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Invasive mucormycosis (IM) is associated with high mortality and morbidity. MAT2203 is an orally administered lipid nanocrystal formulation of amphotericin B, which has been shown to be safe and effective against other fungal infections. We sought to compare the efficacy of MAT2203 to liposomal amphotericin B (LAMB) treatment in a neutropenic mouse model of IM due to Rhizopus arrhizus var. delemar or Mucor circinelloides f. jenssenii DI15-131. In R. arrhizus var. delemar-infected mice, 15 mg/kg of MAT2203 qd was as effective as 10 mg/kg of LAMB in prolonging median survival time vs placebo (13.5 and 16.5 days for MAT2203 and LAMB, respectively, vs 9 days for placebo) and enhancing overall survival vs placebo-treated mice (40% and 45% for MAT2203 and LAMB, respectively, vs 0% for placebo). A higher dose of 45 mg/kg of MAT2203 was not well tolerated by mice and showed no benefit over placebo. Similar results were obtained with mice infected with M. circinelloides. Furthermore, while both MAT2203 and LAMB treatment resulted in a significant reduction of ~1.0-2.0log and ~2.0-2.5log in Rhizopus delemar or M. circinelloides lung and brain burden vs placebo mice, respectively, LAMB significantly reduced tissue fungal burden in mice infected with R. delemar vs tissues of mice treated with MAT2203. These results support continued investigation and development of MAT2203 as a novel and oral formulation of amphotericin for the treatment of mucormycosis.

Ibrexafungerp (formerly SCY-078) is the first member of the triterpenoid class that prevents the synthesis of the fungal cell wall polymer β-(1,3)-D-glucan by inhibiting the enzyme glucan synthase. We evaluated the in vivo efficacy of ibrexafungerp against pulmonary mucormycosis using an established murine model. Neutropenic mice were intratracheally infected with either Rhizopus delemar or Mucor circinelloides. Treatment with placebo (diluent control), ibrexafungerp (30 mg/kg, PO BID), liposomal amphotericin B (LAMB 10 mg/kg IV QD), posaconazole (PSC 30 mg/kg PO QD), or a combination of ibrexafungerp plus LAMB or ibrexafungerp plus PSC began 16 h post-infection and continued for 7 days for ibrexafungerp or PSC and through day 4 for LAMB. Ibrexafungerp was as effective as LAMB or PSC in prolonging median survival (range: 15 days to >21 days) and enhancing overall survival (30%-65%) vs placebo (9 days and 0%; P < 0.001) in mice infected with R. delemar. Furthermore, median survival and overall percent survival resulting from the combination of ibrexafungerp plus LAMB were significantly greater compared to all monotherapies (P ≤ 0.03). Similar survival results were observed in mice infected with M. circinelloides. Monotherapies also reduce the lung and brain fungal burden by ~0.5-1.0log10 conidial equivalents (CE)/g of tissue vs placebo in mice infected with R. delemar (P < 0.05), while a combination of ibrexafungerp plus LAMB lowered the fungal burden by ~0.5-1.5log10 CE/g compared to placebo or any of the monotherapy groups (P < 0.03). These results are promising and warrant continued investigation of ibrexafungerp as a novel treatment option against mucormycosis.

Most fungal bone and joint infections (arthritis) are caused by Mucormycosis (Mucor indicus). These infections may be difficult to treat and may lead to chronic bone disorders and disabilities, thus the use of new antifungal materials in bone disorders is vital, particularly in immunocompromised individuals, such as those who have contracted coronavirus disease 2019 (COVID-19). Herein, we reported for the first time the preparation of nitrogen-doped carbon quantum dots (N/CQDs) and a nitrogen-doped mesoporous carbon (N/MC) using a quick micro-wave preparation and hydrothermal approach. The structure and morphology were analysed using X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM) and surface area analyser. Minimum inhibitory concentration (MIC), disc diffusion tests, minimum fungicidal concentration (MFC) and antifungal inhibitory percentages were measured to investigate the antifungal activity of N/CQDs and N/MC nanostructures. In addition to the in vivo antifungal activity in rats as determined by wound induction and infection, pathogen count and histological studies were also performed. According to in vitro and in vivo testing, both N/CQDs with small size and N/MC with porous structure had a significant antifungal impact on a variety of bone-infecting bacteria, including Mucor infection. In conclusion, the present investigation demonstrates that functional N/CQDs and N/MC are effective antifungal agents against a range of microbial pathogenic bone disorders in immunocompromised individuals, with stronger and superior fungicidal activity for N/CQDs than N/MC in vitro and in vivo studies. [ABSTRACT FROM AUTHOR]

Strawberries are susceptible to decay and destruction while being harvested and stored. This study had the following objectives: (1) the documentation of fungi and mycotoxin production associated with infected strawberry fruits; (2) the evaluation of the primary phytochemicals of Sargassum cinereum and Padina boergesenii by gas chromatography–mass spectrometry (GC–MS) and Fourier transform infrared (FT-IR) analysis to identify the active chemical composition of the seaweed extracts; and (3) the assessment of the antifungal activity of five extracts from brown seaweeds both in vitro and in vivo against fungal infections on fresh fruit under post-harvest conditions. The most common fungi were Aspergillus niger 14.36%, Botrytis cinerea 38.29%, and Mucor irregularis 16.88%. Padina boergesenii acetone extract had the highest in vitro antifungal activity. The methanol extracts of both S. cinereum and P. boergesenii were effective against the pathogenicity and aggressiveness (in vivo) on post-harvest strawberry fruits. B. cinerea could produce botrydial and dihydrobotrydial toxins with concentrations of 8.14 µg/mL and 4.26 µg/mL, respectively. A. niger could produce ochratoxin A with a concentration of 10.05 µg/mL. The present study demonstrates that the extracts of macroalgae S. cinereum and P. boergesenii contain secondary metabolites and antioxidants, indicating their potential utilization in antifungal applications. [ABSTRACT FROM AUTHOR]

Most fungal bone and joint infections (arthritis) are caused by Mucormycosis (Mucor indicus). These infections may be difficult to treat and may lead to chronic bone disorders and disabilities, thus the use of new antifungal materials in bone disorders is vital, particularly in immunocompromised individuals, such as those who have contracted coronavirus disease 2019 (COVID-19). Herein, we reported for the first time the preparation of nitrogen-doped carbon quantum dots (N/CQDs) and a nitrogen-doped mesoporous carbon (N/MC) using a quick micro-wave preparation and hydrothermal approach. The structure and morphology were analysed using X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM) and surface area analyser. Minimum inhibitory concentration (MIC), disc diffusion tests, minimum fungicidal concentration (MFC) and antifungal inhibitory percentages were measured to investigate the antifungal activity of N/CQDs and N/MC nanostructures. In addition to the in vivo antifungal activity in rats as determined by wound induction and infection, pathogen count and histological studies were also performed. According to in vitro and in vivo testing, both N/CQDs with small size and N/MC with porous structure had a significant antifungal impact on a variety of bone-infecting bacteria, including Mucor infection. In conclusion, the present investigation demonstrates that functional N/CQDs and N/MC are effective antifungal agents against a range of microbial pathogenic bone disorders in immunocompromised individuals, with stronger and superior fungicidal activity for N/CQDs than N/MC in vitro and in vivo studies.

Mucormycosis is a fungal infection that mostly occurs in immunocompromised patients. Other risk factors are diabetes mellitus, solid organ transplant, and long use of glucocorticoids. Early diagnosis and treatment should be made due to the fierce behavior of this infection and the high chances of dissemination. Here, we present a case of pulmonary mucormycosis in a diabetic and hypertensive patient who had a renal transplant and presented with cough, hemoptysis, and shortness of breath. After all investigation, he was diagnosed with pulmonary mucormycosis and treated with antifungal drugs. The patient died due to the aggressive nature of infection and renal failure.

