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2.
Antimicrob Agents Chemother ; 68(5): e0154523, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38557112

RESUMEN

Ibrexafungerp (formerly SCY-078) is the first member of the triterpenoid class that prevents the synthesis of the fungal cell wall polymer ß-(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.


Asunto(s)
Anfotericina B , Antifúngicos , Glicósidos , Mucormicosis , Neutropenia , Triterpenos , Animales , Anfotericina B/uso terapéutico , Anfotericina B/farmacología , Mucormicosis/tratamiento farmacológico , Ratones , Antifúngicos/uso terapéutico , Antifúngicos/farmacología , Triterpenos/farmacología , Triterpenos/uso terapéutico , Neutropenia/tratamiento farmacológico , Neutropenia/complicaciones , Modelos Animales de Enfermedad , Quimioterapia Combinada , Femenino , Rhizopus/efectos de los fármacos , Enfermedades Pulmonares Fúngicas/tratamiento farmacológico , Enfermedades Pulmonares Fúngicas/microbiología , Mucor/efectos de los fármacos , Triazoles/uso terapéutico , Triazoles/farmacología
3.
Microbiol Spectr ; 12(5): e0407823, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38534121

RESUMEN

Parasiticide fungi are considered an accurate, sustainable, and safe solution for the biocontrol of animal gastrointestinal (GI) parasites. This research provides an initial characterization of the virulence of the native parasiticide fungus Mucor circinelloides (FMV-FR1) and an assessment of its impact on birds' gut microbes. The genome of this fungus was sequenced to identify the genes coding for virulence factors. Also, this fungus was checked for the phenotypic expression of proteinase, lecithinase, DNase, gelatinase, hemolysin, and biofilm production. Finally, an in vivo trial was developed based on feeding M. circinelloides spores to laying hens and peacocks three times a week. Bird feces were collected for 3 months, with total genomic DNA being extracted and subjected to long-read 16S and 25S-28S sequencing. Genes coding for an iron permease (FTR1), iron receptors (FOB1 and FOB2), ADP-ribosylation factors (ARFs) (ARF2 and ARF6), and a GTPase (CDC42) were identified in this M. circinelloides genome. Also, this fungus was positive only for lecithinase activity. The field trial revealed a fecal microbiome dominated by Firmicutes and Proteobacteria in laying hens, and Firmicutes and Bacteroidetes in peacocks, whereas the fecal mycobiome of both bird species was mainly composed of Ascomycetes and Basidiomycetes fungi. Bacterial and fungal alpha-diversities did not differ between sampling time points after M. circinelloides administrations (P = 0.62 and P = 0.15, respectively). Although findings from this research suggest the lack of virulence of this M. circinelloides parasiticide isolate, more complementary in vitro and in vivo research is needed to conclude about the safety of its administration to birds, aiming at controlling their GI parasites.IMPORTANCEA previous study revealed that the native Mucor circinelloides isolate (FMV-FR1) can develop parasiticide activity toward coccidia oocysts, one of the most pathogenic GI parasites in birds. However, ensuring its safety for birds is of utmost importance, namely by studying its virulence profile and potential effect on commensal gut microbes. This initial study revealed that although this M. circinelloides isolate had genes coding for four types of virulence factors-iron permease, iron receptors, ADP-ribosylation factors, and GTPase-and only expressed phenotypically the enzyme lecithinase, the administration of its spores to laying hens and peacocks did not interfere with the abundances and diversities of their gut commensal bacteria and fungi. Although overall results suggest the lack of virulence of this M. circinelloides isolate, more complementary research is needed to conclude about the safety of its administration to birds in the scope of parasite biocontrol programs.


Asunto(s)
Pollos , Microbioma Gastrointestinal , Mucor , Factores de Virulencia , Mucor/genética , Mucor/patogenicidad , Animales , Pollos/microbiología , Virulencia , Factores de Virulencia/genética , Factores de Virulencia/metabolismo , Heces/microbiología , Femenino
4.
Bioresour Technol ; 398: 130540, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38452954

RESUMEN

This study aimed to improve the lipid and biomass yields of Mucor circinelloides WJ11 by implementing four different fed-batch fermentation strategies, varied in time and glucose concentration (S1-S4). The S1 fermentation strategy yielded the highest biomass, lipid, and fatty acid content (22 ± 0.7 g/L, 53 ± 1.2 %, and 28 ± 1.6 %) after 120 and 144 h, respectively. The γ-linolenic acid titer of 0.75 ± 0.0 g/L was greatest in S3 after 48 h. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to analyze the transcription of key genes involved in lipid accumulation. The glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and ATP-citrate lyase genes showed increased expression levels. Fourier-transform infrared (FTIR) spectroscopy was used to analyze the biochemical profile during fermentation strategies. Optimal abiotic factors for production efficiency included pH 6.5, 25-26 °C, 15 % (v/v) inoculum, 500 rpm, 20 %-30 % dissolved oxygen, and 120 h fermentation. Glucose co-feeding offers valuable insights to develop effective fermentation strategies for lipid production.


