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1.
Food Chem ; 455: 139874, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-38838624

RESUMO

Molecules of natural origin often possess useful biological activities. For instance, the natural peptide Tilapia Piscidin 4 (TP4) exhibits potent antimicrobial activity against a broad spectrum of pathogens. In this study, we explored the potential application of TP4 as a food preservative, asking whether it can prevent spoilage due to microbial contamination. A preliminary in silico analysis indicated that TP4 should interact strongly with fungal cell membrane components. Hence, we tested the activity of TP4 toward Candida albicans within fruit juice and found that the addition of TP4 could abolish fungal growth. We further determined that the peptide acts via a membranolytic mechanism and displays concentration-dependent killing efficiency. In addition, we showed that TP4 inhibited growth of Rhizopus oryzae in whole fruit (tomato) samples. Based on these findings, we conclude that TP4 should be further evaluated as a potentially safe and green solution to prevent food spoilage.


Assuntos
Candida albicans , Conservantes de Alimentos , Rhizopus , Animais , Candida albicans/efeitos dos fármacos , Rhizopus/efeitos dos fármacos , Rhizopus/crescimento & desenvolvimento , Conservantes de Alimentos/farmacologia , Conservantes de Alimentos/química , Tilápia/microbiologia , Tilápia/crescimento & desenvolvimento , Proteínas de Peixes/farmacologia , Proteínas de Peixes/química , Conservação de Alimentos/métodos , Contaminação de Alimentos/prevenção & controle , Contaminação de Alimentos/análise , Antifúngicos/farmacologia , Antifúngicos/química , Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/química
2.
mBio ; 15(7): e0116624, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-38934618

RESUMO

Contemporary antifungal therapies utilized to treat filamentous fungal infections are inhibited by intrinsic and emerging drug resistance. Consequently, there is an urgent need to develop novel antifungal compounds that are effective against drug-resistant filamentous fungi. Here, we utilized an Aspergillus fumigatus cell-based high-throughput screen to identify small molecules with antifungal activity that also potentiated triazole activity. The screen identified 16 hits with promising activity against A. fumigatus. A nonspirocyclic piperidine, herein named MBX-7591, exhibited synergy with triazole antifungal drugs and activity against pan-azole-resistant A. fumigatus isolates. MBX-7591 has additional potent activity against Rhizopus species and CO2-dependent activity against Cryptococcus neoformans. Chemical, genetic, and biochemical mode of action analyses revealed that MBX-7591 increases cell membrane saturation by decreasing oleic acid content. MBX-7591 has low toxicity in vivo and shows good efficacy in decreasing fungal burden in a murine model of invasive pulmonary aspergillosis. Taken together, our results suggest MBX-7591 is a promising hit with a novel mode of action for further antifungal drug development to combat the rising incidence of triazole-resistant filamentous fungal infections.IMPORTANCEThe incidence of infections caused by fungi continues to increase with advances in medical therapies. Unfortunately, antifungal drug development has not kept pace with the incidence and importance of fungal infections, with only three major classes of antifungal drugs currently available for use in the clinic. Filamentous fungi, also called molds, are particularly recalcitrant to contemporary antifungal therapies. Here, a recently developed Aspergillus fumigatus cell reporter strain was utilized to conduct a high-throughput screen to identify small molecules with antifungal activity. An emphasis was placed on small molecules that potentiated the activity of contemporary triazole antifungals and led to the discovery of MBX-7591. MBX-7591 potentiates triazole activity against drug-resistant molds such as A. fumigatus and has activity against Mucorales fungi. MBX-7591's mode of action involves inhibiting the conversion of saturated to unsaturated fatty acids, thereby impacting fungal membrane integrity. MBX-7591 is a novel small molecule with antifungal activity poised for lead development.


Assuntos
Antifúngicos , Aspergillus fumigatus , Farmacorresistência Fúngica , Ácidos Graxos Insaturados , Testes de Sensibilidade Microbiana , Triazóis , Aspergillus fumigatus/efeitos dos fármacos , Aspergillus fumigatus/genética , Antifúngicos/farmacologia , Triazóis/farmacologia , Camundongos , Animais , Ácidos Graxos Insaturados/farmacologia , Humanos , Ensaios de Triagem em Larga Escala , Sinergismo Farmacológico , Rhizopus/efeitos dos fármacos , Rhizopus/genética , Cryptococcus neoformans/efeitos dos fármacos , Cryptococcus neoformans/genética , Piperidinas/farmacologia , Modelos Animais de Doenças , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Aspergilose Pulmonar Invasiva/microbiologia
3.
Antimicrob Agents Chemother ; 68(5): e0154523, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38557112

RESUMO

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.