Introduction: Mucormycosis is an acute onset, invasive, fungal infection, characterized by organ involvement, and caused by Mucor, Rhizopus, or Absidia. Our aim was to present a case of mucormycotic infection and emphasize its importance in a diabetic immunosuppressed patient with acute myeloid leukemia (AML). Case presentation: A 68-year-old hypertensive and diabetic male patient with a diagnosis of AML developed respiratory failure and exhibited diffuse bilateral consolidation in high-resolution computed tomography (HRCT). The treatment plan involved chemotherapy with cytarabine (200 mg/m2/day for 7 days) and daunorubicin (60 mg/m2/day for 3 days) starting on 20 July 2022. Posaconazole prophylactic treatment was initiated on 23 July 2022, to prevent fungal infections. Five days later there was a black necrotic appearance on the left wing of the nose. The patient underwent excision of the left wing of the nose. Mucor was detected in the excision tissue both histopathologically and in culture. A culture under lactophenol cotton blue (LFCB) staining displaying hyphal structures of Mucor was obtained. The patient died of progressive pneumonia and sepsis. Conclusions: Mucormycosis is an infection with high mortality, and should be considered in the early stages of diagnosis when dealing with immunosuppression patients. [ABSTRACT FROM AUTHOR]

Background: Chitosan oligosaccharides (COS) have great potential for applications in several fields, including agriculture, food industry or medicine. Nevertheless, the large-scale use of COS requires the development of cost-effective technologies for their production. The main objective of our investigation was to develop an effective method of enzymatic degradation of chitosan in a column reactor using Mucor circinelloides IBT-83 cells, immobilized in a polyurethane foam (PUF). These cells serve as a source of chitosanolytic enzymes. Results: The study revealed that the process of freeze-drying of immobilized mycelium increases the stability of the associated enzymes during chitosan hydrolysis. The use of stabilized preparations as an active reactor bed enables the production of COS at a constant level for 16 reactor cycles (384 h in total), i.e. 216 h longer compared to non-stabilized mycelium. In the hydrolysate, oligomers ranging in structure from dimer to hexamer as well as D-glucosamine were detected. The potential application of the obtained product in agriculture has been verified. The results of phytotests have demonstrated that the introduction of COS into the soil at a concentration of 0.01 or 0.05% w/w resulted in an increase in the growth of Lepidium sativum stem and root, respectively (extensions by 38 and 44% compared to the control sample). Conclusions: The research has verified that the PUF-immobilized M. circinelloides IBT-83 mycelium, which has been stabilized through freeze-drying, is a promising biocatalyst for the environmentally friendly and efficient generation of COS. This biocatalyst has the potential to be used in fertilizers. [ABSTRACT FROM AUTHOR]

The current investigation involved the isolation of 13 endophytic fungi from Taxus sp. collected in Himachal Pradesh, India. Among these, isolate PAT-3 produced 195.13 mg/L of Taxol in reformative medium broth using microbial fermentation as an alternative source. The PAT-3 isolate was characterized as Mucor circinelloides through morphologic and molecular techniques. The PAT-3 isolate was the only one to exhibit positive results for the Taxol biosynthesis-related genes 10-deacetylbaccatin-III-10-O-acetyltransferase (dbat), Baccatin-III, 3: amino, 3 phenylpropanol transferase (bapt), and taxadienol-acetyltransferase (tat). Furthermore, human breast cancer (MCF-7) and human melanoma cancer (SKMEL-28) cell lines demonstrated the cytotoxicity of Taxol extracted from isolate PAT-3, with IC50 values of 80.32 µg/mL and 77.21 µg/mL, respectively. To our knowledge, this is the first study that demonstrates the ability of the endophytic fungus M. circinelloides from Taxus sp. in the northern Himalayan region to produce paclitaxel. The study's findings show that Mucor circinelloides is an excellent alternative source of Taxol, and they may pave the way for the production of Taxol at the industrial level in future. [ABSTRACT FROM AUTHOR]

Rice wine (RW) and its fermentation residue, rice wine lees (RWL), are prepared using a traditional starter culture (TSC). The TSC contains a combination of different fungal and bacterial species that are variable in composition. This study evaluated the effects on the nutritional profile and the sensory qualities of RWL using various combinations of these fungal species as starter cultures. We isolated the three most abundant fungal species in TSC and found them to be Rhizopus oryzae (RO), Mucor indicus (MI), and Saccharomyces cerevisiae (SC). Although sensory evaluation revealed that the RWL produced using the RO+SC was the most preferred (n = 30) in color, aroma, sweetness, bitterness, and clarity, no significant differences were observed compared to when RO+MI+SC was used. Moreover, the RO+MI+SC-produced rice wine lees demonstrated the highest nutritional composition in terms of the following: crude protein content (11.12±0.08%), total energy (412.96±0.07 kcal/100 g), essential amino acids, and vitamin content. Hence, the combination of these three fungal species, RO, MI, and SC, as a starter culture in rice wine fermentation gives rise to rice wine lees with higher nutritional value than using the traditional rice wine starter culture. [ABSTRACT FROM AUTHOR]

Previously, we constructed engineered M. circinelloides strains that can not only utilize cellulose, but also increase the yield of γ-linolenic acid (GLA). In the present study, an in-depth analysis of lipid accumulation by engineered M. circinelloides strains using corn straw was to be explored. When a two-stage temperature control strategy was adopted with adding 1.5% cellulase and 15% inoculum, the engineered strains led to increases in the lipid yield (up to 1.56 g per 100 g dry medium) and GLA yield (up to 274 mg per 100 g dry medium) of 1.8- and 2.3-fold, respectively, compared with the control strain. This study proved the engineered M. circinelloides strains, especially for Mc-C2PD6, possess advantages in using corn straw to produce GLA. This work provided a reference for transformation from agricultural cellulosic waste to functional lipid in one step, which might play a positive role in promoting the sustainable development of biological industry. [ABSTRACT FROM AUTHOR]

ABSTRACT: Background: During the coronavirus disease 2019 (COVD-19) pandemic, the incidence of mucormycosis also increased, especially affecting individuals who have had the COVID-19 infection in the past. Aims: The aim of the study is to assess risk factors and clinical and histopathological features of mucormycosis in post-COVID-19 cases. Methods: This is a retrospective study conducted in a tertiary care COVID-19-dedicated hospital, Dehradun, Uttarakhand, India, over a period of 2 months during the COVID-19 pandemic. All surgical specimens submitted for histopathology with a suspected diagnosis of mucormycosis were included. Histopathology was considered the gold standard. All histopathologically confirmed cases were studied in detail with respect to histopathology, clinico-radiological features, and microbiological results Results: Of 25 cases with clinical diagnosis of mucormycosis, nine were histopathologically confirmed as mucormycosis. Seven patients had diabetes, while two did not have any co-morbidity. The fungal load was heavy in 50% cases, and the proportion of necrosis was higher with diabetes mellitus, as compared to non-diabetic and non-co-morbidity patients. Angioinvasion (33.3% cases), soft-tissue invasion (44.4%), Splendor–Hoeppli phenomenon (44.4%), and neural invasion (11.1%) were also present. Mixed infection (Mucormycosis and Aspergillus species) was present in three of the cases who also had diabetes. The microbiological investigations were positive in only 55.5% cases. Conclusion: Post-COVID Mucormycosis has fatal outcomes. Early diagnosis and treatment are the key to successful treatment. Early and reliable diagnosis can be offered by histopathological examination. [ABSTRACT FROM AUTHOR]

Background: Acute invasive fungal rhinosinusitis (AIFRS) is a severe infection that affects the nasal cavity and paranasal sinuses, often seen in individuals with comorbidities such as diabetes mellitus and hemato-oncological diseases. This study aims to retrospectively analyze patients diagnosed with AIFRS from 2014 to 2023. Methods: The study was a single-center, descriptive investigation focusing on demographic details, clinical presentation, radio-pathological features, and suggested management of AIFRS patients. Results: Of the 25 patients involved in the study, with a mean age of 48 years, hematooncological diseases were the most common underlying condition (44%), followed by diabetes mellitus (28%). Fungal analysis revealed Aspergillus species (32%) and Mucor (24%). The most frequently involved site was the middle turbinate (84%), while the least affected was the inferior turbinate (36%). The mortality rate was 48%, primarily due to underlying hemato-oncological diseases (32%). Aspergillus (16%) and Mucor (16%) were the most commonly encountered pathogens in fatal cases. Conclusion: Patients with diabetes mellitus, hemato-oncological diseases, or secondary immunodefciency undergoing steroid treatment should be vigilantly screened for AIFRS. Early diagnosis and prompt management are crucial to improve patient outcomes. [ABSTRACT FROM AUTHOR]