Asunto(s)
Ácidos Grasos , Mucor , Fermentación , Biomasa , Mucor/metabolismo , Ácidos Grasos/metabolismo , Glucosa/metabolismo
5.
Food Res Int ; 181: 114118, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38448091

RESUMEN

Meat dry aging consists in storing unpackaged meat in a cold room, and at a specific and controlled relative humidity (RH), for a period of 1 to 5 weeks or more. This practice has become widespread in recent years due to its positive effect on the tenderness of the meat but also on other organoleptic characteristics and therefore its market value. The objective of this work was to study the bacterial and fungal microbiota of dry-aged beef at the commercial stage by both culture-dependent and -independent approaches. Fifty-eight samples of dry-aged meat from different producer types (meat processing plants, artisanal and supermarket butchers) were studied. The dry-aging conditions (temperature, RH) of the meats, as well as the surface pH and aw, were measured. The main microbial groups were enumerated by culture on various dedicated media. Concerning fungi, isolates of yeasts and molds (n = 257) were identified after dereplication by FTIR spectroscopy and/or sequencing of taxonomically relevant genes (26S rDNA, ITS, ß-tubulin, actin). Metagenetic analyzes targeting the V3-V4 regions of 16S rDNA and ITS2 were also performed. Overall, ripening practices were diversified with temperatures and RH between 0.5 and 2.8 °C (median = 2 °C) and 47 and 88 % (median = 70 %), respectively. The aerobic colony count varied between 1.97 and 10.91 log10 CFU/g (median = 8.32 log10 CFU/g) and was similar to that of Pseudomonas spp., indicating that this bacterial group was dominant. Yeast populations varied between <2 and 9.41 log10 CFU/g, while molds showed abundances between <2 and 7.7 log10 TFU/g, the highest values being found in meats matured with a high RH. Bacterial and mold counts were positively correlated with the dry-aging RH and, to a lesser extent, temperature. The main yeast species were Candida zeylanoides and Yarrowia alimentaria as well as Itersonilia pannonica (identified only in metagenetics). The dominant mold species were psychrophilic or psychrotrophic species, namely Mucor complex flavus and Helycostylum elegans/pulchrum that have already been shown to be associated with dry-aged beef meat. This study has identified the main microorganisms associated with dry-aged meat in France, which raises the question of their role in the organoleptic quality of these higher value products.


Asunto(s)
Microbiota , Mucor , Micobioma , Animales , Bovinos , Francia , ADN Ribosómico
6.
BMC Vet Res ; 20(1): 63, 2024 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-38388939

RESUMEN

BACKGROUND: The combined application of predatory fungi and antiparasitic drugs is a sustainable approach for the integrated control of animal gastrointestinal (GI) parasites. However, literature addressing the possible interference of antiparasitic drugs on the performance of these fungi is still scarce. This research aimed to assess the in vitro susceptibility of six native coccidicidal fungi isolates of the species Mucor circinelloides and one Mucor lusitanicus isolate to several antiparasitic drugs commonly used to treat GI parasites' infections in birds, namely anthelminthics such as Albendazole, Fenbendazole, Levamisole and Ivermectin, and anticoccidials such as Lasalocid, Amprolium and Toltrazuril (drug concentrations of 0.0078-4 µg/mL), using 96-well microplates filled with RPMI 1640 medium, and also on Sabouraud Agar (SA). RESULTS: This research revealed that the exposition of all Mucor isolates to the tested anthelminthic and anticoccidial drug concentrations did not inhibit their growth. Fungal growth was recorded in RPMI medium, after 48 h of drug exposure, as well as on SA medium after exposure to the maximum drug concentration. CONCLUSIONS: Preliminary findings from this research suggest the potential compatibility of these Mucor isolates with antiparasitic drugs for the integrated control of avian intestinal parasites. However, further in vitro and in vivo studies are needed to confirm this hypothesis.


