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Scientific Reports Feb 2019L-Asparaginase (L-asparagine aminohydrolase, E.C. 3.5.1.1) has been proven to be competent in treating Acute Lymphoblastic Leukaemia (ALL), which is widely observed in...
L-Asparaginase (L-asparagine aminohydrolase, E.C. 3.5.1.1) has been proven to be competent in treating Acute Lymphoblastic Leukaemia (ALL), which is widely observed in paediatric and adult groups. Currently, clinical L-Asparaginase formulations are derived from bacterial sources such as Escherichia coli and Erwinia chrysanthemi. These formulations when administered to ALL patients lead to several immunological and hypersensitive reactions. Hence, additional purification steps are required to remove toxicity induced by the amalgamation of other enzymes like glutaminase and urease. Production of L-Asparaginase that is free of glutaminase and urease is a major area of research. In this paper, we report the screening and isolation of fungal species collected from the soil and mosses in the Schirmacher Hills, Dronning Maud Land, Antarctica, that produce L-Asparaginase free of glutaminase and urease. A total of 55 isolates were obtained from 33 environmental samples that were tested by conventional plate techniques using Phenol red and Bromothymol blue as indicators. Among the isolated fungi, 30 isolates showed L-Asparaginase free of glutaminase and urease. The L-Asparaginase producing strain Trichosporon asahii IBBLA1, which showed the highest zone index, was then optimized with a Taguchi design. Optimum enzyme activity of 20.57 U mL was obtained at a temperature of 30 °C and pH of 7.0 after 60 hours. Our work suggests that isolation of fungi from extreme environments such as Antarctica may lead to an important advancement in therapeutic applications with fewer side effects.
Topics: Agaricales; Antarctic Regions; Asparaginase; Bryophyta; DNA, Fungal; Glutaminase; Phylogeny; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Sequence Analysis, DNA; Soil Microbiology; Trichosporon; Urease
PubMed: 30723240
DOI: 10.1038/s41598-018-38094-1 -
Indian Journal of Medical Microbiology 2019Over the past four decades, there has been an increase in the number of fatal opportunistic invasive trichosporonosis cases especially in immunocompromised hosts.
INTRODUCTION
Over the past four decades, there has been an increase in the number of fatal opportunistic invasive trichosporonosis cases especially in immunocompromised hosts.
OBJECTIVE
The objective of the study is to evaluate the epidemiological, clinical details and antifungal susceptibility pattern of the patients with Trichosporon infections.
MATERIALS AND METHODS
Twenty-four clinical isolates of Trichosporon species isolated from blood, samples, pleural fluid and nail were included in this study, over a period of 12 years (2005-2016) in a tertiary hospital in North India. The isolates were characterised phenotypically and few representative isolates were sequenced also. The minimum inhibitory concentration (MIC) was determined as per Clinical and Laboratory Standards Institute, 2012.
RESULTS
Trichosporon spp. from blood culture (57.78%), nail (37.5%) and pleural fluid (4.17%). On phenotypic tests, 79.16% of the isolates were Trichosporon asahii, followed by Trichosporon dermatis (8.33%), Trichosporon japonicum (4.17%), Trichosporon ovoides (4.17%) and Trichosporon mucoides (4.17%). The MIC range of Trichosporon species from invasive infections were fluconazole (0.06-256 μg/ml), amphotericin B (0.125-16 μg/ml), voriconazole (0.0616-8 μg/ml), posaconazole (0.0616-32 μg/ml) and caspofungin (8-32 μg/ml). The isolates from superficial infection were resistant to fluconazole (0.06-256 μg/ml) and itraconazole (0.125-32 μg/ml), all were susceptible to ketoconazole and while only two were resistant to voriconazole (0.25-4 μg/ml).
CONCLUSION
T. asahii was the most common isolate. Disseminated trichosporonosis is being increasingly reported worldwide including India and represents a challenge for both diagnosis and species identification. Prognosis is limited, and antifungal regimens containing triazoles appear to be the best therapeutic approach. In addition, accurate identification, removal of central venous lines and voriconazole-based treatment along with control of underlying conditions were associated with favourable outcomes.
Topics: Antifungal Agents; Drug Resistance, Fungal; Humans; India; Microbial Sensitivity Tests; Trichosporon; Trichosporonosis
PubMed: 32436877
DOI: 10.4103/ijmm.IJMM_19_146 -
Pathogens (Basel, Switzerland) Apr 2021The microbiota of the gastrointestinal tract of humans and animals is inhabited by a diverse community of bacteria, fungi, protozoa, and viruses. In cases where there is...