To study the mechanisms of protection of the cell membranes and macromolecules from cold, the composition of osmolytes, membrane lipids, and their fatty acids in a submerged culture of Mucor flavus was analyzed in growth dynamics at 20 and 4°C. This micromycete is psychrotolerant, having a wide growth temperature range (from –2 to 25°C) with an optimum at 20°C. Mucor flavus has a high growth rate (15 mm/day at 20°C, 4 mm/day at 0°C). At both temperatures, phosphatidic acids and phosphatidylethanolamines were predominant in the composition of membrane lipids, while phosphatidylcholines were the minor components. The main difference in the composition of membrane lipids was the threefold lower share of sterols at 4°C. During growth under optimal conditions, the proportion of phosphatidic acids decreased against the background of a slight increase in the levels of sterols, phosphatidylethanolamines, and phosphatidylcholines, while at 4°C the proportion of phosphatidic acids decreased slightly and the proportion of phosphatidylcholines increased. The fatty acids composition of phospholipids during growth at 20°C did not change significantly; linoleic, oleic, linolenic, and palmitic acids were predominant. At 4°C, the proportion of palmitic acid decreased and that of oleic acid increased, while the proportion of γ-linolenic acid decreased by half while that of α-linoleic acid increased. However, these changes did not lead to a significant change in the unsaturation degree of phospholipids, which varied between 1.5 and 1.6. Trehalose and glucose were the predominant osmolytes of the cytosol; glycerol was present in minor amounts only at 4°C. At both temperatures, the amount of osmolytes reached 3% of the dry weight in the course of growth, and the proportion of trehalose reached 70%. At both temperatures, a constant composition of osmolytes and slight changes in the composition of membrane lipids and their degree of unsaturation were observed, which probably contributes to the high growth rate of the fungus over a wide temperature range. [ABSTRACT FROM AUTHOR]

Thrombosis is a dangerous condition that can result in major damage. Fibrinolytic enzymes are significant therapeutic agents for thrombosis. This study focused on MsFE, a fibrinolytic protease from M. subtilissimus UCP1262, exploring its physicochemical traits and the impact of gamma radiation on its activity. Investigations included: fibrinogenolytic activity, effects of solvents and ions, gamma rays, enzyme shelf life, FTIR, CD, clotted times determination, and enzymatic kinetics. Notably, the major results obtained show the protease retained 90 % activity in organic solvents, FTIR indicated carbonyl functional groups and Circular dichroism spectroscopic studies indicated that the secondary structure (β-sheet) of enzyme remains mostly unaffected over pH 2.0–9.0, whereas considerable changes were observed in the tertiary structure. Kinetic analysis revealed altered parameters post-irradiation. Gamma radiation initially enhanced enzyme activity (10 kGy) but progressively decreased beyond 20 kGy. Metallic ions, especially magnesium, augmented irradiated enzyme activity. This study highlights gamma radiation's potential as a modulator for enhanced fibrinolytic activity, suggesting future biomedical applications. [Display omitted] • Mucor subtilissimus proves its significance as a producer of fibrinolytic proteases. • The protease degrades the α, β and γ chains of fibrinogen. • The 10 kGy radiation increased the activity of the enzyme by approximately 10 %. • Fe2+, Cu2+ and Mg2+ were able to increase the activity of the irradiated enzyme. • Produced enzymes can be a highly productive fibrinolytic for medical applications. [ABSTRACT FROM AUTHOR]

In this study, Cydia pomonella (Linnaeus, 1758) entomopathogenic microorganisms were isolated from damaged insect carcasses in the territory of Tashkent and Fergana regions of Uzbekistan. Insect specimens were selected using the trapping belt method and 30 strains of micromycetes were isolated from these specimens. In morphological and cultural studies, entomopathogenic micromycetes in dead and infected individuals of C. romonella belong to the genera Penicillium, Aspergillus, Fusarium, Alternaria. The results obtained showed that micromycetes of the species Penicillium chrysogenum Thom, Alternaria alternata (Fr.) Keissl., Fusarium solani (Mart.) Sacc., Fusarium oxysporum Schltdl., Aspergillus fumigatus Fresen., Aspergillus niger Tiegh., Aspergillus terreus Thom were present both in the suspension after washing off the insects and in the homogenized insects.

Background: Bowel mucormycosis is common among high-risk surgical neonates and has high fatality. This study was done to study the clinical profile and outcome of pediatric surgical patients operated at our center who had bowel mucormycosis on histology. Methods: It was a retrospective observational study. The data was collected from the medical records department. The files of surgical patients with tissue diagnosis of bowel mucormycosis operated at Chacha Nehru Bal Chikitsalaya from June 2018 to May 2021 were retrieved. The data was tabulated on Microsoft Excel sheet®. Results: A total of 11 surgical patients with bowel mucormycosis on histology were traced. The study had male preponderance. The majority were neonates and had low platelet counts with raised CRP levels. All but one expired, with severe sepsis and septic shock as major causes of death. Conclusion: The invasive mucormycosis is more common among neonates (but older children are not immune) with male preponderance. It may affect any part of GIT and the counts and sepsis screen may be normal. It has a high fatality rate.

Background: During the coronavirus disease 2019 (COVD-19) pandemic, the incidence of mucormycosis also increased, especially affecting individuals who have had the COVID-19 infection in the past. Aims: The aim of the study is to assess risk factors and clinical and histopathological features of mucormycosis in post-COVID-19 cases. Methods: This is a retrospective study conducted in a tertiary care COVID-19-dedicated hospital, Dehradun, Uttarakhand, India, over a period of 2 months during the COVID-19 pandemic. All surgical specimens submitted for histopathology with a suspected diagnosis of mucormycosis were included. Histopathology was considered the gold standard. All histopathologically confirmed cases were studied in detail with respect to histopathology, clinico-radiological features, and microbiological results Results: Of 25 cases with clinical diagnosis of mucormycosis, nine were histopathologically confirmed as mucormycosis. Seven patients had diabetes, while two did not have any co-morbidity. The fungal load was heavy in 50% cases, and the proportion of necrosis was higher with diabetes mellitus, as compared to non-diabetic and non-co-morbidity patients. Angioinvasion (33.3% cases), soft-tissue invasion (44.4%), Splendor–Hoeppli phenomenon (44.4%), and neural invasion (11.1%) were also present. Mixed infection (Mucormycosis and Aspergillus species) was present in three of the cases who also had diabetes. The microbiological investigations were positive in only 55.5% cases. Conclusion: Post-COVID Mucormycosis has fatal outcomes. Early diagnosis and treatment are the key to successful treatment. Early and reliable diagnosis can be offered by histopathological examination.

The incidence of colon perforation in the posttransplant period is 1.3% based on various single-center studies. We report the case of a 32-year-old male, a known case of chronic kidney disease and end-stage renal disease who received a live-related ABO-compatible transplant. The patient was started on tacrolimus, mycophenolate mofetil, and steroids; no induction was given. The patient had a delayed graft function, and his creatinine was persistently high. Hence, a biopsy was done on postoperative day 4, which revealed an acute tubular injury with features of calcineurin inhibitor toxicity. His tacrolimus dose was reduced and his output improved until day 13, after which his renal function worsened. The repeat tacrolimus level was low. Hence, the patient was started on pulse steroids and discharged after the patient improved symptomatically (discharge creatinine: 2.1). The patient was readmitted 3 days after discharge with severe abdominal pain. The patient’s blood pressure was 90/30 mmHg; he was drowsy and tachypneic. His abdomen was distended. Computed tomography of the abdomen revealed pneumoperitoneum, and the patient was subjected to an explorative laparotomy. There was colonic perforation. The peritoneum and colon revealed multiple punched-out lesions and a right hemicolectomy was done. A biopsy revealed suppurative inflammation involving all three layers with multiple giant cells, and tissue staining revealed ribbon-like aseptate hyphae with 90° angulation suggestive of mucormycosis. The patient expired in the immediate postoperative period. The final diagnosis of mucormycosis-associated colon perforation was made. Only one such case has been reported previously.

