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1.
Mar Drugs ; 22(6)2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38921585

RESUMO

Talaromyces, a filamentous fungus widely distributed across terrestrial and marine environments, can produce a diverse array of natural products, including alkaloids, polyketones, and polyketide-terpenoids. Among these, chrodrimanins represented a typical class of natural products. In this study, we isolated three previously undescribed pentaketide-sesquiterpenes, 8,9-epi-chrodrimanins (1-3), along with eight known compounds (4-11). The structures of compounds 1-3 were elucidated using nuclear magnetic resonance (NMR) and mass spectrometry (MS), while their absolute configurations were determined through X-ray crystallography and electronic circular dichroism (ECD) computations. The biosynthetic pathways of compounds 1-3 initiate with 6-hydroxymellein and involve multiple stages of isoprenylation, cyclization, oxidation, and acetylation. We selected four strains of gastrointestinal cancer cells for activity evaluation. We found that compound 3 selectively inhibited MKN-45, whereas compounds 1 and 2 exhibited no significant inhibitory activity against the four cell lines. These findings suggested that 8,9-epi-chrodrimanins could serve as scaffold compounds for further structural modifications, potentially leading to the development of targeted therapies for gastric cancer.


Assuntos
Antineoplásicos , Talaromyces , Talaromyces/química , Humanos , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Cristalografia por Raios X , Produtos Biológicos/farmacologia , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Organismos Aquáticos , Espectroscopia de Ressonância Magnética , Policetídeos/farmacologia , Policetídeos/química , Policetídeos/isolamento & purificação , Estrutura Molecular
2.
Med Mycol ; 62(6)2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38935909

RESUMO

The World Health Organization, in response to the growing burden of fungal disease, established a process to develop a fungal pathogen priority list. This systematic review aimed to evaluate the epidemiology and impact of infections caused by Talaromyces marneffei, Coccidioides species, and Paracoccidioides species. PubMed and Web of Sciences databases were searched to identify studies published between 1 January 2011 and 23 February 2021 reporting on mortality, complications and sequelae, antifungal susceptibility, preventability, annual incidence, and trends. Overall, 25, 17, and 6 articles were included for T. marneffei, Coccidioides spp. and Paracoccidioides spp., respectively. Mortality rates were high in those with invasive talaromycosis and paracoccidioidomycosis (up to 21% and 22.7%, respectively). Hospitalization was frequent in those with coccidioidomycosis (up to 84%), and while the duration was short (mean/median 3-7 days), readmission was common (38%). Reduced susceptibility to fluconazole and echinocandins was observed for T. marneffei and Coccidioides spp., whereas >88% of T. marneffei isolates had minimum inhibitory concentration values ≤0.015 µg/ml for itraconazole, posaconazole, and voriconazole. Risk factors for mortality in those with talaromycosis included low CD4 counts (odds ratio 2.90 when CD4 count <200 cells/µl compared with 24.26 when CD4 count <50 cells/µl). Outbreaks of coccidioidomycosis and paracoccidioidomycosis were associated with construction work (relative risk 4.4-210.6 and 5.7-times increase, respectively). In the United States of America, cases of coccidioidomycosis increased between 2014 and 2017 (from 8232 to 14 364/year). National and global surveillance as well as more detailed studies to better define sequelae, risk factors, outcomes, global distribution, and trends are required.


Assuntos
Antifúngicos , Coccidioides , Paracoccidioides , Talaromyces , Organização Mundial da Saúde , Talaromyces/isolamento & purificação , Talaromyces/classificação , Talaromyces/efeitos dos fármacos , Humanos , Paracoccidioides/isolamento & purificação , Paracoccidioides/efeitos dos fármacos , Paracoccidioides/classificação , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Coccidioides/isolamento & purificação , Coccidioides/classificação , Coccidioides/efeitos dos fármacos , Micoses/epidemiologia , Micoses/microbiologia , Micoses/mortalidade , Paracoccidioidomicose/epidemiologia , Paracoccidioidomicose/microbiologia , Paracoccidioidomicose/tratamento farmacológico , Coccidioidomicose/epidemiologia , Coccidioidomicose/microbiologia , Testes de Sensibilidade Microbiana
3.
Phytochemistry ; 223: 114119, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38705266

