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1.
Int J Food Microbiol ; 425: 110886, 2024 Dec 02.
Artículo en Inglés | MEDLINE | ID: mdl-39214027

RESUMEN

The control of heat-resistant fungi (HRFs), which cause spoilage of heat-treated fruit products, is considered a challenge for the fruit juice and beverage industry and requires new strategies for the development of antifungal compounds. In this study, four antifungal proteins (AFPs) from Penicillium digitatum (PdAfpB) and Penicillium expansum (PeAfpA, PeAfpB and PeAfpC), were evaluated against conidia from a representative collection of HRFs. A total of 19 strains from 16 different species belonging to the genera Aspergillus, Hamigera, Paecilomyces, Rasamsonia, Sarocladium, Talaromyces and Thermoascus were included in the study. PeAfpA and PdAfpB exhibited potent antifungal activity in synthetic media, completely inhibiting the growth of most of the fungi evaluated in the range of 0.5-32 µg/mL. The efficacy of the four AFPs was also tested in fruit juices against ascospores of five HRFs relevant to the food industry, including P. fulvus, P. niveus, P. variotii, A. fischeri and T. flavus. PdAfpB was the most effective protein in fruit juices, since it completely inhibited the growth of the five species tested in at least one of the fruit juices evaluated. This is the first study to demonstrate the activity of AFPs against fungal ascospores. Finally, a challenge test study showed that PdAfpB, at a concentration of 32 µg/mL, protected apple fruit juice artificially inoculated with ascospores of P. variotii for 17 days, highlighting the potential of the protein as a preservative in the fruit juice industry.


Asunto(s)
Antifúngicos , Conservación de Alimentos , Jugos de Frutas y Vegetales , Proteínas Fúngicas , Penicillium , Jugos de Frutas y Vegetales/microbiología , Penicillium/efectos de los fármacos , Penicillium/crecimiento & desarrollo , Conservación de Alimentos/métodos , Antifúngicos/farmacología , Proteínas Fúngicas/farmacología , Calor , Hongos/efectos de los fármacos , Hongos/crecimiento & desarrollo , Esporas Fúngicas/efectos de los fármacos , Esporas Fúngicas/crecimiento & desarrollo , Viabilidad Microbiana/efectos de los fármacos , Microbiología de Alimentos
2.
Open Forum Infect Dis ; 11(7): ofae323, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38966852

RESUMEN

We present the first case of native aortic valve endocarditis caused by Scopulariopsis. Intraoperative images and videos from valve replacement surgery illustrate the severity of fungal endocarditis. This case demonstrates the aggressive presentation of left-sided fungal endocarditis, highlights challenges with treating highly resistant fungi, and considers the potential utility of olorofim.

3.
Environ Sci Nano ; 11(2): 637-644, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38841652

RESUMEN

Infections caused by fungi are emerging global health challenges that are exacerbated by the formation of fungal biofilms. Further challenges arise from environmental contamination with antifungal agents, which promotes environmental acquisition of antifungal resistance. We report the generation of an efficient, sustainable, all-natural antifungal nanotherapeutic based on the integration of an antimicrobial natural essential oil into a gelatin-based nanoemulsion platform. Carvacrol-loaded gelatin nanoemulsions penetrated Candida albicans biofilms, resulting in death of C. albicans cells in biofilms, and displayed selective biofilm elimination without harmful effects on fibroblast cells in a fungal biofilm-mammalian fibroblast co-culture model. Furthermore, the nanoemulsions degraded in the presence of physiologically relevant biomolecules, reducing the potential for environmental pollution and ecotoxicity. Overall, the sustainability, and efficacy of the described gelatin nanoemulsion formulation provides an environmentally friendly strategy for treating biofilm-associated fungal infections, including those caused by drug-resistant fungi.