Mucormycosis is an invasive fungal infection caused by certain members of the fungal order of Mucorales. The species most frequently identified as the etiological agents of mucormycosis belong to the genera Rhizopus, Lichtheimia, and Mucor. The frequency of systemic mucormycosis has been increasing, mainly because of increasing numbers of susceptible patients. Furthermore, Mucorales display intrinsic resistance to the majority of routinely used antifungal agents (e.g., echinocandins and short-tailed azoles), which limits the number of possible therapeutic options. All the above-mentioned issues urge the improvement of molecular identification methods and the discovery of new antifungal targets and strategies. Spore coat proteins (CotH) constitute a kinase family present in many pathogenic bacteria and fungi and participate in the spore formation in these organisms. Moreover, some of them can act as virulence factors being receptors of the human GRP78 protein during Rhizopus delemar-induced mucormycosis. We identified 17 cotH-like genes in the Mucor lusitanicus genome database. Successful disruption of five cotH genes in Mucor was performed using the CRISPR-Cas9 system. The CotH3 and CotH4 proteins play a role in adaptation to different temperatures as well as in developing the cell wall structure. We also show CotH4 protein is involved in spore wall formation by affecting the total chitin content and, thus, the composition of the spore wall. The role of CotH3 and CotH4 proteins in virulence was confirmed in two invertebrate models and a diabetic ketoacidosis (DKA) mouse model. IMPORTANCE Current treatment options for mucormycosis are inadequate, resulting in high mortality rates, especially among immunosuppressed patients. The development of novel therapies for mucormycosis has been hampered by lack of understanding of the pathogenetic mechanisms. The importance of the cell surface CotH proteins in the pathogenesis of Rhizopus-mediated mucormycosis has been recently described. However, the contribution of this family of proteins to the virulence of other mucoralean fungi and their functionality in vital processes remain undefined. Through the use of the CRISPR-Case9 gene disruption system, we demonstrate the importance of several of the CotH proteins to the virulence of Mucor lusitanicus by using three infection models. We also report on the importance of one of these proteins, CotH4, to spore wall formation by affecting chitin content. Therefore, our studies extend the importance of CotH proteins to Mucor and identify the mechanism by which one of the CotH proteins contributes to the development of a normal fungal cell wall, thereby indicating that this family of proteins can be targeted for future development of novel therapeutic strategies of mucormycosis.

Introduction: The severe acute respiratory syndrome coronavirus 2 that is the cause of the coronavirus disease-2019 (COVID-19) pandemic is linked to a variety of opportunistic bacterial and fungal coinfections. Orofacial mycoses, fungal infections affecting the oral and facial regions, have recently gained attention as potential complications in individuals with COVID-19. Materials and Methods: This study aims to contribute to the understanding of orofacial mucormycosis in the context of COVID-19, particularly focusing on the prevalence among patients in a tertiary care center in Northern India. This study comprised respiratory materials from 255 COVID-19 patients treated at Max Hospital, Saket. The laboratory received specimens for microbiological pneumonia workup culture and molecular detection. Results: The most prevalent site for mucormycosis was the rhino-orbital region, accounting for a majority of cases at 58.2%. Following the rhino-orbital region, the involvement extended to the rhino-orbital-cerebral region in a notable proportion of cases. Pulmonary sites were identified as a significant location for mucormycosis, though less frequent compared to the rhino-orbital region. Mucormycosis diagnoses were predominantly made using direct microscopy, with 82.6% (196/255) of patients undergoing this diagnostic method. Conclusion: Our study in Northern India revealed a high prevalence of orofacial mucormycosis in middle-aged diabetic males, often with a history of COVID-19 hospitalization and steroid use. Rhizopus spp. were the most common Mucorales identified, with treatment challenges due to antifungal resistance. Molecular tests, such as matrix-assisted laser desorption ionization–time of flight, are valuable for species identification, emphasizing the need for heightened awareness during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Fungi, including filamentous fungi and yeasts, are major contributors to global food losses and waste due to their ability to colonize a very large diversity of food raw materials and processed foods throughout the food chain. In addition, numerous fungal species are mycotoxin producers and can also be responsible for opportunistic infections. In recent years, MALDI-TOF MS has emerged as a valuable, rapid and reliable asset for fungal identification in order to ensure food safety and quality. In this context, this study aimed at expanding the VITEK® MS database with food-relevant fungal species and evaluate its performance, with a specific emphasis on species differentiation within species complexes. To this end, a total of 380 yeast and mold strains belonging to 51 genera and 133 species were added into the spectral database including species from five species complexes corresponding to Colletotrichum acutatum, Colletotrichum gloeosporioides, Fusarium dimerum, Mucor circinelloides complexes and Aspergillus series nigri. Database performances were evaluated by cross-validation and external validation using 78 fungal isolates with 96.55% and 90.48% correct identification, respectively. This study also showed the capacity of MALDI-TOF MS to differentiate closely related species within species complexes and further demonstrated the potential of this technique for the routine identification of fungi in an industrial context. [ABSTRACT FROM AUTHOR]

[Objective] The purpose of the paper was to study the diversity and growth promoting potential of culturable endophytic fungi in Neuwiedia singapureana, and provide a reference for the exploration of endophytic fungi resources in Hainan of China. (Method) The endo- phytic fungi strains of N. singapureana rooted from the Dialuoshan Nature Reserve in Hainan province were identified by culture method, combined with ITS sequencing, and the phosphorus dissolving and growth promotion ability of some fungi was tested. The endophytic fungi was co-cultured with the protocorms of D. officinale and A. rigida, to test their effects on the growth of the two orchids. (Result) By free- hand sections and microscopic observation, the fungal hypha in the cortex of root of the N. singapureana could be clearly observed. 24 OTUS were obtained, belonging to nine families and 14 genera, among which Trichoderma in Moniliaceae family had the highest isolation rate, with five genera (eg. Cylindrocarpon, Gliocephalotrichum) strains in Nectriaceae followed. Among them, five strains showed different degrees of phosphorus-decompressing ability, contaning Apiotrichum sp. (Neu242), Cylindrocarpon spp. (Neu83 and Neul54), Gliocladiopsis sp. (Neu245) and Mucor sp. (Neul23). Morover, Mucor sp. Neu123 and Apiotrichum sp. Neu242, showed significantly promoting effects on the growth of D. officinale and A. rigida seedlings. [Conclusion] There are abundant culturable fungi in the roots of N. singapureana. The endophytic fungi with potential phosphorus-soluble ability are screened from N. singapureana roots, which can provide growth-promoting strain resources for the artificial breeding of orchids, and also lay a foundation for the research on the mechanism of orchid mycorrhiza symbiotic phosphorus nutrition. [ABSTRACT FROM AUTHOR]

Mucor indicus Lendn. 1930 has been widely used in food fermentation; however, its mitochondrial genome characteristics are not well understood. In this study, the complete mitochondrial genome of M. indicus was obtained, which was 61,400 bp in length with a GC content of 33%. The M. indicus mitochondrial genome was found to contain 14 core protein-coding genes, four free-standing ORFs, 18 intronic ORFs, 26 tRNAs, and two rRNA genes. Phylogenetic trees were generated for 25 early-differentiated fungi using the Bayesian inference (BI) method, which demonstrated that M. indicus is closely related to Mucor piriformis. This study provides useful information for the classification and evolution of Mucor species or other early-differentiated fungi. [ABSTRACT FROM AUTHOR]

This study aimed to enhance sludge dewatering through sequential bioleaching, employing the filamentous fungus Mucor sp. ZG-3 and the iron-oxidizing bacterium Acidithiobacillus ferrooxidans LX5. The mechanism by which Mucor sp. ZG-3 alleviates sludge dissolved organic matter (DOM) inhibition of A. ferrooxidans LX5 was investigated, and the optimal addition of energy source for enhanced sludge dewaterability during sequential bioleaching was determined. Sludge dissolved organic carbon (DOC) decreased to 272 mg/L with a 65.2% reduction by Mucor sp. ZG-3 in 3 days, and the degraded fraction of sludge DOM was mainly low-molecular-weight DOM (L-DOM) which inhibited the oxidization of Fe2+ by A. ferrooxidans LX5. By degrading significant inhibitory low-molecular-weight organic acids, Mucor sp. ZG-3 alleviated DOM inhibition of A. ferrooxidans LX5. In the sequential bioleaching process, the optimal concentration of FeSO4·7H2O for A. ferrooxidans LX5 was 4 g/L, resulting in the minimum specific resistance to filtration (SRF) of 2.60×1011 m/kg, 40.0% lower than that in the conventional bioleaching process with 10 g/L energy source. Moreover, the sequential bioleaching process increased the sludge zeta potential (from -31.8 to -9.47 mV) and median particle size (d50) of the sludge particle (from 17.90 to 27.44 μm), contributing to enhanced sludge dewaterability. Inoculation of Mucor sp. ZG-3 during the bioleaching process reduced the demand for energy sources by A. ferrooxidans LX5 while improving sludge dewaterability performance. [ABSTRACT FROM AUTHOR]