Asunto(s)
Antiparasitarios , Mucor , Animales , Antiparasitarios/farmacología , Ivermectina/farmacología , Albendazol
7.
Environ Res ; 249: 118385, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38331140

RESUMEN

Silkworm pupae, by-product of sericulture industry, is massively discarded. The degradation rate of silkworm pupae protein is critical to further employment, which reduces the impact of waste on the environment. Herein, magnetic Janus mesoporous silica nanoparticles immobilized proteinase K mutant T206M and Mucor circinelloides aspartic protease were employed in the co-degradation. The thermostability of T206M improved by enhancing structural rigidity (t1/2 by 30 min and T50 by 5 °C), prompting the degradation efficiency. At 65 °C and pH 7, degradation rate reached the highest of 61.7%, which improved by 26% compared with single free protease degradation. Besides, the immobilized protease is easy to separate and reuse, which maintains 50% activity after 10 recycles. Therefore, immobilized protease co-degradation was first applied to the development and utilization of silkworm pupae resulting in the release of promising antioxidant properties and reduces the environmental impact by utilizing a natural and renewable resource.


Asunto(s)
Bombyx , Endopeptidasa K , Nanopartículas de Magnetita , Mucor , Pupa , Bombyx/metabolismo , Animales , Mucor/enzimología , Nanopartículas de Magnetita/química , Endopeptidasa K/metabolismo , Enzimas Inmovilizadas/metabolismo , Enzimas Inmovilizadas/química , Proteasas de Ácido Aspártico/metabolismo , Proteasas de Ácido Aspártico/química , Proteínas de Insectos/metabolismo , Proteínas de Insectos/química
8.
Appl Microbiol Biotechnol ; 108(1): 223, 2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-38376614

RESUMEN

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.


Asunto(s)
Mucor , Carne de Cerdo , Carne Roja , Porcinos , Animales , Papaína , Ácidos Grasos Insaturados , Ácido Linoleico , Oxígeno
9.
Artículo en Inglés | MEDLINE | ID: mdl-38185464

RESUMEN

In the oleaginous fungus Mucor circinelloides, lipid accumulation is regulated by nitrogen metabolism, which is regulated by the areA gene, a member of the GATA zinc finger transporter family and a major regulator for nitrogen metabolism. However, the role of areA in lipid accumulation in this fungus has not been reported. In order to explore the regulatory effect of areA gene on nitrogen metabolism and lipid accumulation in M. circinelloides, we constructed areA gene knockout and overexpression strains. Then, the recombinant strains were cultured and their biochemical indexes were measured. Simultaneously, transcriptomic studies on the recombinant strains were conducted to infer the regulatory mechanism of areA. The results showed that the areA knockout strain accumulated more lipid, which is 42 % higher than the control. While the areA overexpressing strain obtained the higher biomass accumulation (23 g/L) and used up the nitrogen source in the medium earlier than the control strain and knockout strain. Transcriptome data analysis showed that nr and nit-6 genes related to nitrogen metabolism were up-regulated. And the expression levels of key genes acc and aclY were higher in the areA knockout strain than others, which was positively correlated with the increased lipid accumulation. In addition, in knockout strains, protein catabolism tended to provide substrates for the lipid production, and the expression levels of the related genes were also higher than others. These results indicated that the areA gene not only controls the transcription level of genes related to nitrogen metabolism but also affects lipid accumulation.


Asunto(s)
Metabolismo de los Lípidos , Mucor , Metabolismo de los Lípidos/genética , Mucor/genética , Mucor/metabolismo , Lípidos , Nitrógeno/metabolismo
10.
Sci Rep ; 14(1): 806, 2024 01 08.
Artículo en Inglés | MEDLINE | ID: mdl-38191628