Assuntos
Anfotericina B , Antifúngicos , Glicosídeos , Mucormicose , Neutropenia , Triterpenos , Animais , Anfotericina B/uso terapêutico , Anfotericina B/farmacologia , Mucormicose/tratamento farmacológico , Camundongos , Antifúngicos/uso terapêutico , Antifúngicos/farmacologia , Triterpenos/farmacologia , Triterpenos/uso terapêutico , Neutropenia/tratamento farmacológico , Neutropenia/complicações , Modelos Animais de Doenças , Quimioterapia Combinada , Feminino , Rhizopus/efeitos dos fármacos , Pneumopatias Fúngicas/tratamento farmacológico , Pneumopatias Fúngicas/microbiologia , Mucor/efeitos dos fármacos , Triazóis/uso terapêutico , Triazóis/farmacologia
4.
Eur J Med Res ; 26(1): 131, 2021 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-34775981

RESUMO

BACKGROUND: Mucormycosis is a rare fungal infection occurring chiefly in the lung or the rhino-orbital-cerebral compartment, particularly in patients with immunodeficiency or diabetes mellitus. Among Mucorales fungi, Rhizopus spp. are the most common cause of mucormycosis. CASE PRESENTATION: We report a case of pulmonary mucormycosis caused by Rhizopus microsporus in a young patient with diabetes but no other apparent risk factors. The diagnosis mainly relied on clinical manifestation, positive pulmonary tissue biopsy, and fungal culture. The patient was successfully treated with posaconazole oral suspension and remains asymptomatic at one-year follow-up. CONCLUSIONS: Pulmonary mucormycosis is a life-threatening condition and posaconazole is an effective treatment for pulmonary mucormycosis caused by Rhizopus microspores.


Assuntos
Pneumopatias/tratamento farmacológico , Pulmão/efeitos dos fármacos , Mucormicose/tratamento farmacológico , Rhizopus/efeitos dos fármacos , Triazóis/uso terapêutico , Adulto , Antifúngicos/uso terapêutico , Humanos , Pulmão/microbiologia , Pulmão/patologia , Pneumopatias/microbiologia , Masculino , Mucormicose/microbiologia , Rhizopus/fisiologia , Resultado do Tratamento
5.
Mycoses ; 64(7): 780-787, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33835599

RESUMO

BACKGROUND: Mucorales are opportunistic pathogens that can cause life-threatening diseases predominantly in immunocompromised patients. OBJECTIVES: This study aimed to investigate the frequency, seasonal variation and antifungal susceptibility of pathogenic Mucorales in the soil collected from seven hospitals in Urmia, Iran, between November 2017 and July 2018 in four different seasons. METHODS: Mucorales isolates obtained from soil were characterised based on conventional and molecular assays. In addition, in vitro antifungal susceptibility was performed using the CLSI M38Ed3 procedure. RESULTS: Out of 196 tested soil samples, 80 (40.8%) samples were positive for mucoralean fungi. Rhizopus arrhizus var. arrhizus (n = 47) was the most frequent species followed by Mucor circinelloides (n = 21) and Cunninghamella echinulata (n = 6). A seasonal variation in the frequency of Mucorales in soil was detected with a maximum of culture-positive soil samples detected in wet autumn (43.2%) followed by winter (23.4%), summer (19.7%) and spring (13.6%). In vitro antifungal susceptibility testing for 80 environmental isolates exhibited MIC of ≤2 µg/ml for amphotericin B indicating the smallest range of MIC variation among the tested Mucorales (range: 0.125-2 µg/ml). Among the azoles, posaconazole was the most effective antifungals (GM MIC, 0.724 µg/ml). CONCLUSIONS: We considered associations of species and seasonal frequencies between soil mucoralean fungi and mucormycosis. The effect of opportunistic Mucorales dominating in the soil and prevalent causative agents of mucormycosis in Iran reported in the literatures but more comprehensive studies are needed to confirm this conclusion.