The biological control of gastrointestinal (GI) parasites using predatory fungi has been recently proposed as an accurate and sustainable approach in birds. The current study aimed to assess for the first time the efficacy of using the native ovicidal fungus Mucor circinelloides (FMV-FR1) in reducing coccidia parasitism in peacocks. For this purpose, an in vivo trial was designed in the resident peacock collection (n = 58 birds) of the São Jorge Castle, at Lisbon, Portugal. These animals presented an initial severe infection by coccidia of the genus Eimeria (20106 ± 8034 oocysts per gram of feces, OPG), and thus received commercial feed enriched with a M. circinelloides suspension (1.01 × 108 spores/kg feed), thrice-weekly. Fresh feces were collected every 15 days to calculate the coccidia shedding, using the Mini-FLOTAC technique. The same bird flock served simultaneously as control (t0 days) and test groups (t15–t90 days). The average Eimeria sp. shedding in peacocks decreased up to 92% following fungal administrations, with significant reduction efficacies of 78% (p = 0.004) and 92% (p = 0.012) after 45 and 60 days, respectively. Results from this study suggest that the administration of M. circinelloides spores to birds is an accurate solution to reduce their coccidia parasitism. [ABSTRACT FROM AUTHOR]

PurposeCoinfections or consecutive infections of Mucor and Aspergillus are exceedingly uncommon in children, we report the case to offer the valuable experience for colleagues facing similar situations.Case reportThis report documents the first recorded case of successful treatment for pulmonary mixed infection in a diabetic girl. Initially, the patient underwent treatment based on voriconazole, but the infection continued to deteriorate. Subsequently, bronchoalveolar lavage fluid culture and metagenomic next-generation sequencing (mNGS) were conducted, leading to a clear diagnosis of simultaneous infection by Aspergillus fumigatus and Rhizopus microsporus. Susceptibility testing revealed fungal resistance to voriconazole. Therefore, a combined treatment regimen of AmB liposomes and isavuconazole effectively eradicated the fungal infection.ConclusionThis case underscores the importance of early and precise identification of fungal pathogens, determination of effective antifungal medications, and timely implementation of well-planned therapeutic strategies. Furthermore, we comprehensively reviewed 10 cases of pulmonary mixed infections involving Mucor and Aspergillus, summarizing their characteristics and identifying commonalities.

Abstract Cardiovascular diseases, resulting from the deposition of clots in blood vessels, are the leading cause of death worldwide. Fibrinolytic enzymatic activity can catalyze blood clot degradation. Findings show that 36 fungal isolates recovered from Caatinga soils have the potential to produce fibrinolytic protease under submerged conditions. About 58 % of the isolates displayed fibrinolytic activity above 100 U/mL, with Mucor subtilissimus UCP 1262 being the most active. The protease was biochemically and biophysically characterized, showing that the enzyme had a high affinity for SAApNA substrate and was significantly inhibited by fluoride methyl phenyl sulfonyl-C7H7FO2S, suggesting that it is a chymotrypsin-like serine protease. The highest enzyme activity was detected at pH 5.0 and 28 °C. This fibrinolytic protease’s far-UV circular dichroism (CD) showed that its secondary structure was primarily α-helical. The purified fibrinolytic enzyme may represent a novel therapeutic agent for treating thrombosis. At temperatures above 65 °C, the enzyme lost all its secondary structure. Its melting temperature was 58.1 °C, the denaturation enthalpy 85.1 kcal/mol, and the denaturation entropy 0.26 kcal/K∙mol.

ABSTRACT:This is a case report of a 46-year-old female with undiagnosed diabetes, COVID-19, and mucormycosis. Mucormycosis is a rare, rapidly progressive disease process characterized by an insidious onset of vague symptoms and is associated with a high mortality rate. The patient initially presented at two outside ophthalmology clinics due to right eye pain and was prescribed steroids. Upon presentation to our institution’s Emergency Department, the patient’s pain had significantly increased along with new symptoms of ptosis and failure to adduct the right eye. Laboratory results demonstrated leukocytosis, hyperglycemia, and a positive SARS-CoV-2 test. Magnetic resonance imaging confirmed a diagnosis of mucormycosis and the patient underwent surgery and began intravenous antifungal therapy. This discussion addresses the presenting features of mucormycosis in the emergency department while highlighting the need for immediate investigation due to the fungi’s rapidly progressive nature.Topics: Mucormycosis, mucor, diabetes, COVID-19, ROCM.

Abstract Mucorales are basal fungi that opportunistically cause a potentially fatal infection known as mucormycosis (black fungus disease), which poses a significant threat to human health due to its high mortality rate and its recent association with SARS-CoV-2 infections. On the other hand, histone methylation is a regulatory mechanism with pleiotropic effects, including the virulence of several pathogenic fungi. However, the role of epigenetic changes at the histone level never has been studied in Mucorales. Here, we dissected the functional role of Set1, a histone methyltransferase that catalyzes the methylation of H3K4, which is associated with the activation of gene transcription and virulence. A comparative analysis of the Mucor lusitanicus genome (previously known as Mucor circinelloides f. lusitanicus) identified only one homolog of Set1 from Candida albicans and Saccharomyces cerevisiae that contains the typical SET domain. Knockout strains in the gene set1 lacked H3K4 monomethylation, dimethylation, and trimethylation enzymatic activities. These strains also showed a significant reduction in vegetative growth and sporulation. Additionally, set1 null strains were more sensitive to SDS, EMS, and UV light, indicating severe impairment in the repair process of the cell wall and DNA lesions and a correlation between Set1 and these processes. During pathogen-host interactions, strains lacking the set1 gene exhibited shortened polar growth within the phagosome and attenuated virulence both in vitro and in vivo. Our findings suggest that the histone methyltransferase Set1 coordinates several cell processes related to the pathogenesis of M. lusitanicus and may be an important target for future therapeutic strategies against mucormycosis.

To select high-efficiency strains suitable for semi-dry black douchi fermentation, this study compared and analyzed the koji-making effects of six Aspergillus oryzae strains and one Lichtheimia corymbifera strain with large differences in enzyme-producing capacity. The results showed that A. oryzae HN3.042, DM1 and DM2 had a strong ability to metabolize amylase, and the fermented douchi had a lower L* value. A. oryzae 24M-1, 30M-1, and PNM003 had a strong ability to produce protease, aminopeptidase, and carboxypeptidase, resulting in greater utilization of protein substrates and higher contents of total acid and amino nitrogen in the fermented douchi. In terms of volatile flavor substances, the douchi fermented with stains HN3.042, DM1, and DM2 had a relatively higher content of 1-octen-3-ol, isovaleric acid, and 4-methylpentanoic acid. The douchi fermented with strains 24M-1, 30M-1, and PNM003 had a relatively higher content of trans-2-nonenal, 3-octanone, and isophorone, resulting in richer and better flavor quality. L. corymbifera QM3 had lower enzymatic activity when compared with A. oryzae, resulting in poorer physicochemical indicators, lower contents of free amino acids and volatile flavor substances and poorer quality in douchi. The study suggests that the quality of douchi is related to the enzyme-producing capacity of the koji mold. The predominance of amylase in the koji enzyme system is conducive to the formation of color and acidic flavor substances in douchi, while with the predominance of proteolytic enzymes is conducive to the formation of amino nitrogen and good flavor quality in douchi.