RESUMEN

Layered double hydroxides have recently gained wide interest as promising multifunctional nanomaterials. In this work, a multifunctional ternary Zn-Co-Fe LDH was prepared and characterized using XRD, FTIR, BET, TEM, SEM, and EDX. This LDH showed a typical XRD pattern with a crystallite size of 3.52 nm and a BET surface area of 155.9 m2/g. This LDH was investigated, for the first time, as an adsorbent for moxifloxacin, a common fluoroquinolones antibiotic, showing a maximum removal efficiency and equilibrium time of 217.81 mg/g and 60 min, respectively. Its antifungal activity, for the first time, was investigated against Penicillium notatum, Aspergillus flavus, Aspergillus fumigatus, Aspergillus niger, and Mucor fungi at various concentrations (1000-1.95 µg/mL). This LDH was found to be effective against a variety of fungal strains, particularly Penicillium and Mucor species and showed zones of inhibition of 19.3 and 21.6 mm for Penicillium and Mucor, respectively, with an inhibition of 85% for Penicillium species and 68.3% for Mucormycosis. The highest antifungal efficacy results were obtained at very low MIC concentrations (33.3 and 62 µg/ml) against Penicillium and Mucor, respectively. The results of this study suggest a promising multifunctional potential of this LDH for water and wastewater treatment and disinfection applications.


Asunto(s)
Antifúngicos , Penicillium , Antifúngicos/farmacología , Moxifloxacino/farmacología , Desinfección , Hidróxidos , Mucor , Zinc
11.
Artículo en Inglés | MEDLINE | ID: mdl-38052250

RESUMEN

Lipid biosynthesis is a significant metabolic response to nitrogen starvation in oleaginous fungi. The oleaginous fungus Mucor circinelloides copes with nitrogen stress by degrading AMP through AMP deaminase (AMPD). However, the mechanism of AMPD in regulating lipogenesis remains largely unclear. To elucidate the mechanism of AMPD in lipid synthesis in this M. circinelloides, we identified two genes (ampd1 and ampd2) encoding AMPD and constructed an ampd double knockout mutant. The engineered M. circinelloides strain elevated cell growth and lipid accumulation, as well as the content of oleic acid (OA) and gamma-linolenic acid (GLA). In addition to the expected increase in transcription levels of genes associated with lipid and TAG synthesis, we observed suppression of lipid degradation and reduced amino acid biosynthesis. This suggested that the deletion of AMPD genes induces the redirection of carbon towards lipid synthesis pathways. Moreover, the pathways related to nitrogen metabolism, including nitrogen assimilation and purine metabolism (especially energy level), were also affected in order to maintain homeostasis. Further analysis discovered that the transcription factors (TFs) related to lipid accumulation were also regulated. This study provides new insights into lipid biosynthesis in M. circinelloides, indicating that the trigger for lipid accumulation is not entirely AMPD-dependent and suggest that there may be additional mechanisms involved in the initiation of lipogenesis.


Asunto(s)
AMP Desaminasa , Metabolismo de los Lípidos , Mucor , Metabolismo de los Lípidos/genética , AMP Desaminasa/genética , AMP Desaminasa/metabolismo , Nitrógeno/metabolismo , Lípidos
12.
O.F.I.L ; 34(1): 92-94, 2024.
Artículo en Español | IBECS | ID: ibc-232632

RESUMEN

El tratamiento de las infecciones fúngicas invasivas, tanto la aspergilosis invasora como la mucormicosis supone un importante desafío clínico por el reducido número de agentes antifúngicos azólicos disponibles y por la gravedad clínica. Debido a esta elevada mortalidad, es necesario un diagnóstico temprano y un tratamiento agresivo, no sólo debe ser médico sino también quirúrgico. Presentamos un caso de mucormicosis maxilofacial en un paciente sin antecedentes clínicos de interés. Se trata de un paciente de 40 años con bultoma en región submandibular derecha de aparición más o menos súbita. Refiere parestesias en labio inferior hemilabio derecho con desviación del mismo a la derecha, de un año. Extracción del molar sin complicaciones aparentes. Los resultados de la primera biopsia muestran tejidos blandos con microorganismos micóticos compatibles con mucormicosis. En la exploración clínica se palpa inflamación a nivel de la zona submandibular derecha, no dolorosa. Resto: buen estado general. Comienza tratamiento con fluconazol, y posteriormente con isavuconazol durante 43 días. Los resultados de la segunda biopsia (junio-21): proceso linfoproliferativo B de alto grado compatible con linfoma difuso de células grandes B de centro germinal. Se realiza PET/TC compatible con infiltración ganglionar laterocervical derecha alta y submentoniana con probable afectación de partes blandas y más dudosa amigdalar palatina bilateral de su proceso linfoproliferativo de base. En enero-22: estudio PET/CT que muestra respuesta metabólica completa (Deauville 1) de su proceso linfoproliferativo de base. (AU)