Assuntos
Mucorales , Anfotericina B/farmacologia , Antifúngicos/farmacologia , Cunninghamella/efeitos dos fármacos , Cunninghamella/isolamento & purificação , Hospitais , Humanos , Irã (Geográfico) , Testes de Sensibilidade Microbiana , Mucor/efeitos dos fármacos , Mucor/isolamento & purificação , Mucorales/efeitos dos fármacos , Mucorales/isolamento & purificação , Mucormicose/transmissão , Infecções Oportunistas/transmissão , Rhizopus/efeitos dos fármacos , Rhizopus/isolamento & purificação , Estações do Ano , Solo , Microbiologia do Solo , Triazóis/farmacologia
6.
Molecules ; 26(8)2021 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-33919567

RESUMO

Essential oils are gaining interest as environmentally friendly alternatives to synthetic fungicides for management of seedborne pathogens. Here, seven essential oils were initially tested in vivo for disinfection of squash seeds (Cucurbita maxima) naturally contaminated by Stagonosporopsis cucurbitacearum, Alternaria alternata, Fusarium fujikuro, Fusarium solani, Paramyrothecium roridum, Albifimbria verrucaria, Curvularia spicifera, and Rhizopus stolonifer. The seeds were treated with essential oils from Cymbopogon citratus, Lavandula dentata, Lavandula hybrida, Melaleuca alternifolia, Laurus nobilis, and Origanum majorana (#1 and #2). Incidence of S. cucurbitacearum was reduced, representing a range between 67.0% in L. nobilis to 84.4% in O. majorana #2. Treatments at 0.5 mg/mL essential oils did not affect seed germination, although radicles were shorter than controls, except with C. citratus and O. majorana #1 essential oils. Four days after seeding, seedling emergence was 20%, 30%, and 10% for control seeds and seeds treated with C. citratus essential oil (0.5 mg/mL) and fungicides (25 g/L difenoconazole plus 25 g/L fludioxonil). S. cucurbitacearum incidence was reduced by ~40% for plantlets from seeds treated with C. citratus essential oil. These data show the effectiveness of this essential oil to control the transmission of S. cucurbitacearum from seeds to plantlets, and thus define their potential use for seed decontamination in integrated pest management and organic agriculture.


Assuntos
Cucurbita/microbiologia , Óleos Voláteis/farmacologia , Óleos de Plantas/farmacologia , Sementes/efeitos dos fármacos , Alternaria/efeitos dos fármacos , Alternaria/patogenicidade , Ascomicetos/patogenicidade , Cucurbita/efeitos dos fármacos , Curvularia/efeitos dos fármacos , Curvularia/patogenicidade , Fungicidas Industriais/química , Fungicidas Industriais/farmacologia , Fusarium/efeitos dos fármacos , Fusarium/patogenicidade , Hypocreales/efeitos dos fármacos , Hypocreales/patogenicidade , Óleos Voláteis/química , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Óleos de Plantas/química , Rhizopus/efeitos dos fármacos , Rhizopus/patogenicidade , Sementes/microbiologia
7.
J Sci Food Agric ; 101(1): 229-239, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32627181

RESUMO

BACKGROUND: Synthetic fungicides are most commonly used for controlling postharvest disease of fruit, although they can cause the emergence of drug-resistant strains, environmental pollution and fruit safety issues. Bacillomycin D (BD), a novel antifungal lipopeptide, and chitosan (CTS) are applied for the preservation of cherry tomato. RESULTS: The combination of BD and CTS showed an additive inhibition on the growth of Rhizopus stolonifer and Botrytis cinerea compared to that of its individual compound. In addition, BD + CTS reduced the incidence of soft rot and gray mold in cherry tomato caused by R. stolonifer and B. cinerea, respectively. Tomato treated with BD + CTS exhibited a lower weight loss and higher firmness and higher contents of total soluble solids, titratable acidity and ascorbic acid compared to those treated with sterile water (control). The kinetics models demonstrated that the shelf life of cherry tomato treated with BD + CTS could be extended by approximately 15 days longer than the control. CONCLUSION: The utilization of BD + CTS provided a novel strategy for reducing postharvest fungal rot and maintaining the storage quality of cherry tomato. © 2020 Society of Chemical Industry.