4.
Microb Cell Fact ; 23(1): 161, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38822407

RESUMEN

Multi resistant fungi are on the rise, and our arsenal compounds are limited to few choices in the market such as polyenes, pyrimidine analogs, azoles, allylamines, and echinocandins. Although each of these drugs featured a unique mechanism, antifungal resistant strains did emerge and continued to arise against them worldwide. Moreover, the genetic variation between fungi and their host humans is small, which leads to significant challenges in new antifungal drug discovery. Endophytes are still an underexplored source of bioactive secondary metabolites. Many studies were conducted to isolate and screen endophytic pure compounds with efficacy against resistant yeasts and fungi; especially, Candida albicans, C. auris, Cryptococcus neoformans and Aspergillus fumigatus, which encouraged writing this review to critically analyze the chemical nature, potency, and fungal source of the isolated endophytic compounds as well as their novelty features and SAR when possible. Herein, we report a comprehensive list of around 320 assayed antifungal compounds against Candida albicans, C. auris, Cryptococcus neoformans and Aspergillus fumigatus in the period 1980-2024, the majority of which were isolated from fungi of orders Eurotiales and Hypocreales associated with terrestrial plants, probably due to the ease of laboratory cultivation of these strains. 46% of the reviewed compounds were active against C. albicans, 23% against C. neoformans, 29% against A. fumigatus and only 2% against C. auris. Coculturing was proved to be an effective technique to induce cryptic metabolites absent in other axenic cultures or host extract cultures, with Irperide as the most promising compounds MIC value 1 µg/mL. C. auris was susceptible to only persephacin and rubiginosin C. The latter showed potent inhibition against this recalcitrant strain in a non-fungicide way, which unveils the potential of fungal biofilm inhibition. Further development of culturing techniques and activation of silent metabolic pathways would be favorable to inspire the search for novel bioactive antifungals.


Asunto(s)
Antifúngicos , Endófitos , Antifúngicos/farmacología , Endófitos/metabolismo , Humanos , Pruebas de Sensibilidad Microbiana , Cryptococcus neoformans/efectos de los fármacos , Cryptococcus neoformans/metabolismo , Hongos/efectos de los fármacos , Hongos/metabolismo , Aspergillus fumigatus/efectos de los fármacos , Aspergillus fumigatus/metabolismo , Candida albicans/efectos de los fármacos
5.
Food Chem ; 453: 139583, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-38772305

RESUMEN

Food preservatives are crucial in fruit production, but fungal resistance is a challenge. The main objective was to compare the sensitivity of Neosartorya spp. isolates to preservatives used in food security applications and to assess the role of metabolic properties in shaping Neosartorya spp. resistance. Sodium metabisulfite, potassium sorbate, sodium bisulfite and sorbic acid showed inhibitory effects, with sodium metabisulfite the most effective. Tested metabolic profiles included fungal growth intensity and utilization of amines and amides, amino acids, polymers, carbohydrates and carboxylic acids. Significant decreases in the utilization of all tested organic compound guilds were observed after fungal exposure to food preservatives compared to the control. Although the current investigation was limited in the number of predominately carbohydrate substrates and the breadth of metabolic responses, extensive sensitivity panels are logical step in establishing a course of action against spoilage agents in food production being important approach for innovative food chemistry.


Asunto(s)
Contaminación de Alimentos , Conservantes de Alimentos , Conservantes de Alimentos/farmacología , Conservantes de Alimentos/química , Contaminación de Alimentos/análisis , Neosartorya/metabolismo , Neosartorya/química , Neosartorya/crecimiento & desarrollo , Metaboloma
6.
Mycopathologia ; 189(2): 30, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38578519

RESUMEN

OBJECTIVE: To study the distribution of pathogenic Aspergillus strains of otomycosis in central China and the identification of their antifungal sensitivity. METHODS: We collected external ear canal secretions clinically diagnosed as otomycosis from April 2020 to January 2023 from the Department of Otolaryngology-Head and Neck Surgery in central China. The pathogenic Aspergillus strains were identified through morphological examination and sequencing. The antifungal sensitivity was performed using the broth microdilution method described in the Clinical Laboratory Standard Institute document M38-A3. RESULTS: In the 452 clinical strains isolated from the external ear canal, 284 were identified as Aspergillus terreus (62.83%), 92 as Aspergillus flavus (20.35%), 55 as Aspergillus niger (12.17%). In antifungal susceptibility tests the MIC of Aspergillus strains to bifonazole and clotrimazole was high,all the MIC90 is > 16 ug/mL. However, most Aspergillus isolates show moderate greatly against terbinafine, itraconazole and voriconazole. CONCLUSION: A. terreus is the most common pathogenic Aspergillus strain in otomycosis in central China. The selected topical antifungal drugs were bifonazole and clotrimazole; the drug resistance rate was approximately 30%. If the infection is persistent and requires systemic treatment, terbinafine and itraconazole can be used. The resistance of Aspergillus in otomycosis to voriconazole should be screened to avoid the systemic spread of infection in immunocompromised people and poor compliance with treatment. However, the pan-azole-resistant strain of Aspergillus should be monitored, particularly in high-risk patients with otomycosis.