The treatment of invasive fungal infections, both invasive aspergillosis and mucormycosis, represents an important clinical challenge due to the small number of available azole antifungal agents and the clinical severity. Due to this high mortality, early diagnosis and aggressive treatment are necessary, not only medical but also surgical. We present a case of maxillofacial mucormycosis in a patient with no clinical history of interest. This is a 40-year-old patient with a lump in the right submandibular region of more or less sudden onset. Refers paresthesias in the lower lip right hemilip with deviation of the same to the right of a year. Molar extraction without apparent complications. The results of the first biopsy show soft tissues with fungal organisms consistent with mucormycosis. In the clinical examination, inflammation was palpated at the level of the right submandibular area, which was not painful. Rest: good general condition. He begins treatment with fluconazole, and later with isavuconazole for 43 days. The results of the second biopsy (June 21): high-grade B-lymphoproliferative process compatible with diffuse large B-cell lymphoma of the germinal center. PET/CT compatible with high right laterocervical and submental lymph node infiltration with probable soft tissue involvement and more doubtful bilateral palatine tonsillar involvement of its underlying lymphoproliferative process was performed. On January-22: PET/CT study showing complete metabolic response (Deauville 1) of his underlying lymphoproliferative process. (AU)


Asunto(s)
Humanos , Adulto , Mucormicosis , Rhizopus , Mucor , Anfotericina B , Cirugía General
13.
Curr Microbiol ; 81(1): 47, 2023 Dec 22.
Artículo en Inglés | MEDLINE | ID: mdl-38135799

RESUMEN

Mucormycosis is uncommon, yet it is more prevalent among individuals with underlying health conditions and those who are immunocompromised. Chitosan is studied because of its appealing properties and diverse applications. The purpose of this work is to synthesize chitosan nanoparticles (CSNPs) by ionic gelation method at various pH levels and test them against Mucor and other filamentous fungus. Field Emission Scanning Electron Microscope, Zeta sizer, Zeta potential, and Fourier Transformed Infrared Spectroscopy were used to characterize CSNPs. Hydrodynamic size increased considerably with increasing pH. Our CSNPs were tested against fungal isolates of Aspergillus Flavus RCMB 02783, Aspergillus Fumigatus RCMB 02564, and Aspergillus Niger RCMB 02588, Penicillium Notatum (NCPF 2881) and   (M. circinelloides CNRMA 03.894) causing mucromycosis. Antifungal activity was investigated using Minimum inhibitory concentration (MIC), Minimum Fungicidal concentration (MFC), Disc diffusion assay, and Antifungal inhibitory percentages methods. The best antifungal efficacy results were obtained through CSNPs prepared at pH = 4.4 at very low concentration for MIC (1.03 or 2.75 µg/mL) with 100% M. circinelloides inhibition followed by pH = 4.6 with MIC (73 or 208 µg/mL) and 93%  M. cirecinelloides inhibition %. Future usage of these materials in masks or wound dressing to avoid fungal infections, including mucormycosis following COVID-19, penicillium, and aspergillosis toxicity and infections.


Asunto(s)
Quitosano , Mucormicosis , Nanopartículas , Penicillium chrysogenum , Humanos , Antifúngicos/farmacología , Mucormicosis/tratamiento farmacológico , Mucormicosis/microbiología , Mucor , Quitosano/farmacología , Aspergillus niger , Pruebas de Sensibilidad Microbiana , Concentración de Iones de Hidrógeno
14.
J Microbiol ; 61(12): 1043-1062, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38114662

RESUMEN

Mucormycosis is a lethal and difficult-to-treat fungal infection caused by fungi of the order Mucorales. Mucor lusitanicus, a member of Mucorales, is commonly used as a model to understand disease pathogenesis. However, transcriptional control of hyphal growth and virulence in Mucorales is poorly understood. This study aimed to investigate the role of Tec proteins, which belong to the TEA/ATTS transcription factor family, in the hyphal development and virulence of M. lusitanicus. Unlike in the genome of Ascomycetes and Basidiomycetes, which have a single Tec homologue, in the genome of Mucorales, two Tec homologues, Tec1 and Tec2, were found, except in that of Phycomyces blakesleeanus, with only one Tec homologue. tec1 and tec2 overexpression in M. lusitanicus increased mycelial growth, mitochondrial content and activity, expression of the rhizoferrin synthetase-encoding gene rfs, and virulence in nematodes and wax moth larvae but decreased cAMP levels and protein kinase A (PKA) activity. Furthermore, tec1- and tec2-overexpressing strains required adequate mitochondrial metabolism to promote the virulent phenotype. The heterotrimeric G beta subunit 1-encoding gene deletant strain (Δgpb1) increased cAMP-PKA activity, downregulation of both tec genes, decreased both virulence and hyphal development, but tec1 and tec2 overexpression restored these defects. Overexpression of allele-mutated variants of Tec1(S332A) and Tec2(S168A) in the putative phosphorylation sites for PKA increased both virulence and hyphal growth of Δgpb1. These findings suggest that Tec homologues promote mycelial development and virulence by enhancing mitochondrial metabolism and rhizoferrin accumulation, providing new information for the rational control of the virulent phenotype of M. lusitanicus.