Assuntos
Peptídeos Catiônicos Antimicrobianos/farmacologia , Botrytis/efeitos dos fármacos , Quitosana/farmacologia , Conservação de Alimentos/métodos , Fungicidas Industriais/farmacologia , Rhizopus/efeitos dos fármacos , Solanum lycopersicum/microbiologia , Botrytis/crescimento & desenvolvimento , Sinergismo Farmacológico , Frutas/química , Frutas/microbiologia , Solanum lycopersicum/química , Doenças das Plantas/microbiologia , Rhizopus/crescimento & desenvolvimento
8.
J Appl Microbiol ; 130(6): 1993-2007, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33190384

RESUMO

AIMS: With a goal to identify specific essential oils that can control postharvest Rhizopus rot on strawberry and peach fruits, we performed screening for 26 essential oils based on their antifungal activity against Rhizopus stolonifer in vitro and investigated the underlying mechanism. METHODS AND RESULTS: Mentha spicata (Ms), Mentha piperita (Mp), Thymus vulgaris CT carvacrol (Tc) and Thymus vulgaris CT thymol (Tt) exhibited strong inhibition on R. stolonifer growth in the screening. These essential oils increased plasma membrane permeability of R. stolonifer and resulted in the outflow of intercellular electrolyte, nucleic acid, protein and soluble sugar. Morphology of R. stolonifer mycelia was greatly altered by these essential oils. Hyphae treated by these essential oils exhibited high accumulation of superoxide anion and malonaldehyde. Combination of these essential oils in commercial package reduced Rhizopus rot on strawberry and peach fruits, with Mp showing the strongest efficiency. CONCLUSION: Ms, Mp, Tc and Tt essential oils inhibited R. stolonifer growth by targeting its plasma membrane and reduced Rhizopus rot on strawberry and peach fruits. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides potential applications of natural plant extract, as alternatives to tradition fungicides, to control postharvest decay on fruits and vegetables.


Assuntos
Conservação de Alimentos/métodos , Mentha/química , Óleos Voláteis/farmacologia , Rhizopus/efeitos dos fármacos , Thymus (Planta)/química , Permeabilidade da Membrana Celular/efeitos dos fármacos , Fragaria/microbiologia , Frutas/microbiologia , Fungicidas Industriais/farmacologia , Hifas/efeitos dos fármacos , Hifas/crescimento & desenvolvimento , Hifas/metabolismo , Prunus persica/microbiologia , Rhizopus/crescimento & desenvolvimento , Rhizopus/metabolismo
9.
Mol Biol Rep ; 47(9): 6657-6668, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32794133

RESUMO

This study attempted to characterize the involvement of a change in the redox status and subcellular localization in the BABA-induced priming resistance of peach fruit against Rhizopus rot. Specifically, 50 mM BABA primed the peaches for the enhanced disease resistance against R. stolonifer, as demonstrated by suppression of the disease development upon pathogen challenge accompanied by the clearly elevated level of TGA transcription factor (PpTGA1) and NPR1 gene (PpNPR1). In addition, the BABA elicitation enhanced the activities of a series of critical enzymes in the PPP and AsA-GSH cycle, and eventually promoted the NADPH and GSH pools, which altered the intracellular redox state towards a highly reductive condition. Additionally, PpTGA1-GFP was localized in the cytoplasm in the absence of BABA treatment or R. stolonifer inoculation, while BABA elicitation plus R. stolonifer inoculation caused PpTGA1-GFP to specifically translocate to the nucleus, where it interacted with PpNPR1 and regulated the positive expression of PR genes. Therefore, the observations implied that BABA could promote the reduction of the redox state, resulting in the translocation of PpTGA1 to the nucleus, which was a prerequisite for the induction of a priming defence against Rhizopus rot in peach.


Assuntos
Aminobutiratos/farmacologia , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Núcleo Celular/efeitos dos fármacos , Frutas/efeitos dos fármacos , Doenças das Plantas/prevenção & controle , Prunus persica/efeitos dos fármacos , Rhizopus/efeitos dos fármacos , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/genética , Núcleo Celular/genética , Núcleo Celular/metabolismo , Citoplasma/efeitos dos fármacos , Citoplasma/metabolismo , Resistência à Doença/efeitos dos fármacos , Resistência à Doença/genética , Frutas/microbiologia , Glutationa/metabolismo , NADP/metabolismo , Oxirredução , Via de Pentose Fosfato , Filogenia , Doenças das Plantas/microbiologia , Prunus persica/metabolismo , Prunus persica/microbiologia , Rhizopus/crescimento & desenvolvimento
10.
Int J Biol Macromol ; 159: 995-1003, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32439442