Simple Summary: The lipid yield of Mucor circinelloides WJ11 has been much studied for industrial production improvement. In this study, the carRP gene responsible for the production of carotenoids was knocked out, which resulted in the interruption of the carotenoid production pathway and a simultaneous impact on lipid production. Further, an integrative transcriptome and genome-scale metabolic model-driven analysis was conducted, which provides insights into the coordinated relationship between carotenoid and fatty acid biosynthesis in M. circinelloides. The findings can be used to design efficient M. circinelloides cell factories. Mucor circinelloides WJ11 is a lipid-producing strain with industrial potential. A holistic approach using gene manipulation and bioprocessing development has improved lipid production and the strain's economic viability. However, the systematic regulation of lipid accumulation and carotenoid biosynthesis in M. circinelloides remains unknown. To dissect the metabolic mechanism underlying lipid and carotenoid biosynthesis, transcriptome analysis and reporter metabolites identification were implemented between the wild-type (WJ11) and ΔcarRP WJ11 strains of M. circinelloides. As a result, transcriptome analysis revealed 10,287 expressed genes, with 657 differentially expressed genes (DEGs) primarily involved in amino acid, carbohydrate, and energy metabolism. Integration with a genome-scale metabolic model (GSMM) identified reporter metabolites in the ΔcarRP WJ11 strain, highlighting metabolic pathways crucial for amino acid, energy, and nitrogen metabolism. Notably, the downregulation of genes associated with carotenoid biosynthesis and acetyl-CoA generation suggests a coordinated relationship between the carotenoid and fatty acid biosynthesis pathways. Despite disruptions in the carotenoid pathway, lipid production remains stagnant due to reduced acetyl-CoA availability, emphasizing the intricate metabolic interplay. These findings provide insights into the coordinated relationship between carotenoid and fatty acid biosynthesis in M. circinelloides that are valuable in applied research to design optimized strains for producing desired bioproducts through emerging technology. [ABSTRACT FROM AUTHOR]

The food enzyme triacylglycerol lipase (triacylglycerol acylhydrolase, EC 3.1.1.3) is produced with the non‐genetically modified Mucor circinelloides strain AE‐LMH by Amano Enzyme Inc. A safety evaluation of this food enzyme was made previously, in which EFSA concluded that this food enzyme did not give rise to safety concerns when used in three food manufacturing processes. Subsequently, the applicant requested to extend its use to include two additional processes. In this assessment, EFSA updated the safety evaluation of this food enzyme when used in a total of five food manufacturing processes. The dietary exposure to the food enzyme‐total organic solids (TOS) was estimated to be up to 0.845 mg TOS/kg body weight (bw) per day in European populations. When combined with the no observed adverse effect level previously reported (784 mg TOS/kg bw per day, the highest dose tested), the Panel derived a margin of exposure of at least 928. Based on the data provided for the previous evaluation and the revised margin of exposure, the Panel concluded that this food enzyme does not give rise to safety concerns under the revised intended conditions of use. [ABSTRACT FROM AUTHOR]

The incidence of colon perforation in the posttransplant period is 1.3% based on various single‑center studies. We report the case of a 32‑year‑old male, a known case of chronic kidney disease and end‑stage renal disease who received a live‑related ABO‑compatible transplant. The patient was started on tacrolimus, mycophenolate mofetil, and steroids; no induction was given. The patient had a delayed graft function, and his creatinine was persistently high. Hence, a biopsy was done on postoperative day 4, which revealed an acute tubular injury with features of calcineurin inhibitor toxicity. His tacrolimus dose was reduced and his output improved until day 13, after which his renal function worsened. The repeat tacrolimus level was low. Hence, the patient was started on pulse steroids and discharged after the patient improved symptomatically (discharge creatinine: 2.1). The patient was readmitted 3 days after discharge with severe abdominal pain. The patient’s blood pressure was 90/30 mmHg; he was drowsy and tachypneic. His abdomen was distended. Computed tomography of the abdomen revealed pneumoperitoneum, and the patient was subjected to an explorative laparotomy. There was colonic perforation. The peritoneum and colon revealed multiple punched‑out lesions and a right hemicolectomy was done. A biopsy revealed suppurative inflammation involving all three layers with multiple giant cells, and tissue staining revealed ribbon‑like aseptate hyphae with 90° angulation suggestive of mucormycosis. The patient expired in the immediate postoperative period. The final diagnosis of mucormycosis‑associated colon perforation was made. Only one such case has been reported previously. [ABSTRACT FROM AUTHOR]

Introduction: There is an upsurge of Mucor Mycosis infection following Covid -19 pandemic. Disordered immune system due to covid19 infection coupled with indiscriminate use of steroids is believed to be responsible for this upsurge. Objectives: This study is aimed at analysing the preliminary epidemiological data of Mucormycosis patients admitted in a single tertiary care centre, stage them at presentation and to devise a treatment protocol according to their stage .To study the various surgical interventions, postoperative follow-up and treatment outcomes in terms of recovery rateand recurrence. Patients and Methods: This is a prospective longitudinal study, one of the largest of its kind involving around 1841 patients diagnosed as Mucormycosis and admitted in a tertiary care hospital in India. A detailed case history, Diagnostic nasal endoscopy, CECT scan and MRI Scan were done. A novel staging was devised and patients were managed medically and surgically as per the stage. Debrided tissue was sent for microbiological and histopathological confirmation. Patients were followed-up and their recovery rates were analysed. Results: Among 1841 patients of mucor mycosis studied, 1288 were Rhino orbital and 78 were Rhino cerebral type. 1229 patients under went surgical debridement according to the stage of disease, and rest were managed conservatively. Recovery rates fell from 90% to 26% from stage I to stage IV due to in volvement of CNS and Orbits .The mortality was as low as 17%. Re -do surgeries were done in only 12% of cases. Conclusion: Staging of mucor at presentation helps in planning, assessing response of treatment and prognosis. [ABSTRACT FROM AUTHOR]

Introduction: Mucormycosis, an infection, with a high death rate, requires understanding its symptoms, diagnosis methods and treatment options due, to its growing occurrence. The research employs a molecular method to evaluate the diagnosis of the mucormycosis. Materials and Methods: In this study, we obtained 30 samples from patients undergoing diagnosis and conducted DNA extraction. Additionally, DNA extraction was carried out on 30 tissue samples suspected of infection in paraffin blocks. Subsequently, PCR and Real-time PCR were performed using targeted primers, for mucormycosis followed by analysis of the results. Results: In the research findings among 30 liquid samples 8 tested positive, for mucor using the PCR method. 10 using the Real-time PCR method. Similarly, out of 30 tissue samples, 9 cases showed mucor presence with the PCR method and 11 cases, with the Realtime PCR method. Conclusion: In this study, real-time PCR and PCR techniques showed promising and faster results in detecting Mucor than the culture approach. The molecular methods provided results that could be of great use for scenarios. [ABSTRACT FROM AUTHOR]

Postharvest spoilage of strawberry grown under protection, caused by Mucor spp. and Rhizopus spp., has recently become more common in the UK, but there is insufficient knowledge to develop and implement integrated management against Mucor and Rhizopus. Field sampling was conducted to obtain field data for developing models to predict the infection of Mucor and Rhizopus on strawberry fruit. Fruits were exposed to naturally occurring inoculum for a period of 24 hours before surface-sterilisation and incubation to estimate the level of infection by Mucor and Rhizopus. The observed incidence data, together with climatic conditions and inoculum trap counts, were used analysed firstly within the framework of (1) generalised linear model (GLM), and (2) classification tree. Field sampling confirmed previous research that ripening/ripe strawberry fruits are more susceptible to infection by Mucor and Rhizopus. Climatic variability, particularly in vapour pressure deficit, appears to be more important in influencing the rotting incidence of both Mucor and Rhizopus. However, the predictability of both Mucor and Rhizopus, whether as a continuous variable (incidence) in the GLM analysis or as a categorical risk in classification tree analysis, is too low to be of practical value based on those predictors used in the present study. Thus, current management may have to be based on scheduled preharvest application of alternative products to reduce infection and local pathogen inoculum as well as adopting management practice to minimise pathogen inoculum in the planting. Future research is needed to develop methods for rapid yet accurate in situ quantification of pathogen inoculum to improve disease risk predictions. [ABSTRACT FROM AUTHOR]