Asunto(s)
Aspergilosis , Otomicosis , Humanos , Antifúngicos/farmacología , Otomicosis/epidemiología , Otomicosis/microbiología , Itraconazol , Voriconazol , Terbinafina , Clotrimazol/farmacología , Aspergilosis/epidemiología , Aspergilosis/microbiología , Aspergillus , Pruebas de Sensibilidad Microbiana
7.
J Fungi (Basel) ; 9(12)2023 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-38132730

RESUMEN

During the course of a project investigating culturable Ascomycota diversity from freshwater sediments in Spain, we isolated 63 strains of cycloheximide-resistant fungi belonging to the order Onygenales. These well-known ascomycetes, able to infect both humans and animals, are commonly found in terrestrial habitats, colonizing keratin-rich soils or dung. Little is known about their diversity in aquatic environments. Combining morphological features and sequence analyses of the ITS and LSU regions of the nrDNA, we identified 14 species distributed in the genera Aphanoascus, Arachniotus, Arthroderma, Arthropsis, Emmonsiellopsis, Gymnoascoideus, Leucothecium, Malbranchea, and Myriodontium. Furthermore, three novel species for the genus Malbranchea are proposed as M. echinulata sp. nov., M. irregularis sp. nov., and M. sinuata sp. nov. The new genera Albidomyces and Neoarthropsis are introduced based on Arachniotus albicans and Arthropsis hispanica, respectively. Neoarthropsis sexualis sp. nov. is characterized and differentiated morphologically from its counterpart by the production of a sexual morph. The novel family Neoarthropsidaceae is proposed for the genera Albidomyes, Apinisia, Arachnotheca, Myriodontium, and Neoarthropsis, based on their phylogenetic relationships and phenotypic and ecological traits. Pseudoamaurascopsis gen. nov. is introduced to accommodate P. spiralis sp. nov., a fungus with unclear taxonomy related to Amaurascopsis and Polytolypa. We traced the ecology and global distribution of the novel fungi through ITS environmental sequences deposited in the GlobalFungi database. Studying the fungal diversity from freshwater sediments not only contributes to filling gaps in the relationships and taxonomy of the Ascomycota but also gives us insights into the fungal community that might represent a putative risk to the health of animals and humans inhabiting or transient in aquatic environments.

8.
Eur J Med Chem ; 260: 115777, 2023 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-37660485

RESUMEN

A series of spiro[pyrrolidine-2,3'-quinoline]-2'-one derivatives were designed and synthesized for the discovery of novel antifungal drugs. The bioactivities of all derivatives were screened by evaluating their inhibitory effects against chitin synthase (CHS) and antimicrobial activities in vitro. Enzyme inhibition experiments showed that all the synthesized compounds inhibited the chitin synthase. Compounds 4d, 4k, 4n and 4o showed inhibitory effects against CHS with IC50 values which were close to that of the control drug (polyoxin B). The results of enzyme kinetics experiment showed that these compounds were non-competitive inhibitors of chitin synthase (Ki of compound 4o is 0.14 mM). Antimicrobial experiments showed that these compounds exhibited moderate to excellent antifungal activity against pathogenic fungal strains while the compounds showed little potency against bacteria. Among them, compounds 4d, 4f, 4k and 4n showed stronger antifungal activities against C. albicans than those of fluconazole and polyoxin B. Compounds 4f, 4n and 4o showed better antifungal activities against A. flavus than those of fluconazole and polyoxin B. Compound 4d showed similar activity to that of fluconazole and stronger activity than those of polyoxin B against C. neoformans and A. fumigatus. It is also showed that these compounds have the potency against drug-resistant fungal variants. The results of sorbitol protection assay and evaluation of antifungal activity against micafungin-resistant strains experiment further illustrated that these compounds inhibited the synthesis of chitin of fungal cell wall. Drug combination experiments showed that these compounds had synergistic or additive effects when combined with fluconazole or polyoxin B. The synergistic effects with polyoxin B further confirmed the compounds were non-competitive inhibitors of chitin synthase. Additionally, docking studies showed that these compounds had strong affinity with chitin synthase from C. albicans (CaChs2). These results indicate that the target of these synthesized compounds is chitin synthase, and these compounds had excellent antifungal activity while possessed the potency against drug-resistant fungal variants.