RESUMO

Six previously undescribed prenylated indole diketopiperazine alkaloids, talaromyines A-F (1-6), were isolated from the marine-derived fungus Talaromyces purpureogenus SCSIO 41517. Their structures including absolute configurations were elucidated on the basis of comprehensive spectroscopic data including NMR, HR-ESI-MS, and electronic circular dichroism calculations, together with chemical analysis of hydrolysates. Compounds 1-5 represent the first example of spirocyclic indole diketopiperazines biosynthesized from the condensation of L-tryptophan and L-alanine. Compounds 2 and 4-5 showed selective inhibitory activities against phosphatases TCPTP and MEG2 with IC50 value of 17.9-29.7 µM, respectively. Compounds 4-5 exhibited mild cytotoxic activities against two human cancer cell lines H1975 and HepG-2.


Assuntos
Dicetopiperazinas , Talaromyces , Talaromyces/química , Dicetopiperazinas/química , Dicetopiperazinas/farmacologia , Dicetopiperazinas/isolamento & purificação , Humanos , Estrutura Molecular , Prenilação , Ensaios de Seleção de Medicamentos Antitumorais , Relação Estrutura-Atividade , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Alcaloides Indólicos/isolamento & purificação , Alcaloides Indólicos/química , Alcaloides Indólicos/farmacologia , Alcaloides/química , Alcaloides/farmacologia , Alcaloides/isolamento & purificação , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Células Hep G2 , Proliferação de Células/efeitos dos fármacos , Monoéster Fosfórico Hidrolases/antagonistas & inibidores , Monoéster Fosfórico Hidrolases/metabolismo , Linhagem Celular Tumoral
4.
J Nat Prod ; 87(5): 1407-1415, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38662578

RESUMO

Alkaloids with a phenylhydrazone architecture are rarely found in nature. Four unusual phenylhydrazone alkaloids named talarohydrazones A-D (1-4) were isolated from the deep-sea cold seep derived fungus Talaromyces amestolkiae HDN21-0307 using the one strain-many compounds (OSMAC) approach and MS/MS-based molecular networking (MN) combined with network annotation propagation (NAP) and the unsupervised substructure annotation method MS2LDA. Their structures were elucidated by spectroscopic data analysis, single-crystal X-ray diffraction, and quantum chemical calculations. Talarohydrazone A (1) possessed an unusual skeleton combining 2,4-pyridinedione and phenylhydrazone. Talarohydrazone B (2) represents the first natural phenylhydrazone-bearing azadophilone. Bioactivity evaluation revealed that compound 1 exhibited cytotoxic activity against NCI-H446 cells with an IC50 value of 4.1 µM. In addition, compound 1 displayed weak antibacterial activity toward Staphylococcus aureus with an MIC value of 32 µg/mL.


Assuntos
Alcaloides , Hidrazonas , Testes de Sensibilidade Microbiana , Staphylococcus aureus , Talaromyces , Talaromyces/química , Hidrazonas/farmacologia , Hidrazonas/química , Alcaloides/farmacologia , Alcaloides/química , Alcaloides/isolamento & purificação , Estrutura Molecular , Staphylococcus aureus/efeitos dos fármacos , Humanos , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Ensaios de Seleção de Medicamentos Antitumorais , Cristalografia por Raios X
5.
Mycoses ; 67(4): e13726, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38644511