RESUMO

Iturin A is a natural antifungal agent that is widely used in the agriculture and food industries. In the present study, a new modified chitosan sub-micron, succinaldehydic acid (SAC) - chitosan (CS) system was synthesised by microwave irradiation and then as a carrier for capsulation of Iturin A (SAC-CS-IA). The structures of SAC-CS and SAC-CS-IA were characterised by SEM, NMR and FTIR. The size distribution suggested that the average size of SAC-CS and SAC-CS-IA was from 1.5 to 2.5 µm. An encapsulation efficiency of 92.02% under an adaptive pH (pH = 5) and time (5.5 h) was used. The study of release kinetics shows that about 80% of Iturin A was released in 25 days. An antifungal activity assay indicated that SAC-CS-IA exhibited higher antifungal activity against Ceratocystis fimbriata and Rhizopus strolonifer with 75.05 ± 3.24% and 80.54 ± 2.65%, respectively. The results indicate that the SAC-CS can improve the stability of IA on heat and pH with a wide range and tolerance most of enzymes. Actual tuber storage suggested that SAC-CS-IA can significantly inhibit pathogen fungal infection and reduce toxin product. Meanwhile, SAC-CS-IA could retain the water, starch, and soluble sugar contents. Low residue assay indicated that SAC-CS-IA could be used as an antifungal and anti-rotting agent in agriculture and food applications.


Assuntos
Antifúngicos/administração & dosagem , Cápsulas/química , Ceratocystis/efeitos dos fármacos , Quitosana/análogos & derivados , Peptídeos Cíclicos/administração & dosagem , Rhizopus/efeitos dos fármacos , Aldeídos/química , Antifúngicos/farmacologia , Liberação Controlada de Fármacos , Peptídeos Cíclicos/farmacologia
12.
Food Chem ; 321: 126701, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32283502

RESUMO

The antifungal activity of a library of twenty-four aromatic methoximes was examined against five representative postharvest phytopathogenic fungi. The panel included Penicillium digitatum, Penicillium italicum, Rhizopus stolonifer, Botrytis cinerea and Monilinia fructicola, all of which cause relevant economic losses worldwide as a result of affecting harvested fruits. The minimum inhibitory concentrations and minimum fungicidal concentrations of each compound were defined and the main structure-activity relationships were determined. Although other congeners were more potent, drug likeliness considerations pointed to the methoxime derived from 2,4-dihydroxypropiophenone as the compound with the most suitable profile. The morphology of the colonies of the fungal strains treated with the methoxime was examined microscopically and the compound was also tested in freshly harvested peaches and oranges, exhibiting promising control profiles in both fruits, similar to those of the commercial agents Imazalil and Carbendazim.


Assuntos
Antifúngicos/química , Antifúngicos/farmacologia , Frutas/microbiologia , Oximas/química , Ascomicetos/efeitos dos fármacos , Botrytis/efeitos dos fármacos , Citrus sinensis/efeitos dos fármacos , Citrus sinensis/microbiologia , Frutas/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Oximas/farmacologia , Penicillium/efeitos dos fármacos , Prunus persica/efeitos dos fármacos , Prunus persica/microbiologia , Rhizopus/efeitos dos fármacos , Relação Estrutura-Atividade
13.
Pediatr Infect Dis J ; 39(4): 310-312, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32084112

RESUMO

Posaconazole is a triazole antifungal with activity against Rhizopus, but data on its use and pharmacokinetics in preterm infants are scarce. In this case, a 24 4/7-week neonate's Rhizopus infection is successfully treated with debridement and combination antifungal therapy with amphotericin B, micafungin and enteral posaconazole. This is the first reported posaconazole use in a preterm neonate with Rhizopus.


Assuntos
Antifúngicos/uso terapêutico , Mucormicose/tratamento farmacológico , Triazóis/uso terapêutico , Anfotericina B/uso terapêutico , Quimioterapia Combinada , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Micafungina/uso terapêutico , Testes de Sensibilidade Microbiana , Mucormicose/diagnóstico , Rhizopus/efeitos dos fármacos
14.
Med Chem ; 16(1): 128-139, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30501601