The microbiota of the gastrointestinal tract of humans and animals is inhabited by a diverse community of bacteria, fungi, protozoa, and viruses. In cases where there is an imbalance in the normal microflora or an immunosuppression on the part of the host, these opportunistic microorganisms can cause severe infections. The study presented here evaluates the biochemical and antifungal susceptibility features of spp., uncommon non- strains isolated from the gastrointestinal tract of healthy turkeys. The and accounted for 7.7% of all fungi isolates. The biochemical tests showed that had active esterase (C4), esterase-lipase (C8) valine arylamidase, naphthol-AS-BI phosphohydrolase, α-galactosidase, and β-glucosidase. Likewise, demonstrated esterase-lipase (C8), lipase (C14), valine arylamidase, naphthol-AS-BI phosphohydrolase, α-galactosidase, and β-glucosidase activity. and isolated from turkeys were itraconazole resistant and amphotericin B, fluconazole, and voriconazole susceptible. Compared with human isolates, the MIC range and MIC values of turkey isolates to itraconazole were in a higher range limit in both species, while MIC values to amphotericin B, fluconazole, and voriconazole were in a lower range limit. Furthermore, the obtained ITS1-5.8rRNA-ITS2 fragment sequences were identical with and sequences isolated from humans indicating that these isolates are shared pathogens.
PubMed: 33946204
DOI: 10.3390/pathogens10050538 -
Journal of Clinical Microbiology Apr 2005Trichosporonosis is an uncommon but frequently fatal mycosis in immunocompromised patients. A multicenter retrospective study was conducted to characterize cases of... (Review)
Review
Invasive infections caused by Trichosporon species and Geotrichum capitatum in patients with hematological malignancies: a retrospective multicenter study from Italy and review of the literature.
Trichosporonosis is an uncommon but frequently fatal mycosis in immunocompromised patients. A multicenter retrospective study was conducted to characterize cases of proven or probable invasive trichosporonosis diagnosed over the past 20 years in Italian patients with hematological diseases. Of the 52 cases identified, 17 were classified as Trichosporon sp. infections and 35 were attributed to Geotrichum capitatum. Acute myeloid leukemia accounted for 65.4% of the cases. The incidence rates of Trichosporon sp. and G. capitatum infections in acute leukemia patients were 0.4 and 0.5%, respectively. Overall, 76.9% of cases had positive blood cultures. Pulmonary involvement was documented in 26.9% of cases. Death was reported for 57.1% of G. capitatum infections and for 64.7% of Trichosporon sp. infections. A literature review on trichosporonosis in patients with any underlying disease or condition reveals G. capitatum as a predominantly European pathogen, particularly in certain Mediterranean areas, while Trichosporon sp. infections are seen with similar frequencies on all continents. The majority of published Trichosporon sp. and G. capitatum infections occurred in patients with hematological diseases (62.8 and 91.7%, respectively). Well over half of these were suffering from acute leukemia (68 and 84% of patients with Trichosporon sp. and G. capitatum infections, respectively). Crude mortality rates were 77% for Trichosporon spp. and 55.7% for G. capitatum. The optimal therapy for trichosporonosis has yet to be identified; however, in vitro experiences are providing encouraging evidence of the potential role of the new triazoles, in particular, voriconazole.
Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Female; Geotrichosis; Geotrichum; Hematologic Neoplasms; Humans; Infant; Italy; Male; Middle Aged; Mycoses; Retrospective Studies; Trichosporon
PubMed: 15815003
DOI: 10.1128/JCM.43.4.1818-1828.2005 -
Frontiers in Microbiology 2016This review aimed to better depict the clinical features and address the issue of therapeutic management of deep-seated infections. We comprehensively reviewed the... (Review)
Review
This review aimed to better depict the clinical features and address the issue of therapeutic management of deep-seated infections. We comprehensively reviewed the cases of invasive infection reported in the literature from 1994 (date of taxonomic modification) to 2015. Data from antifungal susceptibility testing (AST) studies were also analyzed. Two hundred and three cases were retained and split into four groups: homeopathy ( = 79), other immunodeficiency conditions ( = 41), miscellaneous ( = 58) and newborns ( = 25). was the main causative species (46.7%) and may exhibit cross-resistance to different antifungal classes. The unfavorable outcome rate was at 44.3%. By multivariate analysis, breakthrough infection (OR 2.45) was associated with unfavorable outcome, whilst the use of an azole-based therapy improved the prognosis (OR 0.16). Voriconazole-based treatment was associated with favorable outcome in hematological patients (73.6 vs. 41.8%; = 0.016). Compiled data from AST demonstrated that (i) exhibits the highest MICs to amphotericin B and (ii) voriconazole has the best efficacy against clinical isolates of spp. infection is not only restricted to hematological patients. Analysis of compiled data from AST and clinical outcome support the use of voriconazole as first line therapy.