RESUMO

INTRODUCTION: Dimorphic fungi cause infection following the inhalation of spores into the pulmonary system. In the lower respiratory tract, the conidia transform into yeasts, which are engulfed by alveolar macrophages and may be destroyed without disease manifestation. However, in some immunocompromised individuals, they may persist and cause active fungal disease characterized by formation of granulomas in the infected tissues, which may mimic Mycobacterium tuberculosis (MTB). OBJECTIVE: To determine the prevalence of pulmonary dimorphic fungal infections among HIV/AIDS patients with non-TB chronic cough at Mulago National Referral and Teaching Hospital in Kampala, Uganda. METHODS: Sputum samples were collected from 175 consented HIV/AIDS patients attending the immuno-suppression syndrome (ISS) clinic at the hospital. Upon Xpert MTB/RIF sputum testing, 21 patients tested positive for MTB, and these were excluded from further analysis. The other 154 sputum negative samples were then subjected to PCR for dimorphic fungi at MBN Clinical Laboratories. Singleplex PCR was used to detect the target sequences in selected respective genes of each dimorphic fungal species of interest. DNA amplicons were detected based on gel electrophoresis. RESULTS: Dimorphic fungi were detected in 16.2% (25/154) of the studied population. Of these 9.1% (14/154) had Blastomyces dermatitidis and 7.1% (11/154) had Talaromyces marneffei. The remaining 84% of the studied participants had no dimorphic fungi. Histoplasma capsulatum, Coccidioides immitis and Paracoccidioides brasiliensis were not detected in any of the participants. CONCLUSION: Dimorphic fungi (B. dermatitidis and T. marneffei) were found in 16.2% of the HIV/AIDS patients with non-TB chronic cough in Kampala, Uganda. We recommend routine testing for these pathogens among HIV/AIDS patients with chronic cough.


Assuntos
Tosse , Infecções por HIV , Escarro , Humanos , Uganda/epidemiologia , Masculino , Feminino , Adulto , Tosse/microbiologia , Escarro/microbiologia , Pessoa de Meia-Idade , Prevalência , Infecções por HIV/complicações , Infecções por HIV/microbiologia , Doença Crônica , Pneumopatias Fúngicas/microbiologia , Pneumopatias Fúngicas/epidemiologia , Pneumopatias Fúngicas/diagnóstico , Talaromyces/isolamento & purificação , Talaromyces/genética , Adulto Jovem , Estudos Transversais , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Tosse Crônica
6.
J Nat Prod ; 87(4): 1230-1234, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38626456

RESUMO

Three new cyclic heptapeptides, talaromides A-C (1-3), were isolated from cultures produced by the fungus Talaromyces siglerae (Ascomycota), isolated from an unidentified sponge. The structures, featuring an unusual proline-anthranilic moiety, were elucidated by analysis of spectroscopic data and chemical transformations, including the advanced Marfey's method and GITC derivatization. Talaromides A and B inhibited migration activity against PANC-1 human pancreatic cancer cells without significant cytotoxicity.


Assuntos
Peptídeos Cíclicos , Poríferos , Talaromyces , Talaromyces/química , Animais , Poríferos/microbiologia , Humanos , Estrutura Molecular , Peptídeos Cíclicos/farmacologia , Peptídeos Cíclicos/química , Peptídeos Cíclicos/isolamento & purificação , Ensaios de Seleção de Medicamentos Antitumorais , Biologia Marinha , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação
7.
Mar Drugs ; 22(4)2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38667803

RESUMO

Three novel meroterpenoids, taladrimanins B-D (1-3), were isolated from the marine-derived fungus Talaromyces sp. M27416, alongside three biogenetically related compounds (4-6). We delineated taladrimanin B's (1) structure using HRESIMS and NMR, confirmed its configuration via quantum chemical NMR analysis and DP4+ methodology, and verified it through X-ray crystallography. ECD calculations determined the absolute configuration of compound 1, while comparative NMR and ECD analyses elucidated the absolute configurations of 2 and 3. These compounds are drimane-type meroterpenoids with a C10 polyketide unit (8R-configuration). We proposed a biosynthetic pathway and noted that compound 1 showed cytotoxic activity against MKN-45 and 5637 cell lines and selective antibacterial effects against Staphylococcus aureus CICC 10384.


