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1.
Einstein (Sao Paulo) ; 22: eAO0138, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38775603

RESUMO

OBJECTIVE: This study aimed to verify oral candidiasis, identify the causative species, and investigate the antifungal susceptibility of yeasts isolated from liver transplant patients. METHODS: A descriptive analysis of 97 patients who underwent liver transplantation was conducted at a hospital. Two clinical examinations (Collections A and B) of the oral cavity were performed. Oral material was collected from all patients, inoculated in Sabouraud Dextrose Agar, and incubated at 35℃ for 48 hours. Samples were identified by molecular sequencing of the internal trascribed space region of rDNA. RESULTS: An antifungal susceptibility test with fluconazole, amphotericin B, and micafungin was performed using the Clinical and Laboratory Standards Institute yeast broth microdilution method. Among the patients, 15 presented with oral candidiasis: eight in Collection A and seven in Collection B. The primary type of candidiasis was atrophic, followed by pseudomembranous candidiasis. The most prevalent species was Candida albicans (nine), followed by Candida glabrata (three), Candida tropicalis (two), and Candida dubliniensis (one). Regarding susceptibility to fluconazole, of the 15 samples, 11 were susceptible, three were susceptible in a dose-dependent manner, and one was resistant. CONCLUSION: The most commonly identified type of candidiasis was atrophic, with C. albicans and C. glabrata being the most prevalent causative species. One fluconazole-resistant isolate each of C. tropicalis and C. albicans were identified.


Assuntos
Antifúngicos , Candida , Candidíase Bucal , Fluconazol , Transplante de Fígado , Testes de Sensibilidade Microbiana , Humanos , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Transplante de Fígado/efeitos adversos , Masculino , Candidíase Bucal/microbiologia , Candidíase Bucal/tratamento farmacológico , Feminino , Pessoa de Meia-Idade , Candida/efeitos dos fármacos , Candida/classificação , Candida/isolamento & purificação , Fluconazol/farmacologia , Adulto , Anfotericina B/farmacologia , Idoso , Farmacorresistência Fúngica , Micafungina/farmacologia , Micafungina/uso terapêutico , Adulto Jovem
2.
Cell Host Microbe ; 32(5): 625-626, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38723598

RESUMO

Fungi colonize the mammalian gastrointestinal (GI) tract and can adopt both commensal and opportunistic lifestyles. In a recent issue of Nature, Liang et al. unraveled the complex interplay between Candida morphotypes and the gut bacterial microbiota and described a key role for candidalysin in gut colonization.1.


Assuntos
Candida , Microbioma Gastrointestinal , Trato Gastrointestinal , Simbiose , Microbioma Gastrointestinal/fisiologia , Humanos , Trato Gastrointestinal/microbiologia , Animais , Candida/fisiologia , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/genética
3.
J Insect Sci ; 24(3)2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38713543

RESUMO

The black soldier fly, Hermetia illucens L. (Diptera: Stratiomyidae), is commonly used for organic waste recycling and animal feed production. However, the often inadequate nutrients in organic waste necessitate nutritional enhancement of black soldier fly larvae, e.g., by fungal supplementation of its diet. We investigated the amino acid composition of two fungi, Candida tropicalis (Castell.) Berkhout (Saccharomycetales: Saccharomycetaceae) and Pichia kudriavzevii Boidin, Pignal & Besson (Saccharomycetales: Pichiaceae), from the black soldier fly gut, and commercial baker's yeast, Saccharomyces cerevisiae Meyen ex E.C. Hansen (Saccharomycetales: Saccharomycetaceae), and their effects on larval growth and hemolymph metabolites in fifth-instar black soldier fly larvae. Liquid chromatography-mass spectrometry was used to study the effect of fungal metabolites on black soldier fly larval metabolism. Amino acid analysis revealed significant variation among the fungi. Fungal supplementation led to increased larval body mass and differential metabolite accumulation. The three fungal species caused distinct metabolic changes, with each over-accumulating and down-accumulating various metabolites. We identified significant alteration of histidine metabolism, aminoacyl-tRNA biosynthesis, and glycerophospholipid metabolism in BSF larvae treated with C. tropicalis. Treatment with P. kudriavzevii affected histidine metabolism and citrate cycle metabolites, while both P. kudriavzevii and S. cerevisiae treatments impacted tyrosine metabolism. Treatment with S. cerevisiae resulted in down-accumulation of metabolites related to glycine, serine, and threonine metabolism. This study suggests that adding fungi to the larval diet significantly affects black soldier fly larval metabolomics. Further research is needed to understand how individual amino acids and their metabolites contributed by fungi affect black soldier fly larval physiology, growth, and development, to elucidate the interaction between fungal nutrients and black soldier fly physiology.