RESUMO

BACKGROUND: It is assumed that the unfavorable selective toxicity of an antifungal drug Amphotericin B (AmB) can be improved upon chemical modification of the antibiotic molecule. OBJECTIVE: The aim of this study was verification of the hypothesis that introduction of bulky substituents at the amino sugar moiety of the antibiotic may result in diminishment of mammalian in vitro toxicity of thus prepared AmB derivatives. METHODS: Twenty-eight derivatives of AmB were obtained upon chemical modification of the amino group of mycosamine residue. This set comprised 10 N-succinimidyl-, 4 N-benzyl-, 5 Nthioureidyl- and 9 N-aminoacyl derivatives. Parameters characterizing biological in vitro activity of novel compounds were determined. RESULTS: All the novel compounds demonstrated lower than AmB antifungal in vitro activity but most of them exhibited negligible cytotoxicity against human erythrocytes and three mammalian cell lines. In consequence, the selective toxicity of majority of novel antifungals, reflected by the selective toxicity index (STI = EH50/IC50) was improved in comparison with that of AmB, especially in the case of 5 compounds. The novel AmB derivatives with the highest STI, induced substantial potassium efflux from Candida albicans cells at concentrations slightly lower than IC50s but did not trigger potassium release from human erythrocytes at concentrations lower than 100 µg/mL. CONCLUSION: Some of the novel AmB derivatives can be considered promising antifungal drug candidates.


Assuntos
Anfotericina B/farmacologia , Antifúngicos/farmacologia , Hexosaminas/farmacologia , Anfotericina B/síntese química , Anfotericina B/química , Antifúngicos/síntese química , Antifúngicos/química , Aspergillus/efeitos dos fármacos , Candida/efeitos dos fármacos , Cryptococcus/efeitos dos fármacos , Relação Dose-Resposta a Droga , Fusarium/efeitos dos fármacos , Hexosaminas/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Mucor/efeitos dos fármacos , Rhizopus/efeitos dos fármacos , Relação Estrutura-Atividade
15.
Pak J Pharm Sci ; 32(4(Supplementary)): 1849-1854, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31680082

RESUMO

The present study describes the antifungal potency of Nigella sativa seeds extract and the effect of immunomodulatory of N. sativa against aflatoxin- fed mice. Disc diffusion method was used for antifungal efficacy of aqueous extract of N. sativa. In animal experiments, lymphoid cell count, total and differential counts of PEC, the phagocytic activity of PEC and detection of the plaque-forming were determined. E-rosette-forming cells (RFC), T-cell mitogenesis assay cells, ALT and AST were detected. The aqueous extract of N. sativa (50%) exhibited high inhibition zone with most of isolates of R. stolonifera.The results indicated that treatment of mice by using N. sativa showed marked rise in the number of cells from thymus and PLN with dose 0.50 g and absolute number and comparative ratio of macrophages (P < 0.01) with the doses 0.40 and 0.50 g. There is gradually rise in the scavenger activity of PEC with the dose 0.50 g at 60 min. Serum level of ALT was markedly reduced with dose 0.50 g as compared with a control group. These results indicated that N. sativa is promising modifier of biological response.


Assuntos
Aflatoxinas/efeitos adversos , Antifúngicos/farmacologia , Nigella sativa/química , Extratos Vegetais/farmacologia , Rhizopus/efeitos dos fármacos , Sementes/química , Animais , Macrófagos/efeitos dos fármacos , Masculino , Camundongos
16.
ACS Infect Dis ; 5(11): 1887-1895, 2019 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-31535547

RESUMO

Rhizopus arrhizus (R. arrhizus) is a common causative agent of mucormycosis that usually enters the human body through the respiratory tract and skin. Both these sites harbor staphylococci as a part of the normal microflora, indicating the possibility of interspecies interactions. We aimed to elucidate this interaction and identify the molecular mechanisms involved. Both Staphylococcus aureus (S. aureus) and Staphylococcus epidermidis (S. epidermidis) substantially hindered R. arrhizus radial growth, spore germination, and liquid culture biomass. Secreted components in the stationary-phase supernatant were responsible for this activity. The active components, based on molecular weight-based fractionation, mass spectrometry, and ion exclusion chromatography, were identified as a truncated version of phenol soluble modulin α2 (Δ1Δ2PSMα2) and PSMα3 in S. aureus, PSMδ in S. epidermidis, and organic acids in both the species. Exposure to the phenol soluble modulins (PSMs) extensively damaged the fungal spores and pre-existing hyphae, leading to bleb formation, shriveling, hyphal shrinkage, and cell distortion.