Background: Mucormycosis is an invasive fungal infection that occurs in immunodeficiency patients and belongs to infections caused by mucoral fungi, such as Rhizopus and Rhizomucor. Objectives: This study investigated the identification and detection of the mucor fungus in tissue samples and other samples by the real-time polymerase chain reaction (PCR) method. Methods: This was a cross-sectional-descriptive study. Atotal of 80 tissue samples were collected from referring patients to diagnose fungi with the opinion of a specialist doctor. After extracting deoxyribonucleic acid (DNA) from the samples, PCR and real-time PCR tests were performed using specific primers for mucor and universal-pan and compared to culture. The results were confirmed by sequencing. Results: In this study, 80 samples were examined. In the PCR method, 74 and 75 cases of fungi were confirmed from the DNA obtained from the colonies and tissues, respectively. By using a specific primer for mucor, 12 patients were reported as positive for mucor. Additionally, 76 and 77 cases of fungi were confirmed in the real-time PCR method from the DNA obtained from the colonies and tissues, respectively, and positive cases were reported. By using specific primers and the real-time PCR test for mucor, 16 cases of mucor were reported from colonies, and 15 cases of mucor were reported positive from tissues. Conclusions: This study showed that real-time PCR and PCR are high-speed and more accurate methods than the culture test in identifying its species and have acceptable results in clinical cases. [ABSTRACT FROM AUTHOR]

In this present study, potential oleaginous Mucorales fungi that have been isolated from fruits from local markets in Sleman, Indonesia, were screened for lipid production. A total of six fungal cultures were isolated and screened using a semisynthetic medium with glucose as a carbon source and a limited nitrogen supply. The highest lipid content was observed in isolate JR 1.1, up to 43.46% and 3.28 g/L lipid yield. Therefore, it was selected for molecular identification and fatty acid analysis. The result showed that JR 1.1 was identified as Mucor irregularis. The fatty acid profile of JR 1.1 showed 16.89% palmitoleic acid, 4.85% oleic acid, 45.22% linolenic acid, 30.79% gamma-linolenic acid, and 2.25% other fatty acids. It can be concluded that M. irregularis JR 1.1 is a potential strain to be used as a lipid producer for biodiesel feedstock. Further studies are recommended to optimize lipid productivity and improve fatty acid composition. [ABSTRACT FROM AUTHOR]

Mucormycosis is an invasive fungal infection that can cause acute clinical decompensation and death. The literature demonstrates case fatality rates around 50% with differential clinical courses contingent upon anatomical incursion. Rhino-orbital cerebral mucormycosis represents a rapidly hostile variant with poorer outcomes, warranting prompt recognition, workup, and intervention. It is seldom included in differential diagnoses in those with head and neck pathology within the inpatient setting as diagnostic parsimony and low prevalence lead this entity to be often overlooked. Given the acuity and risk factors involved, considering mucormycosis may be prudent during the assessment of hyperglycemic or immunodeficient patients exhibiting maxillofacial disease. When acquiring histories of presenting illness and performing physical examinations, assessment includes mindfulness of diabetes mellitus, craniofacial lesions, and alertness to clinical deterioration. Given the rising incidence of complicated diabetes mellitus in conjunction with a paucity of mucormycosis reports noting the orbit as the diagnostic harbinger, we report the case of a 59-year-old woman admitted to the critical care setting for diabetic ketoacidosis and altered mental status. Physical examination revealed a swollen orbit, later diagnosed as mucormycosis with associated sino-orbit involvement and cranial nerve deficits warranting urgent and extensive facial debridement. [ABSTRACT FROM AUTHOR]

Purpose: Acute invasive fungal rhinosinusitis (AIFRS) is a rare, fulminant, angio-invasive infection with high mortality rate. Treatment of AIFRS includes aggressive surgical debridement combined with antifungal agents and treatment of the underlying disease. The aim of this study is to report our experience with this often fatal disease and estimate the long-term survival of AIFRS patients with more conservative surgery. Methods: A retrospective study was performed on immunocompromised adults with AIFRS from January 2011 to December 2020. The diagnosis was histologically confirmed by tissue fungus invasion. We analyze epidemiological and microbiological findings, the underlying disease and discuss our patients' treatment plan and long-term survival. Results: Fourteen patients were included in the study. Mean age was 53.8 ± 18.9 years. The underlying disease was hematologic malignancy in nine patients, diabetes mellitus in three, aplastic anemia in one, and renal/liver failure in one. Leukopenia was not significantly correlated with outcome or survival. Histological and culture findings revealed that Mucor/Rhizopus were the causative organisms in nine cases. All patients received systemic antifungal therapy. Surgery was performed in nine patients (endoscopic for all patients, combined in three with an external approach). Overall survival was 35.7% as five patients survived, two who underwent surgery, and three who were treated non-surgically. Nine patients died, two from AIFRS after central nervous system involvement and seven from their primary disease, free of fungi. Older individuals and patients with hematologic malignancies had a worse outcome. Conclusion: Early surgical debridement, antifungal agents, and treatment of the underlying disease remain the cornerstones of AIFRS management. Prognosis is overall defined by the underlying disease and in some selected cases, medical treatment alone could be a reasonable option. [ABSTRACT FROM AUTHOR]

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Pork backfat (PB) contains excessive saturated fatty acids (SFAs), but lacks polyunsaturated fatty acids (PUFAs). Excessive SFAs can be used as a substrate for the growth of certain microorganisms that convert them into PUFAs and monounsaturated fatty acids (MUFAs), and the added value of PB can be enhanced. In this study, Mucor circinelloides CBS 277.49 and Lactiplantacillus plantarum CGMCC 24189 were co-cultured for conversion of PB into fermented pork backfat (FPB) with high level of PUFAs. Our results showed that the content of γ-linolenic acid (GLA) and linoleic acid (LA) in the surface of FPB reached 9.04 ± 0.14 mg/g and 107.31 ± 5.16 mg/g for 7-day fermentation, respectively. To convert the internal SFAs of PB, ultrasound combined with papain was used to promote the penetrative growth of M. circinelloides into the internal PB, and the GLA level in the third layer of fat reached 2.58 ± 0.31 mg/g FPB. The internal growth of M. circinelloides in PB was promoted by adjusting the oxygen rate and ventilation rate through the wind velocity sensor. When the oxygen rate is 2 m/s and the ventilation rate is 18 m3/h, the GLA level in the third layer of fat reached 4.13 ± 1.01 mg/g FPB. To further improve the level of PUFAs in PB, FPB was produced by M. circinelloides at 18 °C. The GLA content on the surface of FPB reached 15.73 ± 1.13 mg/g FPB, and the GLA yield in the second and third layers of fat reached 8.68 ± 1.77 mg/g FPB and 6.13 ± 1.28 mg/g FPB, the LA yield in the second and third layers of fat reached 105.45 ± 5.01 mg/g FPB and 98.46 ± 4.14 mg/g FPB, respectively. These results suggested that excessive SFAs in PB can be converted into PUFAs and provided a new technique for improving PUFAs in FPB. Key points: • This article achieved the conversion of PUFAs in pork backfat by Mucor circinelloides CBS 277.49 and Lactiplantacillus plantarum CGMCC 24189. • This article solved the internal growth of M. circinelloides CBS277.49 in pork backfat by ultrasound combined with papain. • This article proposed an innovative of promoting the internal growth of M. circinelloides and increasing the PUFAs production by oxygen ventilation in pork backfat. [ABSTRACT FROM AUTHOR]

Summary: Sufu, a traditional Chinese fermented soybean food, had its flavour and quality influenced by the specific strains and fermentation environment. To investigate how microbial community succession affects the volatile aroma substances of Mucor racemosus sufu during fermentation, the microbial community structure using high‐throughput sequencing (HTS) technology was analysed. Additionally, volatile flavour compounds using solid‐phase microextraction gas chromatography mass spectrometry (SPME‐GC–MS) were detected. Throughout the pre‐fermentation, salting, and post‐fermentation stages, the changes in the microbial communities over time and space due to environmental variations were observed. The colony compositions at the phylum and genus levels were also analysed. The results revealed that Proteobacteria and Actinobacteria were the dominant bacterial phyla in the final fermented product. Furthermore, several microorganisms associated with flavour substances were identified, such as Lactobacillus, Pseudomonas, Wescheria, Hyphomyces, Candida, and Pichia. These microorganisms primarily influenced the synthesis of alcohols and acids, contributing to the overall flavour profile of the sufu. In the analysis of the final product, it identified fifty‐four volatile flavour compounds, including alcohols, esters, phenolic acids, aldehydes, ketones, ether, alkenes, and other compounds. These findings have important implications for isolating specific strains, enhancing flavour, and providing a solid foundation for optimising and ensuring the quality of sufu. [ABSTRACT FROM AUTHOR]