Assuntos
Dípteros , Hemolinfa , Larva , Animais , Larva/crescimento & desenvolvimento , Larva/metabolismo , Dípteros/metabolismo , Dípteros/crescimento & desenvolvimento , Hemolinfa/metabolismo , Pichia/metabolismo , Saccharomyces cerevisiae/metabolismo , Aminoácidos/metabolismo , Dieta , Saccharomycetales/metabolismo , Ração Animal/análise , Candida/metabolismo , Candida/crescimento & desenvolvimento
4.
Arch Microbiol ; 206(6): 257, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38734773

RESUMO

There is a growing imperative for research into alternative compounds for the treatment of the fungal infections. Thus, many studies have focused on the analysis of antifungal proteins and peptides from different plant sources. Among these molecules are protease inhibitors (PIs). Previously, PIs present in the peptide-rich fractions called PEF1, PEF2 and PEF3 were identified from Capsicum chinense seeds, which have strong activity against phytopathogenic fungi. The aim of this study was to evaluate the mechanism of action and antimicrobial activity of PIs from PEF2 and PEF3 on the growth of yeasts of the genus Candida. In this work, analyses of their antimicrobial activity and cell viability were carried out. Subsequently, the mechanism of action by which the PIs cause the death of the yeasts was evaluated. Cytotoxicity was assessed in vitro by erythrocytes lysis and in vivo in Galleria mellonella larvae. PEF2 and PEF3 caused 100% of the growth inhibition of C. tropicalis and C. buinensis. For C. albicans inhibition was approximately 60% for both fractions. The PEF2 and PEF3 caused a reduction in mitochondrial functionality of 54% and 46% for C. albicans, 26% and 30% for C. tropicalis, and 71% and 68% for C. buinensis, respectively. These fractions induced morphological alterations, led to membrane permeabilization, elevated ROS levels, and resulted in necrotic cell death in C. tropicalis, whilst demonstrating low toxicity toward host cells. From the results obtained here, we intend to contribute to the understanding of the action of PIs in the control of fungal diseases of medical importance.


Assuntos
Antifúngicos , Candida , Inibidores de Proteases , Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Candida/crescimento & desenvolvimento , Inibidores de Proteases/farmacologia , Testes de Sensibilidade Microbiana , Animais , Capsicum/microbiologia , Espécies Reativas de Oxigênio/metabolismo , Sementes/crescimento & desenvolvimento , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Eritrócitos/efeitos dos fármacos , Larva/microbiologia , Larva/crescimento & desenvolvimento , Larva/efeitos dos fármacos
5.
Arch Microbiol ; 206(6): 255, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38734793

RESUMO

Cystic fibrosis (CF) is an inherited disease that results from mutations in the gene responsible for the cystic fibrosis transmembrane conductance regulator (CFTR). The airways become clogged with thick, viscous mucus that traps microbes in respiratory tracts, facilitating colonization, inflammation and infection. CF is recognized as a biofilm-associated disease, it is commonly polymicrobial and can develop in biofilms. This review discusses Candida spp. and both Gram-positive and Gram-negative bacterial biofilms that affect the airways and cause pulmonary infections in the CF context, with a particular focus on mixed-species biofilms. In addition, the review explores the intricate interactions between fungal and bacterial species within these biofilms and elucidates the underlying molecular mechanisms that govern their dynamics. Moreover, the review addresses the multifaceted issue of antimicrobial resistance in the context of CF-associated biofilms. By synthesizing current knowledge and research findings, this review aims to provide insights into the pathogenesis of CF-related infections and identify potential therapeutic approaches to manage and combat these complex biofilm-mediated infections.


Assuntos
Biofilmes , Candida , Fibrose Cística , Biofilmes/crescimento & desenvolvimento , Fibrose Cística/microbiologia , Humanos , Candida/fisiologia , Candida/genética , Candidíase/microbiologia , Bactérias Gram-Negativas/fisiologia , Bactérias Gram-Negativas/genética , Antibacterianos/farmacologia
6.
Int J Mol Sci ; 25(9)2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38731993

RESUMO

Extracellular proteases are key factors contributing to the virulence of pathogenic fungi from the genus Candida. Their proteolytic activities are crucial for extracting nutrients from the external environment, degrading host defenses, and destabilizing the internal balance of the human organism. Currently, the enzymes most frequently described in this context are secreted aspartic proteases (Saps). This review comprehensively explores the multifaceted roles of Saps, highlighting their importance in biofilm formation, tissue invasion through the degradation of extracellular matrix proteins and components of the coagulation cascade, modulation of host immune responses via impairment of neutrophil and monocyte/macrophage functions, and their contribution to antifungal resistance. Additionally, the diagnostic challenges associated with Candida infections and the potential of Saps as biomarkers were discussed. Furthermore, we examined the prospects of developing vaccines based on Saps and the use of protease inhibitors as adjunctive therapies for candidiasis. Given the complex biology of Saps and their central role in Candida pathogenicity, a multidisciplinary approach may pave the way for innovative diagnostic strategies and open new opportunities for innovative clinical interventions against candidiasis.