Assuntos
Antibacterianos , Staphylococcus aureus , Talaromyces , Terpenos , Talaromyces/química , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Humanos , Linhagem Celular Tumoral , Staphylococcus aureus/efeitos dos fármacos , Terpenos/farmacologia , Terpenos/química , Terpenos/isolamento & purificação , Cristalografia por Raios X , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Testes de Sensibilidade Microbiana , Organismos Aquáticos , Estrutura Molecular , Espectroscopia de Ressonância Magnética
8.
Eur J Med Chem ; 269: 116314, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38527379

RESUMO

OSMAC strategy is a useful tool for discovering series of metabolites from microorganism. Five new sambutoxin derivatives (1-2, 4, 8-9), together with seven known compounds (3, 5-7, 10-12), were isolated from Talaromyces sp. CY-3 under OSMAC strategy and guidance of molecular networking. Their planar structures and absolute configurations were determined by NMR, HRESIMS, ECD spectra and common biosynthetic pathway. In bioassay, compounds 1-12 showed cytotoxicity to tumor cell lines with IC50 values in the range of 1.76-49.13 µM. The antitumor molecular mechanism of 10 was also explored. In vitro compound 10 significantly inhibited the growth and proliferation of two lung cancer cell lines (A549 and H1703). Furthermore, colony formation, EdU analysis, flow cytometry and Western blot analysis showed that 10 could induce cell cycle arrest in G0/G1 phase by promoting the expression of p53 and p21. The molecular mechanism of its antitumor effects in vitro is that 10 arrests the cell cycle by activating the p21/CyclinD1/Rb signaling pathway and the p53 pathway. Our results identified a lead small molecule compound with efficient antitumor growth and proliferation activity.


Assuntos
Antineoplásicos , Piridinas , Talaromyces , Talaromyces/química , Antineoplásicos/química , Proteína Supressora de Tumor p53 , Linhagem Celular Tumoral , Estrutura Molecular
9.
Phytopathology ; 114(3): 618-629, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37889191

RESUMO

The dynamic of plant-parasitic nematode populations in soil is closely related to soil microorganisms. Fungi from Heterodera zeae cysts were isolated to explore the phenomenon of decline in the H. zeae population in the soil. Phylogenetic study of partial ITS, BenA, CaM, and RPB2 gene sequences, in addition to morphological investigations, was utilized to identify a nematode-destroying fungus. The nematicidal activity of a novel strain GX1 against H. zeae was assessed in vitro and in the greenhouse. Our findings revealed that strain GX1 is a new species of Talaromyces, named Talaromyces cystophila. It has a strong parasitic and lethal effect on H. zeae cysts, with 91.11% parasitism on cysts at 3 days after treatment. The contents of second-stage juveniles (J2s) and eggs inside the cysts were degraded and formed dense vacuoles, and the damaged eggs could not hatch normally. The spore suspension exhibited high nematophagous activity against nematodes, and fermentation filtrate exhibited marked inhibition of egg hatching and nematicidal activities on J2s. The hatching inhibition rates of eggs exposed to 1 × 108 CFU/ml spore suspensions or 20% 1-week fermentation filtrate (1-WF) for 15 days were 98.56 and 100%, respectively. The mortality of J2s exposed to 1 × 108 CFU/ml spore suspension reached 100% at 24 h; exposure to 50% 2-WF was 98.65 and 100% at 24 and 48 h, respectively. Greenhouse experiments revealed that the spore suspension and fermentation broth considerably decreased H. zeae reproduction by 56.17 to 78.76%. T. cystophila is a potential biocontrol strain with nematophagous and nematicidal activity that deserves attention and application.


Assuntos
Cistos , Talaromyces , Tylenchida , Tylenchoidea , Animais , Zea mays , Talaromyces/metabolismo , Filogenia , Doenças das Plantas/prevenção & controle , Doenças das Plantas/parasitologia , Antinematódeos/farmacologia , Solo
10.
Molecules ; 28(23)2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-38067576