Asunto(s)
Mucor , Factores de Transcripción , Factores de Transcripción/genética , Virulencia/genética , Estrés Oxidativo , Proteínas Fúngicas/genética
15.
J Agric Food Chem ; 71(42): 15680-15691, 2023 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-37822229

RESUMEN

Lipid accumulation in oleaginous organisms is initiated by AMP deaminase (AMPD) after nitrogen depletion because it mediates the concentration of intracellular adenosine monophosphate (AMP). However, the role of AMPD in lipogenesis in the oleaginous fungus Mucor circinelloides is largely unknown. Therefore, we identified the genes (ampd1 and ampd2) encoding AMPD and investigated the role of AMPD in lipid synthesis in this fungus by overexpressing and deleting ampd genes. Deletion of ampd1 and ampd2 caused 21 and 28% increments in lipid contents under N-limited conditions, respectively. These increases were correlated with the activation of enzymes involved in lipogenesis and the alteration of energy balance. Unexpectedly, overexpression of ampd genes affected nitrogen consumption in both N-limited and N-excess media, which resulted in an increase in cell growth and lipid accumulation compared with the control strain when nitrogen was available. Furthermore, the increased lipid accumulation in the ampd-overexpressing mutants in N-excess media was accompanied by enhanced activities of lipid biosynthetic enzymes. These data suggested that nitrogen metabolism and energy metabolism are affected by AMPD, and overexpression of ampd genes induced lipid accumulation under nitrogen-rich conditions by mimicking the nitrogen limitation response. This highlights an intriguing function of AMPD in M. circinelloides.


Asunto(s)
AMP Desaminasa , Lipogénesis , Metabolismo de los Lípidos , AMP Desaminasa/genética , AMP Desaminasa/metabolismo , Mucor/genética , Mucor/metabolismo , Lípidos , Nitrógeno/metabolismo
16.
Med. infant ; 30(3): 263-269, Septiembre 2023. tab
Artículo en Español | LILACS, UNISALUD, BINACIS | ID: biblio-1515961

RESUMEN

Los estudios sobre la infección fúngica invasiva (IFI) por Mucor spp. en pacientes pediátricos con patología hematooncológica, son de baja solidez científica, lo que dificulta conocer en profundidad sus características y evolución. Con el objetivo de analizar la evolución fatal de esos pacientes, se llevó a cabo esta revisión sistemática (RS). Material y métodos: La búsqueda bibliográfica se realizó con fecha 23 de marzo de 2023, en las principales bases de datos (Medline (a través de Pubmed), Embase (a través de Embase-Elsevier), The Cochrane Library (a través de Wiley), Cinahl (a través de Ebsco HOST), SCI-EXPANDED, SciELO (a través de la WOS) y Scopus (a través de Scopus-Elsevier), libre (mediante el motor Google) y revisando las citas de los artículos incluidos. Resultados: Se rescataron 1393 artículos, de los cuales se descartaron 1386 por diversas razones. Mediante el análisis de los textos completos, finalmente se incluyeron 7 estudios. Todos los estudios eran series de casos (nivel 4). La mediana de la frecuencia de muerte observada fue de 36,6% (Q1 20% - Q347%). Conclusiones: Esta RS mostró en niños con patología hemato-oncológica, que la mortalidad por IFI por Mucor spp. alcanzó a casi un tercio de los pacientes (AU)