Assuntos
Ácidos/farmacologia , Antifúngicos/farmacologia , Fenóis/farmacologia , Rhizopus/efeitos dos fármacos , Staphylococcus aureus/química , Staphylococcus epidermidis/química , Ácidos/química , Ácidos/metabolismo , Antibiose , Antifúngicos/química , Antifúngicos/metabolismo , Fenóis/química , Fenóis/metabolismo , Rhizopus/crescimento & desenvolvimento , Staphylococcus aureus/metabolismo , Staphylococcus epidermidis/metabolismo
17.
Artigo em Inglês | MEDLINE | ID: mdl-31374994

RESUMO

Tomatoes are among the most important horticultural crops; however, it is estimated that 30% of tomato yield is lost due to postharvest rot due to Rhizopus stolonifer, a fungus which requires lesions to initiate the infectious process. Tomato fruit cracking is a physiopathy which causes significant economic losses, since cracking is the door used by the fungus. In this experiment, 14 cultivars of tomato of different types were used. Fruit sampling was carried out in the middle of the crop cycle, coinciding with the peak of yield; then, the fruits were divided into two groups: one group was inoculated with Rhizopus in order to assess the effectiveness of washing, whilst the other was treated with sterile water. The fruits of each group were divided into lots to be treated with six washing treatments: dipping in hot water at 20, 40 and 60 °C for 20 s; the fruits were then sprayed with the following solutions: 0.6% of Hydrogen Peroxide 23% + Peracetic acid 15%; commercial bleach at 0.5% and 2% of Hydrogen Peroxide 50%. The control sample was not washed. The results show that there was an influence of cultivar on fruit cracking, which was strongly related with Rhizopus infection. Three cultivars were not susceptible to cracking, and therefore, were not sensitive to Rhizopus infection. The effectiveness of different washing treatments of tomato fruits depends on several factors; nonetheless, hot water treatment has been shown to be more effective than the use of chemical products such as commercial bleach or hydrogen peroxide. Another factor, the susceptibility of cultivars to cracking, determines the effectiveness of the washing treatment. The results provide an important basis for making decisions about the washing management of tomato fruits in packaging houses.


Assuntos
Produtos Agrícolas/microbiologia , Fungicidas Industriais/farmacologia , Rhizopus/patogenicidade , Solanum lycopersicum/microbiologia , Produtos Agrícolas/efeitos dos fármacos , Rhizopus/efeitos dos fármacos
18.
Infect Dis (Lond) ; 51(10): 730-737, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31364897

RESUMO

Background: Mucormycosis is a rare, worldwide fungal infection with high mortality, which mostly affects immunocompromised patients. Compared to large parts of Asia, Europe, and the USA, information on clinical expression and fungal species distribution in mucormycosis in Turkey is limited. Objectives and methods: The main aim of this study was to evaluate the demographic features of mucormycosis cases, identify the isolates at the species level by using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF), compare culture results with histopathological examination and determine the antifungal susceptibility patterns of the pathogens. Results: Between 2016 and 2018, 10 mucormycosis cases (six female, four male; age range: 35-74 years) were evaluated retrospectively. The predominance of the cases were in late autumn and winter. Diabetes mellitus was the most common underlying condition. Seven patients had rhinoorbitocerebral, two had pulmonary and one had cutaneous mucormycosis. By mycological culture and direct microscopic examination nine strains were identified as Rhizopus spp. and one as Mucor spp. Seven of these strains were identified at the species level by MALDI-TOF. Histopathological examination of eight tissues were reported as compatible with mucormycosis. All isolates were resistant to azoles and echinocandins. Two isolates were resistant to Amphotericin B and one was resistant to posaconazole. Surgical debridement combined with antifungal therapy was the main treatment option. The mortality rate was 40% (n = 4) and the mean number of days between the onset of complaints and the initiation of treatment was 9.25. Conclusions: Early, rapid and accurate diagnosis of mucormycosis is of critical importance in the treatment of immunosuppressed patients.


Assuntos
Mucormicose/diagnóstico , Adulto , Idoso , Antifúngicos/uso terapêutico , Feminino , Humanos , Laboratórios Hospitalares , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mucor/efeitos dos fármacos , Mucor/genética , Mucor/crescimento & desenvolvimento , Mucor/isolamento & purificação , Mucormicose/tratamento farmacológico , Mucormicose/microbiologia , Mucormicose/mortalidade , Estudos Retrospectivos , Rhizopus/efeitos dos fármacos , Rhizopus/genética , Rhizopus/crescimento & desenvolvimento , Rhizopus/isolamento & purificação , Estações do Ano , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Turquia
19.
Appl Environ Microbiol ; 85(21)2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31444208