Asunto(s)
Cryptococcus neoformans , Quinolinas , Antifúngicos/farmacología , Fluconazol , Quitina Sintasa , Quitina , Candida albicans , Piperazinas
9.
Eur J Med Chem ; 255: 115388, 2023 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-37141707

RESUMEN

A series of spiro-quinazolinone scaffolds were constructed based on the bioactivity of quinazolinone and the inherent feature of spirocycle to design novel chitin synthase inhibitors that possess mode of action different from that of the currently used antifungal agents. Among them, the spiro[thiophen-quinazolin]-one derivatives containing α, ß-unsaturated carbonyl fragments had shown inhibitory activities against chitin synthase and antifungal activities. The enzymatic experiments showed that among the sixteen compounds, compounds 12d, 12g, 12j, 12l and 12m exhibited inhibitions against chitin synthase with IC50 values of 116.7 ± 19.6 µM, 106.7 ± 14.2 µM, 102.3 ± 9.6 µM, 122.7 ± 22.2 µM and 136.8 ± 12.4 µM, respectively, which were comparable to that of polyoxin B (IC50 = 93.5 ± 11.1 µM). The assays of enzymatic Kinetic parameters showed that compound 12g was a non-competitive inhibitor of chitin synthase. The antifungal assays showed that compounds 12d, 12g, 12j, 12l and 12m exhibited a broad-spectrum of antifungal activity against the four strains tested in vitro. In which, compounds 12g and 12j had stronger antifungal activity against four tested strains than that of polyoxin B and similar to that of fluconazole, while compounds 12d, 12l and 12m showed antifungal activity comparable to that of polyoxin B against four tested strains. Meanwhile, compounds 12d, 12g, 12j, 12l and 12m exhibited good antifungal activity against fluconazole-resistant and micafungin-resistant fungi variants with MIC values ranging from 4 to 32 µg/mL while the MIC values of reference drugs were above 256 µg/mL. Furthermore, the results of drug-combination experiments showed that compounds 12d, 12g, 12j, 12l and 12m had synergistic or additive effects with fluconazole or polyoxin B. The results of sorbitol protection experiment and the experiment of antifungal activity against micafungin-resistant fungi further demonstrated that these compounds target chitin synthase. The result of cytotoxicity assay showed that compound 12g had low toxicity toward human lung cancer A549 cells and the ADME analysis in silico displayed that compound 12g possessed promising pharmacokinetic properties. The molecular docking indicated that compound 12g formed multiple hydrogen bond interactions binding to chitin synthase, which might be conductive to increasing the binding affinity and inhibiting the activity of chitin synthase. The above results indicated that the designed compounds were chitin synthase inhibitors with selectivity and broad-spectrum antifungal activity and could be act as the lead compounds against drug-resistant fungi.


Asunto(s)
Antifúngicos , Quitina Sintasa , Humanos , Antifúngicos/química , Relación Estructura-Actividad , Inhibidores Enzimáticos/química , Quinazolinonas/farmacología , Fluconazol , Micafungina , Quitina , Simulación del Acoplamiento Molecular , Pruebas de Sensibilidad Microbiana , Hongos/metabolismo , Diseño de Fármacos
10.
Eur J Med Chem ; 243: 114723, 2022 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-36070631

RESUMEN

Four series of spiro[benzoxazine-piperidin]-one derivatives were designed and synthesized. Their inhibition percentages against chitin synthase and antifungal activities were evaluated. Based on the preliminary biological assays, the series of derivatives containing α, ß-unsaturated carbonyl fragment which had moderate to excellent CHS inhibitory activity and antifungal activity were further researched. In this series of compounds, eight out of twenty-one compounds had good to excellent inhibitory activity against chitin synthase with an inhibition percentage value above 60% at the concentration of 300 µg/mL. Among them, compounds 9a, 9o, 9s and 9t showed excellent chitin synthase inhibitory activity with IC50 values of 0.14 mM, 0.11 mM, 0.10 mM and 0.16 mM, respectively, which were equal to that of the control drug (polyoxin B). The results of sorbitol protection assays and evaluation of antifungal activity against micafungin-resistant fungi further proved that the target of these synthesized compounds was chitin synthase. The antifungal activity evaluation showed that compounds 9a, 9d, 9h, 9s and 9t had broad-spectrum antifungal activity in vitro and their antifungal activities are equal to those of fluconazole and polyoxin B. The result of combination use showed this series of compounds combined with fluconazole had additive or synergistic effects. In addition, compounds 9a, 9o and 9t showed good antifungal activity against fluconazole-resistant C. albicans and fluconazole-resistant C. neoformans variants. Consequently, the results showed that these compounds were chitin synthase inhibitors and antifungal agents and had significant activity against drug-resistant fungal variants.