PubMed: 27799926
DOI: 10.3389/fmicb.2016.01629 -
Microorganisms Nov 2023is a basidiomycete yeast that is pathogenic to humans and animals, and fluconazole-resistant strains have recently increased. Farnesol secreted by fungi is a factor...
is a basidiomycete yeast that is pathogenic to humans and animals, and fluconazole-resistant strains have recently increased. Farnesol secreted by fungi is a factor that causes variations in fluconazole resistance; however, few studies have explored the underlying mechanisms. Therefore, this study aims to delineate the fluconazole resistance mechanisms of and explore farnesol's effects on these processes. A comparative metabolome-transcriptome analysis of untreated fluconazole-sensitive (YAN), fluconazole-resistant (PB) strains, and 25 μM farnesol-treated strains (YAN-25 and PB-25, respectively) was performed. The membrane lipid-related genes and metabolites were upregulated in the PB vs. YAN and PB-25 vs. PB comparisons. Farnesol demonstrated strain-dependent mechanisms underlying fluconazole tolerance between the YAN and PB strains, and upregulated and downregulated efflux pumps in PB-25 and YAN-25 strains, respectively. Membrane lipid-related metabolites were highly correlated with transporter-coding genes. Fluconazole resistance in was induced by membrane lipid bio-synthesis activation. Farnesol inhibited fluconazole resistance in the sensitive strain, but enhanced resistance in the resistant strain by upregulating efflux pump genes and membrane lipids. This study offers valuable insights into the mechanisms underlying fungal drug resistance and provides guidance for future research aimed at developing more potent antifungal drugs for clinical use.
PubMed: 38004810
DOI: 10.3390/microorganisms11112798 -
BMC Microbiology May 2019Trichosporon is the dominant genus of epidermal fungi in giant pandas (Ailuropoda melanoleuca) and causes local and deep infections. To provide the information needed... (Comparative Study)
Comparative Study
BACKGROUND
Trichosporon is the dominant genus of epidermal fungi in giant pandas (Ailuropoda melanoleuca) and causes local and deep infections. To provide the information needed for the diagnosis and treatment of trichosporosis in giant pandas, the sequence of ITS, D1/D2, and IGS1 loci in 29 isolates of Trichosporon spp. which were isolated from the body surface of giant pandas were combination to investigate interspecies identification and genotype. Morphological development was examined via slide culture. Additionally, mice were infected by skin inunction, intraperitoneal injection, and subcutaneous injection for evaluation of pathogenicity.
RESULTS
The twenty-nine isolates of Trichosporon spp. were identified as 11 species, and Trichosporon jirovecii and T. asteroides were the commonest species. Four strains of T. laibachii and one strain of T. moniliiforme were found to be of novel genotypes, and T. jirovecii was identified to be genotype 1. T. asteroides had the same genotype which involved in disseminated trichosporosis. The morphological development processes of the Trichosporon spp. were clearly different, especially in the processes of single-spore development. Pathogenicity studies showed that 7 species damaged the liver and skin in mice, and their pathogenicity was stronger than other 4 species. T. asteroides had the strongest pathogenicity and might provoke invasive infection. The pathological characteristics of liver and skin infections caused by different Trichosporon spp. were similar.
CONCLUSIONS
Multiple species of Trichosporon were identified on the skin surface of giant panda, which varied in morphological development and pathogenicity. Combination of ITS, D1/D2, and IGS1 loci analysis, and morphological development process can effectively identify the genotype of Trichosporon spp.
Topics: Animals; DNA, Fungal; Female; Genotyping Techniques; Liver; Male; Mice; Phylogeny; Skin; Species Specificity; Trichosporon; Trichosporonosis; Ursidae
PubMed: 31138125
DOI: 10.1186/s12866-019-1486-7 -
Chemico-biological Interactions Sep 2021Ochratoxin A (OTA), an important fungal metabolite in foods and feeds has been shown to induce oxidative stress and cellular injuries to human and animal subjects. This...