The second wave of COVID pandemic was associated with an outbreak of Mucormycosis. The mortality rate of Mucormycosis reaches 50–80% in cases with orbital and intracranial extension (Fadda in Acta Otorhinolaryngol Ital 41:43–50, 2021). In this outbreak we found that few of these patients had bacterial invasive sinusitis mimicking fungal sinusitis. Amphotericin the only effective drug against Mucormycosis is highly toxic and expensive and not indicated in bacterial sinusitis. Our aim was to determine the exact etiologic agent, predisposing factors and outcome of treatment of COVID associated invasive sinusitis presenting with orbital complications. It is a retrospective observational study done in 33 patients with orbital complications in COVID associated invasive sinusitis. Demographic details of the patients and clinical presentation were documented. Rhinological examination was done and a nasal swab was taken for KOH mount along with Gram's stain and Culture and Sensitivity. All Patients underwent radiological evaluation by contrast enhanced computed tomography (CECT) or MRI. Liposomal Amphotericin B was started. Surgical debridement done. Amphotericin-B was stopped in cases reported negative for fungal elements and antibiotics administered for two weeks. Outcome of treatment was documented. A total of 33 patients were included in the study. 48.5% patients were found to have bacterial infection and 27.3% patient's fungal infections and 24.2% mixed infections.Eschar formation, necrotic tissue, erosion of the lamina papyracea was seen in both Klebsiella (33.3%) and Staphylococcal infections (16.6%) similar to Mucor and mixed infections. Persistent opthalmoplegia and deterioration of vision was associated with Mucor and mixed infections. However improvement in proptosis, ptosis, ophthalmoplegia, and vision was observed in cases associated with bacterial invasive sinusitis. Invasive bacterial sinusitis was under diagnosed during second wave of COVID. Identification of invasive bacterial sinusitis can help in de-escalation of treatment. [ABSTRACT FROM AUTHOR]

Mucor circinelloides lipase Lip10 is a dual-functional enzyme with lipolytic activity and phospholipid:diacylglycerol acyltransferase (PDAT) activity in aqueous phase. However, the catalytic properties of Lip10 and its structural characteristics remain unknown. The present study systematically investigated its PDAT activity and lipolytic activity using six phospholipid substrates, 18:0 triacylglycerol and 16:0 1,2-diacylglycerol, predict the 3D structure of Lip10 using AlphaFold2, and evaluated residues' flexibility through molecular dynamics analysis. Lip10 exhibited a preference for phosphorylethanolamine (PE) with a long-chain fatty acyl group and showed the lipolytic activity to 18:0 triacylglycerol and 16:0 1.2-diacylglycerol. 20 mM Mg2+ and Fe2+ can significantly increase the PDAT activity of Lip10 by 50–80%. Molecular docking analysis suggest that the lower binding energy for 18:0 PE with Lip10 contributes to the higher structural stability of the complex of 18:0 PE and Lip10. Mutations of Phe565Asp and Glu318Met increase PDAT activity of Lip10 by 3.6-fold and 2.7-fold, while the TAG content produced by mutants Lip10Phe103Pro, Lip10Ile487Lys and Lip10Phe570Asp decrease by 33%− 43%. The present study demonstrated structural properties of the dual-functional lipase Lip10 and provide a theoretical basis to study its roles in the lipid metabolism of M. circinelloides in the future. [Display omitted] • Lip10 is a dual-functional enzyme with lipolytic activity and PDAT activity in aqueous phase. • Lip10 exhibited stronger PDAT activity when 18:0 PE was used as the substrate. • Lip10 showed the lipolytic activity to 18:0 triacylglycerol and 16:0 1.2-diacylglycerol. • Mutations of Phe565Asp and Glu318Met increase PDAT activity of Lip10 by 3.6-fold and 2.7-fold. • TAG produced by mutants Lip10Phe103Pro, Lip10Ile487Lys and Lip10Phe570Asp decrease by 33%− 43%. [ABSTRACT FROM AUTHOR]

Minor ginsenosides, known for their superior biological activities in comparison to major ginsenosides, are relatively scarce in nature. Therefore, this study explored the utility of Mucor abundans enzyme in transformating major ginsenosides obtained from the root and flower of Panax notoginseng into minor ginsenosides. Comprehensive analysis and verification of the conversion products (minor ginsenosides) were conducted employing an array of techniques, including TLC, HPLC, and MS. Additionally, the study proposed conversion pathways for the major ginsenosides by dynamically monitoring the changes of substrates and products during the conversion process. The study found that the M. abundans enzyme can successfully converted ginsenosides Rb 1 , Rb 2 , Rb 3 , Rc, Re, Rg 1 , and notoginsenoside R 1 from P. notoginseng into 22 minor ginsenosides via processes such as deglycosylation, epimerization and dehydration, with conversion rates varying from 37.0% to 98.9%. The enzyme, purified and presenting a molecular weight of approximately 69 kDa, primarily catalyzed the hydrolysis of glycoside bonds at positions C-3 and C-20 of PPD-type ginsenosides, and C-20 position of PPT-type ginsenosides, thus facilitating the conversion of major to minor ginsenosides. This exploration potentates the enhanced functionality and proportionately increased economic value of P. notoginseng. [Display omitted] • A Mucor abundant strain was screened, which had remarkable saponin conversion ability. • This enzyme converts the saponins in panax notoginseng into 22 minor ginsenosides. • The transformation pathways of major saponins were speculated and verified. • Control different time, temperature and pH can obtain targeted ginsenosides. • Laying a solid foundation for the large-scale production of minor ginsenosides. [ABSTRACT FROM AUTHOR]

Fresh Codonopsis pilosula is highly susceptible to fungus contamination during post-harvest storage, which not only compromises the quality of C. pilosula but also contributes mycotoxin contamination, posing a significant threat to human health. Studies have indicated that ozone treatment can inhibit post-harvest diseases in fruits and vegetables. The impact of ozone treatment on the disease incidence, disease severity index, and weight loss rate of the fresh C. pilosula infected with Actinomucor elegans was investigated through the spray inoculation of A. elegans on C. pilosula tissues. Changes in the main active ingredients of C. pilosula after ozone treatment were analyzed, and the effects of ozone treatment on the integrity of cell membranes in C. pilosula tissue and reactive oxygen species (ROS) metabolism were studied. The results showed that ozone treatment had a significant inhibitory effect on the A. elegans-induced mucor rot in C. pilosula, significantly reducing the incidence of the disease. Compared with the control group, the ozone-treated group maintained the effective components of C. pilosula well. Furthermore, ozone treatment reduced the cell membrane permeability and Malondialdehyde (MDA) content in C. pilosula, significantly increased the activity of antioxidant enzymes in the ROS metabolism pathway, prevented oxidative stress caused by the accumulation of ROS in C. pilosula tissues, and maintained the integrity of cell membranes. [ABSTRACT FROM AUTHOR]

In this study, the stool sample of a cockatiel (Nymphicus hollandicus Kerr, 1972), brought with complaints of loss of appetite, weight loss and bad smell in the stool, was examined mycologically. Serial dilutions of the stool sample were made under aseptic conditions and inoculated into Dichloran Rose-Bengal Chloramphenicol Agar (DRBC) and blood agar media. After incubation, the samples were separated as pure colonies and morphological, microscopic and molecular identifications were made from these pure colonies. Phenol-chloroform isoamylalcohol DNA isolation method was used for molecular identification. PCR amplification from fungal DNAs was carried out at Aydın Adnan Menderes University Biology Department Microbiology Laboratory and by commercial companies as service procurement. Sequencing services were provided by Innopenta Biotechnology and Macrogen Europe. Primers ITS1 (50-TCCGTAGGTGAACCTGCGG-30) / ITS4 (50-TCCTCCGCTTATTGATATGC-30) were used. The nBLAST program was used to identify fungi and species were matched according to their genetic similarity rates. Sequence results were recorded in the GenBank system and added to the culture collection. After molecular studies, Fusarium fujikuroi HBF578 and Mucor racemosus HBB579 strains were identified. When the literature studies were examined, it was seen that the Fusarium fujikuroi HBF578 strain had not been isolated from the Cockatiel before and was reported for the first time in this study. [ABSTRACT FROM AUTHOR]