Asunto(s)
Antifúngicos , Quitina Sintasa , Antifúngicos/farmacología , Fluconazol/farmacología , Benzoxazinas/farmacología , Candida albicans , Quitina/farmacología , Pruebas de Sensibilidad Microbiana , Relación Estructura-Actividad , Inhibidores Enzimáticos/farmacología
11.
J Infect Public Health ; 15(9): 986-1000, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35981408

RESUMEN

With the widespread use of immunosuppressive agents and the increase in patients with severe infections, the incidence of fungal infections worldwide has increased year by year. The fungal pathogens Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus cause a total of more than 1 million deaths each year. Long-term use of antifungal drugs can easily lead to fungal resistance, and the prevalence of drug-resistant fungi is a major global health challenge. In order to effectively control global fungal infections, there is an urgent need for new drugs that can exert effective antifungal activity and overcome drug resistance. We must promote the discovery of new antifungal targets and drugs, and find effective ways to control drug-resistant fungi through different ways, so as to reduce the threat of drug-resistant fungi to human life, health and safety. In the past few years, certain progress has been made in the research and development of antifungal drugs. In addition to summarizing some of the antifungal drugs currently approved by the FDA, this review also focuses on potential antifungal drugs, the repositioned drugs, and drugs that can treat drug-resistant bacteria and fungal infections, and provide new ideas for the development of antifungal drugs in the future.


Asunto(s)
Cryptococcus neoformans , Micosis , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Aspergillus fumigatus , Humanos , Micosis/tratamiento farmacológico
12.
Saudi J Biol Sci ; 29(5): 3207-3212, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35844424

RESUMEN

The crude aqueous and ethanolic leaf extracts of Coccinia indica were screened for methicillin resistant Staphylococcus aureus (MRSA), multidrug resistant (MDR) Streptococcus pyogenes, Escherichia coli, Candida auris and Trichophyton rubrum. Antibacterial and antifungal activities were assessed by standard disc diffusion and tube dilution methods. The results showed that ethanolic extract inhibited MRSA, C. auris at 250 µg/mL and S. pyogenes at 200 µg/mL comparable to the susceptible antibiotics used as positive controls. There was no observable activity against T. rubrum, while a mild activity was observed with ethanolic extracts over E. coli at higher concentrations which did not turn out to be complete or significant inhibition. Aqueous extract did not exhibit any observable activity over the five organisms tested. Furthermore, the results showed clear cut concentration dependent antibacterial and antifungal activities with additional variation of specific activity over Gram positive and negative bacteria, yeast and filamentous fungi. So, it is evident that ethanolic extract of Coccinia indica could be further escalating for mechanistic studies in the era of multidrug resistance, indigenous preparations from herbs could be a safe choice over clinically challenging organisms.

13.
Rev Iberoam Micol ; 39(2): 44-49, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35753971

RESUMEN

BACKGROUND: The cryptic Aspegillus species are rare, these microorganisms are usually more resistant to common antifungal therapies. Therefore, a correct identification is important when evaluating the impact of such species in aspergillosis. AIMS: We aimed to describe the frequency, clinical and microbiological characteristics, and the outcomes of those cases of aspergillosis caused by cryptic species in a tertiary hospital. METHODS: We retrospectively identified all microbiologically documented cases of aspergillosis between January 2013 and December 2018. Definitive species identification of clinically significant isolates was achieved via sequencing methods. The polymerase chain reaction (PCR) products were sequenced, and the results obtained were compared to sequences deposited in GenBank. Antifungal susceptibility testing was performed using the Sensititre® YeastOne® panel. RESULTS: A total of 679 Aspergillus isolates were recovered from 489 patients, of which 109 were clinically relevant. Ten (9.2%) isolates were identified as cryptic species: Aspergillus arcoverdensis (2), Aspergillus lentulus (2), Aspergillus ellipticus (2), Aspergillus alliaceus (1), Aspergillus nomius (1), Aspergillus tubingensis (1) and Aspergillus montevidensis (1). Most patients already suffered some type of immunosuppression. Half of these patients had required intensive care before the infection showed up, and most of them had a pulmonary infection. Mortality at the 100-day follow-up was 40%. Antifungal susceptibility testing was performed on three of the isolates (A. arcoverdensis, A. tubingensis and A. nomius), which showed high minimum inhibitory concentrations (MIC) for azoles and amphotericin B. CONCLUSIONS: The frequency of cryptic species in our centre was 9.2%. Most patients had some degree of immunosuppression, and the mortality rate was 40%.