RESUMO

Two new dipyrroloquinones, namely talaroterreusinones A (1) and B (2), together with four known secondary metabolites, terreusinone A (3), penicillixanthone A (4), isorhodoptilometrin (5), and chrysomutanin (6), were isolated from the solid culture of the endophytic fungus Talaromyces sp. by integrating mass spectrometry-based metabolic profiling and a bioassay-guided method. Their planar structures and stereochemistry were elucidated by comprehensive spectroscopic analysis including NMR and MS. The absolute configuration at C-1″ of terreusinone A (1) was established by applying the modified Mosher's method. Compounds 1-6 were evaluated for anti-inflammatory activity and cytotoxicity. As a result, 1-3 inhibited the LPS-stimulated NO production in macrophage RAW264.7 cells, with IC50 values of 20.3, 30.7, and 20.6 µM, respectively. Penicillixanthone A (4) exhibited potent cytotoxic activity against Hep G2 and A549 cell lines, with IC50 values of 117 nM and 212 nM, respectively, and displayed significant antitumour effects in A549 cells by inhibiting the PI3K-Akt-mTOR signalling pathway.


Assuntos
Policetídeos , Talaromyces , Estrutura Molecular , Talaromyces/química , Fosfatidilinositol 3-Quinases
11.
J Nat Prod ; 86(9): 2081-2090, 2023 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-37676247

RESUMO

Nine new ergosteroids (1-9) and seven known ones (10-16) were isolated from Talaromyces adpressus. Their structures and absolute configurations were determined by the interpretation of NMR spectroscopic data, HRESIMS, ECD calculations, and single-crystal X-ray diffraction analyses. Structurally, compound 1 was an ergosteroid with two epoxy and a 3α-OH group at ring A, while compounds 8 and 9 had a contracted ring A with a peroxy bridge between C-3 and C-9, which were reported for the first time. Compounds 2-6, 9, 11, and 15 displayed cytotoxic activities with IC50 values ranging from 0.4 to 32 µM, and compound 7 exhibited an immunosuppressive effect against LPS-induced B lymphocyte proliferation with an IC50 value of 8.6 µM. The structure-activity relationships of these compounds are briefly discussed.


Assuntos
Antineoplásicos , Talaromyces , Proliferação de Células , Cristalografia por Raios X
12.
Curr Microbiol ; 80(11): 346, 2023 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-37733094

RESUMO

Endophytes play essential roles in plant growth under metal(loid)s stress. An endophytic fungus strain MR1 was isolated from the roots of Miscanthus floridulus collected from a lead-zinc mining area (Huayuan, China), which could produce indole-3-acetic acid and have Cadmium (Cd) tolerance. Further 18S rRNA sequencing analysis showed that it was highly similar (99.83%) to Talaromyces pinophilus. In pot experiments, we explored the effects of strain MR1 on the growth and Cd uptake of a wide-type Arabidopsis thaliana under low (LC) and high (HC) Cd concentrations. The results showed that MR1 effectively increased the dry weight of aboveground and underground tissues by 25.95-107.21% in both LC and HC groups. Due to MR1 inoculation, the Cd content in the underground tissues was significantly (p < 0.05) decreased by 39.28% under low Cd concentration, while it was significantly (p < 0.05) increased by 28.28% under high Cd concentration. Besides, MR1 inoculations significantly (p < 0.05) increased the total content of removed Cd (17.080 µg) and BCF (0.064) by 129.77% and 153.95% under high Cd concentration. Therefore, we speculated that MR1 might be selected as the effective microbial agent to increase crop yield and control Cd content in the crop in light Cd-contaminated soil. Besides, MR1 could potentially enhance the phytoremediation efficiency of extremely Cd-contaminated soil.


Assuntos
Arabidopsis , Talaromyces , Cádmio/toxicidade , Talaromyces/genética , Transporte Biológico , Solo
13.
Med Mycol ; 61(8)2023 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-37553136