Studies on invasive fungal infection (IFI) by Mucor spp. in pediatric patients with cancer have a low level of evidence, which makes it difficult to elucidate its characteristics and progression. To analyze the fatal outcome of these patients, this systematic review (SR) was conducted. Material and methods: A literature search was carried out on March 23, 2023, in the following main databases (Medline (via Pubmed), Embase (via Embase-Elsevier), The Cochrane Library (via Wiley), Cinahl (via Ebsco HOST), SCI-EXPANDED, SciELO (via the WOS) and Scopus (via Scopus-Elsevier). Additionally, a complementary search was carried out using free search engines (such as Google) and by reviewing the references of the included articles. Results: A total of 1393 articles were retrieved, of which 1386 were excluded for various reasons. After a thorough analysis of the full-text articles, 7 studies were ultimately included in the review. All studies were case series (level 4). The median observed death rate was 36.6% (IQR, 20% - 47%). Conclusions: This SR showed that in children with hematological-oncological disease, mortality due to IFI by Mucor spp. affected almost one third of the patients (AU)


Asunto(s)
Humanos , Niño , Adolescente , Infecciones Oportunistas/microbiología , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/mortalidad , Neoplasias Hematológicas/terapia , Infecciones Fúngicas Invasoras/tratamiento farmacológico , Mucormicosis/diagnóstico , Mucormicosis/tratamiento farmacológico , Antifúngicos/uso terapéutico , Factores de Riesgo , Huésped Inmunocomprometido , Mucor , Neutropenia
17.
Mycologia ; 115(5): 674-692, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37409884

RESUMEN

Mucor species are a group of common soil-borne fungi, known to cause infections on humans and animals, interfere in food production, and act as useful agents in biotechnological applications. This study reports one new Mucor species, M. yunnanensis, which was found to be fungicolous on an Armillaria sp. from southwest China. Further, M. circinelloides on Phlebopus sp., M. hiemalis on Ramaria sp. and Boletus sp., M. irregularis on Pleurotus sp., M. nederlandicus on Russula sp., and M. yunnanensis on Boletus sp. are reported as new host records. Mucor yunnanensis and M. hiemalis have been collected from Yunnan Province in China, whereas M. circinelloides, M. irregularis, and M. nederlandicus have been collected from Chiang Mai and Chiang Rai Provinces in Thailand. All the Mucor taxa reported herein were identified based on both morphology and phylogenetic analyses of a combined nuc rDNA internal transcribed spacer region ITS1-5.8S-ITS2 (ITS) and partial nuc 28S rDNA (28S) sequence matrix. Comprehensive descriptions, illustrations, and a phylogenetic tree are provided for all the taxa reported in the study to show the placements of taxa, and the new taxon is compared with its sister taxa.


Asunto(s)
Agaricales , Ascomicetos , Basidiomycota , Animales , Humanos , Agaricales/genética , China , Filogenia , ADN Espaciador Ribosómico/genética , Mucor/genética , Tailandia , ARN Ribosómico 28S/genética , ADN Ribosómico/genética , Basidiomycota/genética , Análisis de Secuencia de ADN
18.
J Appl Genet ; 64(3): 569-590, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37407883

RESUMEN

Among ten metal-tolerant fungal isolates obtained from the microbiomes of detergent industry effluent, Mucor sp. NRCC6 showed the highest tolerance and an adaptive behavior toward the heavy metals Ni2+, Pb2+, Mn2+, and Zn2+. It gave the highest growth rates 0.790 ± 0.59, 0.832 ± 0.32, 0.774 ± 0.40, and 0.741 ± 1.06 mm/h along with the lowest growth inhibition 9.19, 4.37, 11.04, and 14.83% in the presence of Pb2+, Zn2+, Ni2+, and Mn2+, respectively, at a concentration of 5.0 g/L. Then, Mucor sp. NRCC6 was selected as a biotrap for the removal of these heavy metals. The optimized operating conditions were detected to be pH 6.0 for Pb2+, Zn2+, and Mn2+ and pH 5.5 for Ni2+ at 30 °C; agitation speed 150 rpm; contact time 30 min for Mn2+ and Ni2+, 30-60 min for Pb2+, and 90-180 min for Zn2+; NRCC6 biomass dosage 5.0 g/L for Ni2+ and Pb2+ and 10.0 g/L for Mn2+ and Zn2+; and initial concentration 12 mg/L of each ion in the multimetal aqueous solutions. Under these optimized conditions, the adsorption capacity for Pb2+, Ni2+, Mn2+, and Zn2+ reached 98.75, 59.25, 58.33, and 50.83%. The Langmuir isotherm was the best for describing the adsorption of Zn2+ (0.970) and Mn2+ (0.977). The Freundlich isotherm significantly giving a good fit to the adsorption of Pb2+ (0.998) while the adsorption of Ni2+ onto NRCC6 biomass can follow DKR (0.998). Furthermore, the current study revealed that Mucor sp. NRCC6 fungus is a new efficient and eco-friendly method that revealed a maximum removal of 100% for Pb2+ and Zn2+ as well as 97.39, 88.70, 78.95, 74.0, 70.22, 68.57, and 60.0% for Ni2+, Mn2+, Cd2+, Cu2+, Fe3+, As2+, and Cr6+ from the industrial wastewater, respectively.