Asunto(s)
Antifúngicos , Aspergilosis , Anfotericina B/farmacología , Anfotericina B/uso terapéutico , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Aspergilosis/tratamiento farmacológico , Aspergilosis/epidemiología , Aspergilosis/microbiología , Aspergillus , Humanos , Pruebas de Sensibilidad Microbiana , Estudios Retrospectivos
14.
Rev. iberoam. micol ; 39(2): 44-49, abril 2022. tab
Artículo en Inglés | IBECS | ID: ibc-207101

RESUMEN

Background:The cryptic Aspegillus species are rare, these microorganisms are usually more resistant to common antifungal therapies. Therefore, a correct identification is important when evaluating the impact of such species in aspergillosis.Aims:We aimed to describe the frequency, clinical and microbiological characteristics, and the outcomes of those cases of aspergillosis caused by cryptic species in a tertiary hospital.Methods:We retrospectively identified all microbiologically documented cases of aspergillosis between January 2013 and December 2018. Definitive species identification of clinically significant isolates was achieved via sequencing methods. The polymerase chain reaction (PCR) products were sequenced, and the results obtained were compared to sequences deposited in GenBank. Antifungal susceptibility testing was performed using the Sensititre® YeastOne® panel.Results:A total of 679 Aspergillus isolates were recovered from 489 patients, of which 109 were clinically relevant. Ten (9.2%) isolates were identified as cryptic species: Aspergillus arcoverdensis (2), Aspergillus lentulus (2), Aspergillus ellipticus (2), Aspergillus alliaceus (1), Aspergillus nomius (1), Aspergillus tubingensis (1) and Aspergillus montevidensis (1). Most patients already suffered some type of immunosuppression. Half of these patients had required intensive care before the infection showed up, and most of them had a pulmonary infection. Mortality at the 100-day follow-up was 40%. Antifungal susceptibility testing was performed on three of the isolates (A. arcoverdensis, A. tubingensis and A. nomius), which showed high minimum inhibitory concentrations (MIC) for azoles and amphotericin B.Conclusions:The frequency of cryptic species in our centre was 9.2%. Most patients had some degree of immunosuppression, and the mortality rate was 40%. (AU)


Antecedentes:Las especies crípticas dentro del género Aspergillus son poco habituales, pero suelen mostrar una mayor resistencia al tratamiento antifúngico convencional. Por tanto, una correcta identificación de la especie es necesaria para evaluar el impacto de estas especies crípticas en el desarrollo de la aspergilosis.Objetivos:El objetivo de este estudio fue describir las características clínicas, epidemiológicas y microbiológicas, así como la evolución clínica, de los casos de aspergilosis por especies crípticas en un hospital de tercer nivel.Métodos:Se analizaron de forma retrospectiva todos los casos documentados de aspergilosis con identificación microbiológica entre enero de 2013 y diciembre de 2018. La identificación definitiva de los aislamientos clínicos se realizó mediante métodos de secuenciación. Los productos de amplificación obtenidos por la reacción en cadena de la polimerasa (PCR) fueron secuenciados, y los resultados se analizaron utilizando la base de datos del GenBank. Para el análisis de susceptibilidad a los antifúngicos de los aislamientos identificados se utilizó el panel Sensititre® YeastOne®.Resultados:Se identificaron un total de 679 aislamientos de Aspergillus de 489 pacientes, de los cuales un total de 109 eran clínicamente relevantes. Diez (9,2%) de los aislamientos correspondían a especies crípticas: Aspergillus arcoverdensis (2), Aspergillus lentulus (2), Aspergillus ellipticus (2), Aspergillus alliaceus (1), Aspergillus nomius (1), Aspergillus tubingensis (1) y Aspergillus montevidensis (1). La mayoría de los pacientes tenían algún tipo de inmunosupresión previa. La mitad de estos pacientes habían requerido de cuidados intensivos antes de la infección, y la mayoría sufría una infección pulmonar. La mortalidad a los 100 días de seguimiento fue del 40%. (AU)