RESUMO

DDT (dichlorodiphenyltrichloroethane) was used worldwide as an organochlorine insecticide to control agricultural pests and vectors of several insect-borne human diseases. It was banned in most industrialized countries; however, due to its persistence in the environment, DDT residues remain in environmental compartments, becoming long-term sources of exposure. To identify and select fungal species suitable for bioremediation of DDT-contaminated sites, soil samples were collected from DDT-contaminated agricultural soils in Poland, and 38 fungal taxa among 18 genera were isolated. Two of them, Trichoderma hamatum FBL 587 and Rhizopus arrhizus FBL 578, were tested for tolerance in the presence of 1-mg liter-1 DDT concentration by using two indices based on fungal growth rate and biomass production (the tolerance indices Rt:Rc and TI), showing a clear tolerance to DDT. The two selected strains were studied to evaluate catabolic versatility on 95 carbon sources with or without DDT by using the Phenotype MicroArray system and to investigate the induced oxidative stress responses. The two strains were able to use most of the substrates provided, resulting in both high metabolic versatility and ecological functionality in the use of carbon sources, despite the presence of DDT. The activation of specific metabolic responses with species-dependent antioxidant enzymes to cope with the induced chemical stress has been hypothesized, since the presence of DDT promoted a higher formation of reactive oxygen species in fungal cells than the controls. The tested fungi represent attractive potential candidates for bioremediation of DDT-contaminated soil and are worthy of further investigations.IMPORTANCE The spread and environmental accumulation of DDT over the years represent not only a threat to human health and ecological security but also a major challenge because of the complex chemical processes and technologies required for remediation. Saprotrophic fungi, isolated from contaminated sites, hold promise for their bioremediation potential toward toxic organic compounds, since they might provide an environment-friendly solution to contamination. Once we verified the high tolerance of autochthonous fungal strains to high concentrations of DDT, we showed how fungi from different phyla demonstrate a high metabolic versatility in the presence of DDT. The isolates showed the singular ability to keep their functionality, despite the DDT-induced production of reactive oxygen species.


Assuntos
Agricultura , DDT/metabolismo , Rhizopus/metabolismo , Microbiologia do Solo , Poluentes do Solo/metabolismo , Trichoderma/metabolismo , Biodegradação Ambiental , DDT/toxicidade , Tolerância a Medicamentos , Hidrocarbonetos Clorados/metabolismo , Inseticidas/metabolismo , Metaboloma , Estresse Oxidativo , Polônia , Espécies Reativas de Oxigênio/metabolismo , Rhizopus/efeitos dos fármacos , Rhizopus/crescimento & desenvolvimento , Rhizopus/isolamento & purificação , Solo/química , Trichoderma/efeitos dos fármacos , Trichoderma/crescimento & desenvolvimento , Trichoderma/isolamento & purificação
20.
Appl Microbiol Biotechnol ; 103(18): 7663-7674, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31297555

RESUMO

The inhibitory effect of Bacillomycin D, a cyclic lipopeptide, on Rhizopus stolonifer colonization of cherry tomato was studied, and its possible mechanism of action was explored. Bacillomycin D showed a direct inhibitory effect on R. stolonifer spore germination and mycelial growth in vitro. It conferred both a direct inhibitory effect on R. stolonifer growth in cherry tomato in vivo and induced host resistance in cherry tomato. Moreover, Bacillomycin D treatment significantly increased the activities of plant defense-related enzymes, including chitinase (CHI), ß-1,3-glucanase (GLU), phenylalanine ammonia-lyase (PAL), and peroxidase (POD). Real-time PCR (RT-PCR) showed that defense-related genes involved in the salicylic acid defense signaling pathway and genes encoding pathogenesis-related proteins were up-regulated in Bacillomycin D treatment. Furthermore, Bacillomycin D-C16 resulted in direct inhibition and a remarkable induced resistance to R. stolonifer which was higher than as induced by Bacillomycin D-C14. Together, the data indicated that Bacillomycin D can control the growth of R. stolonifer through both the direct inhibition of the fungus and the activation of defense-related genes and enzymes in cherry tomato.


Assuntos
Peptídeos Catiônicos Antimicrobianos/farmacologia , Frutas/microbiologia , Rhizopus/efeitos dos fármacos , Rhizopus/crescimento & desenvolvimento , Solanum lycopersicum/microbiologia , Quitinases/metabolismo , Frutas/enzimologia , Glucana 1,3-beta-Glucosidase/metabolismo , Solanum lycopersicum/enzimologia , Peroxidase/metabolismo , Fenilalanina Amônia-Liase/metabolismo , Doenças das Plantas/microbiologia , Esporos Fúngicos/efeitos dos fármacos , Esporos Fúngicos/crescimento & desenvolvimento
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