RESUMO

Talaromyces marneffei (TSM) is a temperature-dependent dimorphic fungus endemic to Southeast Asia and southern China. As the number of people at risk of TSM infection continues to increase, the clinical manifestations are becoming increasingly complex, posing challenges for clinical management. In this study, we analyzed the medical records of 99 patients (71 human immunodeficiency virus [HIV]-positive and 28 HIV-negative) diagnosed with TSM infection from January 1, 2017, to December 31, 2022, in southern China and compared the clinical manifestations in HIV-positive and HIV-negative patients. Most patients (83/99, 84%) were male. The incidence of skin and soft tissue involvement (48% vs. 21%, P = .016); disseminated infection with blood circulation, hematopoietic, lymphatic, alimentary, or central nervous system involvement (69% vs. 36%, P = .002); and gastrointestinal bleeding (33% vs. 9%, P = .023) was higher in the HIV-positive group than the HIV-negative group. The HIV-positive group also had significantly higher alanine aminotransferase (ALT) levels (31 [26-42] vs. 14 [11-16] U/l, P < .001) and ALT/aspartate transaminase ratio (1.9 [1.5-2.2] vs. 1.3 [1.1-1.6], P = .006) than the HIV-negative group. The time to diagnosis (5.5 ± 1.1 vs. 5.1 ± 1.4 days, P = .103), antifungal regimen (P = .278), case fatality rate (20% vs. 21%, P = .849), and relapse/reinfection rate (11% vs. 19%, P = .576) did not differ significantly between the HIV-positive and HIV-negative groups. Poor antiretroviral therapy adherence (OR = 26.19, 95%CI 3.26-210.70, P = .002), advanced age (OR = 1.13, 95%CI 1.03-1.23, P = .010), and Epstein-Barr virus co-infection (OR = 37.13, 95%CI 3.03-455.64, P = .005) were independent risk factors for all-cause mortality from TSM infection in HIV-positive patients. Overall, the predominant infection sites, clinical manifestations, and complications of TSM infection differed by HIV status. However, with prompt diagnosis and appropriate treatment, HIV-positive patients with TSM infection can have similar outcomes to HIV-negative patients.


There are certain differences in the clinical features, sites of infection, and associated complications of Talaromyces marneffei infection between individuals with and without human immunodeficiency virus. It is necessary to accurately identify individuals at high risk to enable prompt diagnosis and standardized treatment.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS , Infecções por Vírus Epstein-Barr , Infecções por HIV , Talaromyces , Animais , Humanos , Masculino , Feminino , Estudos Retrospectivos , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Infecções Oportunistas Relacionadas com a AIDS/veterinária , Infecções por Vírus Epstein-Barr/induzido quimicamente , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Infecções por Vírus Epstein-Barr/veterinária , Herpesvirus Humano 4 , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/veterinária , Antifúngicos/uso terapêutico , China/epidemiologia
14.
Sci Rep ; 13(1): 13888, 2023 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-37620377

RESUMO

Talaromyces marneffei is a human fungal pathogen that causes endemic opportunistic infections, especially in Southeast Asia. The key virulence factors of T. marneffei are the ability to survive host-derived heat and oxidative stress, and the ability to convert morphology from environmental mold to fission yeast forms during infection. Glutathione metabolism plays an essential role in stress response and cellular development in multiple organisms. However, the role of the glutathione system in T. marneffei is elusive. Here, we identified the genes encoding principal enzymes associated with glutathione metabolism in T. marneffei, including glutathione biosynthetic enzymes (Gcs1 and Gcs2), glutathione peroxidase (Gpx1), glutathione reductase (Glr1), and a family of glutathione S-transferase (Gst). Sequence homology search revealed an extended family of the TmGst proteins, consisting of 20 TmGsts that could be divided into several classes. Expression analysis revealed that cells in conidia, mold, and yeast phases exhibited distinct expression profiles of glutathione-related genes. Also, TmGst genes were highly upregulated in response to hydrogen peroxide and xenobiotic exposure. Altogether, our findings suggest that T. marneffei transcriptionally regulates the glutathione genes under stress conditions in a cell-type-specific manner. This study could aid in understanding the role of glutathione in thermal-induced dimorphism and stress response.