Asunto(s)
Humanos , Anfotericina B/farmacología , Anfotericina B/uso terapéutico , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Aspergilosis/tratamiento farmacológico , Aspergilosis/epidemiología , Aspergilosis/microbiología , Pruebas de Sensibilidad Microbiana , Estudios Retrospectivos
15.
Angew Chem Int Ed Engl ; 61(17): e202200778, 2022 04 19.
Artículo en Inglés | MEDLINE | ID: mdl-35182092

RESUMEN

New antifungals are urgently needed to combat invasive fungal infections, due to limited types of available antifungal drugs and frequently encountered side effects, as well as the quick emergence of drug-resistance. We previously developed amine-pendent poly(2-oxazoline)s (POXs) as synthetic mimics of host defense peptides (HDPs) to have antibacterial properties, but with poor antifungal activity. Hereby, we report the finding of short guanidinium-pendent POXs, inspired by cell-penetrating peptides, as synthetic mimics of HDPs to display potent antifungal activity, superior mammalian cells versus fungi selectivity, and strong therapeutic efficacy in treating local and systemic fungal infections. Moreover, the unique antifungal mechanism of fungal cell membrane penetration and organelle disruption explains the insusceptibility of POXs to antifungal resistance. The easy synthesis and structural diversity of POXs imply their potential as a class of promising antifungal agents.


Asunto(s)
Antiinfecciosos , Micosis , Animales , Antiinfecciosos/farmacología , Antifúngicos/química , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Péptidos Catiónicos Antimicrobianos/farmacología , Hongos , Guanidina/farmacología , Mamíferos , Pruebas de Sensibilidad Microbiana , Micosis/tratamiento farmacológico , Oxazoles
16.
Eur J Med Chem ; 233: 114208, 2022 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-35220015

RESUMEN

A series of novel spiro-quinolinone derivatives were designed and synthesized and their structures were confirmed by spectroscopic methods. The enzymatic experiments showed that all the seventeen synthesized compounds had inhibition potency against chitin synthase, among them five compounds had excellent inhibition potency that equal to that of polyoxin B. The Kinetic parameters of enzymatic assays indicated that these compounds were non-competitive inhibitors of chitin synthase. The antimicrobial experiments displayed that the synthesized compounds had selectively and broad-spectrum antifungal activity in vitro Among them, two compounds had stronger antifungal activity against C. albicans than that of fluconazole meanwhile five others compounds showed antifungal activity against C. albicans being equal to that of fluconazole. Moreover, there are four or five compounds that possessed antifungal activities against C. neoformans, A. fumigatus and A. flavus as high as fluconazole had, respectively. The sorbitol protection assay and evaluation of antifungal activity against micafungin-resistant strain further verified that these compounds possessed antifungal activity through inhibiting the synthesis of chitin of cell wall. The evaluation of antifungal activity against others drug-resistant fungi variants showed these designed compounds had significant antifungal activity against these tested variants. The combination use experiments exhibited that the synthesized compounds had synergistic effects or additive effects with current used drugs in clinic. These results demonstrated that these synthesized compounds were chitin synthase inhibitors and had selective and broad-spectra antifungal activities.


Asunto(s)
Antifúngicos , Quitina Sintasa , Antifúngicos/química , Candida albicans , Quitina/farmacología , Diseño de Fármacos , Inhibidores Enzimáticos/química , Pruebas de Sensibilidad Microbiana , Pirrolidinas/farmacología , Relación Estructura-Actividad
17.
Int J Mol Sci ; 22(13)2021 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-34201733

RESUMEN

The emergence of fungal "superbugs" resistant to the limited cohort of anti-fungal agents available to clinicians is eroding our ability to effectively treat infections by these virulent pathogens. As the threat of fungal infection is escalating worldwide, this dwindling response capacity is fueling concerns of impending global health emergencies. These developments underscore the urgent need for new classes of anti-fungal drugs and, therefore, the identification of new targets. Phosphoinositide signaling does not immediately appear to offer attractive targets due to its evolutionary conservation across the Eukaryota. However, recent evidence argues otherwise. Herein, we discuss the evidence identifying Sec14-like phosphatidylinositol transfer proteins (PITPs) as unexplored portals through which phosphoinositide signaling in virulent fungi can be chemically disrupted with exquisite selectivity. Recent identification of lead compounds that target fungal Sec14 proteins, derived from several distinct chemical scaffolds, reveals exciting inroads into the rational design of next generation Sec14 inhibitors. Development of appropriately refined next generation Sec14-directed inhibitors promises to expand the chemical weaponry available for deployment in the shifting field of engagement between fungal pathogens and their human hosts.