Ochratoxin A (OTA), an important fungal metabolite in foods and feeds has been shown to induce oxidative stress and cellular injuries to human and animal subjects. This study was designed to investigate the mode of action of a biological modifier Trichosporon mycotoxinivorans (TM), against OTA-mediated oxidative stress and tissue toxicity on broiler chickens. The birds were offered diets supplemented with OTA (0.15 and 0.3 mg/kg feed) and/or TM (0.5, 1.0 g/kg) for 42 days of age, and blood and tissue samples were collected to examine the oxidative stress, biochemical and histopathological parameters. Dietary OTA at all the tested levels induced the hepatic and renal tissue injury as indicated by significant decreased total antioxidant capacity in these organs along with significant decreased (p ≤ 0.05) serum concentrations of total proteins and albumin. The serum concentrations of alanine aminotransferase (ALT) and urea were significantly increased, and these observations were further supported by degenerative changes and increased relative weights of liver and kidneys. The dietary supplementation of TM at both tested levels relieved the detrimental impact of 0.15 and 0.3 mg OTA/kg on the studied parameters. The results of the study demonstrated that dietary TM significantly protects broiler chickens by reducing OTA-induced oxidative damage and tissue injury.
Topics: Animals; Aspergillus ochraceus; Basidiomycota; Chemical and Drug Induced Liver Injury; Chickens; Dietary Supplements; Kidney; Kidney Diseases; Liver; Mycotoxins; Ochratoxins; Organ Size; Oxidative Stress; Trichosporon
PubMed: 34364835
DOI: 10.1016/j.cbi.2021.109614 -
Frontiers in Microbiology 2022Melanin is one of the most studied virulence factors in pathogenic fungi. This pigment protects them from a series of both environmental and host stressors. Among...
Melanin is one of the most studied virulence factors in pathogenic fungi. This pigment protects them from a series of both environmental and host stressors. Among basidiomycetes, and are known to produce melanin in the presence of phenolic precursors. Other species from the Trichosporonaceae family also produce this pigment, but the extent to this production among the clinically relevant species is unknown. For this reason, the aim of this study was to verify the production of melanin by different Trichosporonaceae species of clinical interest and to compare their pigments with the ones from and , which are more prevalent in human infections. Melanin was produced in a minimal medium supplemented with 1 mM L-dihydroxyphenylalanine (L-DOPA). Pigment was evaluated using scanning electron microscopy, Zeta potential measurements, and energy-dispersive X-ray spectroscopy. It was found that, besides and , , , , , , and also produce melanin-like particles in the presence of L-DOPA. Melanin particles have negative charge and are smaller than original cells. Variations in color, fluorescence, and chemical composition was noticed between the studied strains. All melanins presented carbon, oxygen, sodium, and potassium in their composition. Melanins from the most pathogenic species also presented iron, zinc, and copper, which are important during parasitism. Biophysical properties of these melanins can confer to the Trichosporonaceae adaptive advantages to both parasitic and environmental conditions of fungal growth.
PubMed: 35547117
DOI: 10.3389/fmicb.2022.876611 -
Medical Mycology Journal 2015Most cases of deep-seated trichosporonosis develop in patients with neutropenia, but it has recently been reported that breakthrough infections with Trichosporon species... (Review)
Review
Most cases of deep-seated trichosporonosis develop in patients with neutropenia, but it has recently been reported that breakthrough infections with Trichosporon species can develop during the use of candin family of antifungal agents. This is due to the primary resistance of the causal fungus, Trichosporon asahii (T. asahii), to the candin agents. On the other hand, there has been a case report of infection with Trichosporon that presented high-level resistance to the azole family of antifungal agents. Therefore, the possibility that the frequent use of azole agents may lead to secondary resistance to these agents is a cause for concern. Since trichosporonosis is a relatively rare infectious disease, there has been no established breakpoint for this fungus to various antifungal agents, wherein we cannot precisely confirm its sensitivity or resistance to the agents. However, our experiment demonstrated one of the processes for acquired drug resistance, wherein the minimal inhibitory concentration of fluconazole for T. asahii was markedly elevated after its long-term in vitro exposure to the drug. Although the mechanisms for drug-resistance of Trichosporon species are unknown, it is supposed that they are the same as the mechanisms found in Candida and Aspergillus species, namely, modification of target molecules or decrease of access to the molecules. Since cases of trichosporonosis are likely to increase in the future, we believe that there is an urgent need to establish the breakpoint for T. asahii based on large-scale drug sensitivity tests, as well as to elucidate its drug-resistance mechanisms.
Topics: Antifungal Agents; Azoles; Drug Resistance, Fungal; Fluconazole; Microbial Sensitivity Tests; Neutropenia; Trichosporon; Trichosporonosis
PubMed: 26617108
DOI: 10.3314/mmj.56.J123