undertaken the synthesis of compounds comprising a pyridine-3-sulfonamide scaffold and known antifungally active 1,2,4-triazole substituents. Thus a series of novel 4-substituted N-(5-amino-1H-1,2,4-triazol-3-yl)pyridine-3-sulfonamides have been synthesized by multistep reactions starting from 4-chloropyridine-3-sulfonamide via N'-cyano-N-[(4-substitutedpyridin-3-yl)sulfonyl]carbamimidothioates which were further converted with hydrazine hydrate to the corresponding 1,2,4-triazole derivatives 26-36. The final compounds were evaluated for antifungal activity against strains of the genera Candida, Geotrichum, Rhodotorula, and Saccharomycess isolated from patients with mycosis. Many of them show greater efficacy than fluconazole, mostly towards Candida albicans and Rhodotorula mucilaginosa species, with MIC values ≤ 25 µg/mL. A docking study of the most active compounds 26, 34 and 35 was performed showing the potential mode of binding to Candida albicans lanosterol 14α-demethylase. Also in vitro cytotoxicity of selected compounds have been evaluated on the NCI-60 cell line panel.