Asunto(s)
Antifúngicos/farmacología , Micosis/tratamiento farmacológico , Proteínas de Transferencia de Fosfolípidos/antagonistas & inhibidores , Animales , Humanos , Micosis/metabolismo
18.
J Fungi (Basel) ; 7(3)2021 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-33802751

RESUMEN

Ascospores of Talaromyces.macrosporus belong to the most stress resistant eukaryotic cells and show a constitutive dormancy, i.e., no germination occurs in the presence of rich growth medium. Only an extreme trigger as very high temperature or pressure is able to evoke synchronized germination. In this study, several changes within the thick cell wall of these cells are observed after a heat treatment: (i.) a change in its structure as shown with EPR and X-ray diffraction; (ii.) a release of an abundant protein into the supernatant, which is proportional to the extent of heat activation; (iii.) a change in the permeability of the cell wall as judged by fluorescence studies in which staining of the interior of the cell wall correlates with germination of individual ascospores. The gene encoding the protein, dubbed ICARUS, was studied in detail and was expressed under growth conditions that showed intense ascomata (fruit body) and ascospore formation. It encodes a small 7-14 kD protein. Blast search exhibits that different Talaromyces species show a similar sequence, indicating that the protein also occurs in other species of the genus. Deletion strains show delayed ascomata formation, release of pigments into the growth medium, higher permeability of the cell wall and a markedly shorter heat activation needed for activation. Further, wild type ascospores are more heat-resistant. All these observations suggest that the protein plays a role in dormancy and is related to the structure and permeability of the ascospore cell wall. However, more research on this topic is needed to study constitutive dormancy in other fungal species that form stress-resistant ascospores.

19.
J Fungi (Basel) ; 7(3)2021 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-33809682

RESUMEN

Candida auris is a multidrug-resistant pathogen that represents a serious public health threat due to its rapid global emergence, increasing incidence of healthcare-associated outbreaks, and high rates of antifungal resistance. Whole-genome sequencing and genomic surveillance have the potential to bolster C. auris surveillance networks moving forward. Laboratories conducting genomic surveillance need to be able to compare analyses from various national and international surveillance partners to ensure that results are mutually trusted and understood. Therefore, we established an empirical outbreak benchmark dataset consisting of 23 C. auris genomes to help validate comparisons of genomic analyses and facilitate communication among surveillance networks. Our outbreak benchmark dataset represents a polyclonal phylogeny with three subclades. The genomes in this dataset are from well-vetted studies that are supported by multiple lines of evidence, which demonstrate that the whole-genome sequencing data, phylogenetic tree, and epidemiological data are all in agreement. This C. auris benchmark set allows for standardized comparisons of phylogenomic pipelines, ultimately promoting effective C. auris collaborations.

20.
Sci Total Environ ; 671: 676-684, 2019 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-30939320

RESUMEN

Reducing Hg contamination in soil using eco-friendly approaches has attracted increasing attention in recent years. In this study, a novel multi-metal-resistant Hg-volatilizing fungus belonging to Lecythophora sp., DC-F1, was isolated from multi-metal-polluted mining-area soil, and its performance in reducing Hg bioavailability in soil when used in combination with biochar was investigated. The isolate displayed a minimum inhibitory concentration of 84.5mg·L-1 for Hg(II) and volatilized >86% of Hg(II) from LB liquid medium with an initial concentration of 7.0mg·L-1 within 16h. Hg(II) contents in soils and grown lettuce shoots decreased by 13.3-26.1% and 49.5-67.7%, respectively, with DC-F1 and/or biochar addition compared with a control over 56days of incubation. Moreover, treatment with both bioagents achieved the lowest Hg content in lettuce shoots. Hg presence and DC-F1 addition significantly decreased the number of fungal ITS gene copies in soils. High-throughput sequencing showed that the soil fungal community compositions were more largely influenced by DC-F1 addition than by biochar addition, with the proportion of Mortierella increasing and those of Penicillium and Thielavia decreasing with DC-F1 addition. Developing the coupling of Lecythophora sp. DC-F1 with biochar into a feasible approach for the recovery of Hg-contaminated soils is promising.


Asunto(s)
Biodegradación Ambiental , Hongos/metabolismo , Mercurio/metabolismo , Microbiología del Suelo , Contaminantes del Suelo/metabolismo , Carbón Orgánico , Micobioma , Volatilización
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