Assuntos
Estresse Oxidativo , Talaromyces , Humanos , Estresse Oxidativo/genética , Talaromyces/genética , Glutationa , Expressão Gênica
15.
Front Cell Infect Microbiol ; 13: 1163846, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37469600

RESUMO

Background: Sepsis is a life-threatening condition caused by a dysfunctional response to infection from the host. Septic shock, a subset of sepsis, caused by Talaromyces marneffei infection (talaromycosis) has rarely been reported. Owing to its slow culture and low yield, talaromycosis is typically misdiagnosed in HIV-negative patients as other infections, such as tuberculosis, bacterial pneumonia, and lung cancer, especially in non-endemic regions. Early and accurate diagnosis as well as efficient treatment options are required to improve prognosis. Method: A 30-year-old HIV-negative Chinese woman from a non-endemic area of T. marneffei was initially misdiagnosed with tuberculosis. She had a poor response to anti-tuberculosis treatment. On July 16, 2022, she was admitted to our hospital; the patient developed septic shock on the third day after hospitalization and was ultimately diagnosed with talaromycosis via metagenomic next-generation sequencing (mNGS). Result: The condition of the patient improved after appropriate treatment with amphotericin B. Furthermore, enzyme-linked immunosorbent assay results confirmed that the patient had a high-titer of anti-interferon gamma (IFN-γ) autoantibodies. Conclusion: HIV-negative individuals with anti-IFN-γ autoantibodies typically have relapsing, refractory, and fatal infections, such as talaromycosis, which is typically misdiagnosed in the initial course of the disease. This can lead to septic shock. Clinicians should be aware that they may encounter HIV-negative patients with T. marneffei infection in non-endemic areas. Thus, mNGS is an effective technology for detecting T. marneffei infection. Additionally, the detection of anti-IFN-γ autoantibodies in these patients would aid in knowing their susceptibility to fatal infections.


Assuntos
Micoses , Sepse , Choque Séptico , Adulto , Feminino , Humanos , Antifúngicos/uso terapêutico , Autoanticorpos , Sequenciamento de Nucleotídeos em Larga Escala , Interferon gama , Recidiva Local de Neoplasia/tratamento farmacológico , Sepse/tratamento farmacológico , Choque Séptico/diagnóstico , Talaromyces , Soronegatividade para HIV , Micoses/diagnóstico
16.
Front Immunol ; 14: 1192326, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37457708

RESUMO

Pathogenic eukaryotes including fungi release extracellular vesicles (EVs) which are composed of a variety of bioactive components, including peptides, nucleic acids, polysaccharides, and membrane lipids. EVs contain virulence-associated molecules suggesting a crucial role of these structures in disease pathogenesis. EVs derived from the pathogenic yeast phase of Talaromyces (Penicillium) marneffei, a causative agent of systemic opportunistic mycoses "talaromycosis," were studied for their immunogenic components and immunomodulatory properties. Some important virulence factors in EVs including fungal melanin and yeast phase specific mannoprotein were determined by immunoblotting. Furthermore, fluorescence microscopy revealed that T. marneffei EVs were internalized by THP-1 human macrophages. Co-incubation of T. marneffei EVs with THP-1 human macrophages resulted in increased levels of supernatant interleukin (IL)-1ß, IL-6 and IL-10. The expression of THP-1 macrophage surface CD86 was significantly increased after exposed to T. marneffei EVs. These findings support the hypothesis that fungal EVs play an important role in macrophage "classical" M1 polarization. T. marneffei EVs preparations also increased phagocytosis, suggesting that EV components stimulate THP-1 macrophages to produce effective antimicrobial compounds. In addition, T. marneffei EVs stimulated THP-1 macrophages were more effective at killing T. marneffei conidia. These results indicate that T. marneffei EVs can potently modulate macrophage functions, resulting in the activation of these innate immune cells to enhance their antimicrobial activity.