Asunto(s)
Metales Pesados , Mucor , Detergentes , Biodegradación Ambiental , Biomasa , Plomo , Metales Pesados/análisis , Agua
19.
Environ Sci Pollut Res Int ; 30(41): 93846-93861, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37523087

RESUMEN

Bioremediation of toxic metals is a feasible and low-cost remediation tool to reduce metal contamination. Plant-fungus interactions can improve this technique. Eichhornia crassipes (Mart.) Solms is a macrophyte reported to bioremediate contaminated water. Thus, the present study aimed to isolate endophytic fungi from E. crassipes, select a highly cadmium (Cd) tolerant isolate and evaluate its bioremediation potential. This was evaluated by (1) the fungus tolerance and capacity to accumulate Cd; (2) Cd effects on cell morphology (using SEM and TEM) and on the fungal antioxidant defense system, as well as (3) the effect on model plant Solanum lycopersicum L. cultivar Calabash Rouge, inoculated with the endophyte fungus and exposed to Cd. Our results selected the endophyte Mucor sp. CM3, which was able to tolerate up to 1000 g/L of Cd and to accumulate 900 mg of Cd/g of biomass. Significant changes in Mucor sp. CM3 morphology were observed when exposed to high Cd concentrations, retaining this metal both in its cytoplasm and in its cell wall, which may be linked to detoxification and metal sequestration mechanisms related to the formation of Cd-GSH complexes. In addition, Cd stress induced the activation of all tested antioxidant enzymes - superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GR) - in this endophytic fungus. Moreover, when inoculated in tomato plants, this fungus promoted plant growth (in treatments without Cd) and induced an increased metal translocation to plant shoot, showing its potential to increase metal bioremediation. Therefore, this study indicates that the isolated endophyte Mucor sp. CM3 can be applied as a tool in different plant conditions, improving plant bioremediation and reducing the environmental damage caused by Cd, while also promoting plant growth in the absence of contaminants.


Asunto(s)
Eichhornia , Contaminantes del Suelo , Cadmio/toxicidad , Antioxidantes/farmacología , Mucor , Biodegradación Ambiental , Metales/farmacología , Endófitos , Contaminantes del Suelo/análisis
20.
Plant Dis ; 107(11): 3602-3607, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37272052

RESUMEN

Mucor rot caused by Mucor piriformis is an emerging postharvest disease of mandarin fruit in California. Natamycin is a newly registered biofungicide for postharvest use on citrus and some other fruits. In the study, baseline sensitivity to natamycin in 50 isolates of M. piriformis was determined in vitro. The mean EC50 (effective concentration to inhibit sporangiospore germination by 50%) and MIC (minimum inhibitory concentration to inhibit mycelial growth by 100%) values were 0.59 µg/ml and less than 1.0 µg/ml, respectively. Natamycin at the label rate of 920 µg/ml alone or in combination with 3% potassium sorbate (PS) or 3% sodium carbonate (SC) applied at 20 or 50°C was evaluated for control of Mucor rot on inoculated 'Tango' mandarin fruit. Natamycin alone reduced Mucor rot incidence on stored mandarin fruit from 100% among nontreated control fruit to approximately 30%, a reduction of more than 70% compared to the nontreated control, while 3% PS and 3% SC had no to little control. When applied at 50°C, natamycin and 3% PS reduced Mucor rot incidence by 65.0 and 31.2%, respectively; while natamycin in combination with 3% PS reduced disease incidence by 92.5% compared to the nontreated control after 2 weeks of storage at 5°C. This combined treatment remained effective even when the application of the treatment was delayed for 6 and 12 h after inoculation. However, the effectiveness of the treatments declined when storage was extended to 3 or 4 weeks. Natamycin can be an effective tool to control Mucor rot on mandarin fruit, and minimizing the period of extended storage could help maintain the control efficacy of natamycin.


Asunto(s)
Frutas , Natamicina , Natamicina/farmacología , Mucor , Calor
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