Assuntos
Vesículas Extracelulares , Talaromyces , Humanos , Saccharomyces cerevisiae , Macrófagos , Vesículas Extracelulares/metabolismo
18.
Chem Biol Drug Des ; 102(5): 1308-1326, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37246452

RESUMO

In recent years, there has been a lot of buzz about the possibilities of marine microflora as a source of new therapeutic drugs. The strong anti-tumor potency of compounds found in marine resources reflects the ocean's enormous potential as a source of anticancer therapeutics. In this present investigation, an ambuic acid derivative anticancer compound was isolated from Talaromyces flavus, and its cytotoxicity and apoptosis induction potential were analyzed. T. flavus was identified through morphological and molecular analysis. The various organic solvent extracts of T. flavus grown on different growth mediums were evaluated for cytotoxicity on different cancer cell lines. The potent cytotoxicity was shown in the ethyl acetate extract of a fungal culture grown in the M1-D medium for 21 days. Furthermore, the anticancer compound was identified using preparative thin layer chromatography, followed by its purification in significant proportions using column chromatography. The spectroscopic and chromatographic analysis revealed that the structure of the purified molecules was an ambuic acid derivative. The ambuic acid derivative compound showed potent cytotoxicity on MDA-MB-231 (breast cancer cells) with an IC50 value of 26 µM and induced apoptosis in the MDA-MB-231 cells in a time-dependent and reactive oxygen species-independent manner.


Assuntos
Neoplasias , Talaromyces , Linhagem Celular Tumoral , Talaromyces/química , Apoptose
19.
Microb Pathog ; 181: 106168, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37224982

RESUMO

Macrophage-derived inflammatory cytokines are critical for host defense against Talaromyces marneffei (T. marneffei) infection among HIV/AIDS patients, and excessive inflammatory cytokines are associated with poor outcomes of AIDS-associated talaromycosis. However, the underlying mechanisms of macrophage-caused pyroptosis and cytokine storm are poorly understood. Here, in the T. marneffei-infected mice and macrophages, we show that T. marneffei induced pyroptosis in macrophages through the NLRP3/caspase-1 pathway. The immunomodulatory drug thalidomide could promote the pyroptosis of macrophages infected T. marneffei. In T. marneffei-infected mice, the splenic macrophages underwent increasing pyroptosis as talaromycosis deteriorated. Thalidomide ameliorated inflammation of mice, while amphotericin B (AmB) in combination with thalidomide did not improve overall survival compared with AmB alone. Taken together, our findings suggest that thalidomide promotes NLRP3/caspase-1-mediated pyroptosis of macrophages in T. marneffei infection.


Assuntos
Talaromyces , Talidomida , Animais , Camundongos , Talidomida/farmacologia , Talidomida/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Caspase 1/metabolismo , Piroptose , Macrófagos/metabolismo , Anfotericina B , Citocinas/metabolismo
20.
Appl Microbiol Biotechnol ; 107(11): 3699-3716, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37083969

RESUMO

Fungal colorants are gradually entering the global color market, given their advantages of being less harmful to human health, as well as having greater stability and biotechnological potential, compared to other natural sources. The present work concerns the isolation and identification of an endophytic filamentous fungus, together with the chemical characterization and assessment of the fluorescence, toxicity, stability, and application potential of its synthesized red colorant. The endophytic fungus was isolated from Hymenaea courbaril, a tree from the Brazilian savannah, and was identified as Talaromyces minnesotensis by phenotypic and genotypic characterization. Submerged cultivation of the fungus resulted in the production of approximately 12 AU500 of a red biocolorant which according to LC-DAD-MS analysis is characterized by being a complex mixture of molecules of the azaphilone class. Regarding cytotoxicity assays, activity against human hepatoblastoma (HepG2) cells was only observed at concentrations above 5.0 g L-1, while antimicrobial effects against pathogenic bacteria and yeast occurred at concentrations above 50.0 g L-1. The biocolorant showed high stability at neutral pH values and low temperatures (10 to 20 °C) and high half-life values (t1/2), which indicates potential versatility for application in different matrices, as observed in tests using detergent, gelatin, enamel, paint, and fabrics. The results demonstrated that the biocolorant synthesized by Talaromyces minnesotensis has potential for future biotechnological applications. KEY POINTS: • An endophytic fungus, which was isolated and identified, synthesize a red colorant. • The colorant showed fluorescence property, low toxicity, and application potential. • The red biocolorant was highly stable at pH 8.0 and temperatures below 20°C.


Assuntos
Talaromyces , Humanos , Temperatura , Temperatura Baixa , Alimentos , Concentração de Íons de Hidrogênio , Saccharomyces cerevisiae
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