Assuntos
Ácido Aspártico Proteases , Candidíase , Interações Hospedeiro-Patógeno , Humanos , Ácido Aspártico Proteases/metabolismo , Candidíase/microbiologia , Candida/patogenicidade , Candida/enzimologia , Biofilmes/crescimento & desenvolvimento , Animais , Proteínas Fúngicas/metabolismo
7.
Front Cell Infect Microbiol ; 14: 1295841, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38707510

RESUMO

Introduction: Although the existence of Candida species in the respiratory tract is often considered commensal, it is crucial to recognize the significance of Candida colonization in immunocompromised or COVID-19 patients. The emergence of Candida auris as an emerging pathogen further emphasizes the importance of monitoring yeast infection/colonization, particularly in COVID-19 patients. Methods: In this study, respiratory samples mainly from COVID-19 patients, primarily those suspected of having a fungal infection, were cultured on Sabouraud dextrose agar plates and the yeast colonies were identified using a two-step multiplex PCR method. The samples suspected of C. auris underwent specific nested PCR followed by sequence analysis. Results: A total of 199 respiratory samples were collected from 73 women and 126 men, ranging in age from 1.6 to 88 years. Among the patients, 141 had COVID-19, 32 had cancer, 5 were hospitalized in ICU, 2 had chronic obstructive pulmonary disease)COPD(, and others were patients with combination diseases. From these samples, a total of 334 yeast strains were identified. C. albicans (n=132, 39.52%) was the most common species, followed by C. tropicalis (n=67, 20%), C. glabrata (n=56, 16.76%), C. krusei (n=18, 5.4%), C. parapsilosis (n=17, 5.08%), Saccharomyces cerevisiae (n=10, 3%), C. kefyr (n=9, 2.6%), C. dubliniensis (n=7, 2.1%), C. lusitaniae (n=5, 1.5%), C. auris (n=3, 0.9%), C. guilliermondii (n=2, 0.6%), C. rugosa (n=1, 0.3%), C. intermedia (n=1, 0.3%), and Trichosporon spp. (n=1, 0.3%). C. auris was detected in a patient in ICU and two COVID-19 patients. While its presence was confirmed through sequence analysis, our extensive efforts to isolate C. auris were unsuccessful. Conclusion: While C. albicans colonization remains prevalent, our study found no evidence of Candida lung infection. Since the role of Candida colonization in airway secretions remains ambiguous due to limited research, further studies are imperative to shed light on this matter.


Assuntos
COVID-19 , Candida auris , Candidíase , SARS-CoV-2 , Humanos , COVID-19/microbiologia , Idoso , Pessoa de Meia-Idade , Feminino , Masculino , Idoso de 80 Anos ou mais , Adulto , Pré-Escolar , Candidíase/microbiologia , Criança , Adolescente , Adulto Jovem , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Lactente , Candida auris/genética , Candida auris/isolamento & purificação , Candida/isolamento & purificação , Candida/classificação , Candida/genética , Sistema Respiratório/microbiologia , Sistema Respiratório/virologia , Reação em Cadeia da Polimerase Multiplex
8.
World J Gastroenterol ; 30(16): 2281-2284, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38690016

RESUMO

The following are our views regarding the "letter to the editor" (Helicobacter is preserved in yeast vacuoles! Does Koch's postulates confirm it?) by Alipour and Gaeini, and the response "letter to the editor" (Candida accommodates non-culturable Helicobacter pylori in its vacuole-Koch's postulates aren't applicable) by Siavoshi and Saniee. Alipour and Gaeini rejected the methods, results, discussion, and conclusions summarized in a review article by Siavoshi and Saniee. The present article reviews and discusses evidence on the evolutionary adaptation of Helicobacter pylori (H. pylori) to thrive in Candida cell vacuoles and concludes that Candida could act as a Trojan horse, transporting potentially infectious H. pylori into the stomach of humans.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Helicobacter pylori/patogenicidade , Humanos , Infecções por Helicobacter/microbiologia , Candida/fisiologia , Candida/crescimento & desenvolvimento , Candida/patogenicidade , Vacúolos/microbiologia , Vacúolos/metabolismo , Estômago/microbiologia , Mucosa Gástrica/microbiologia
9.
Rehabil Nurs ; 49(3): E11-E12, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38696437

Assuntos
Candida , Candidíase , Humanos
10.
J Med Microbiol ; 73(5)2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38771623

RESUMO

The emergent fungal pathogen Candida auris is increasingly recognised as an important cause of healthcare-associated infections globally. It is highly transmissible, adaptable, and persistent, resulting in an organism with significant outbreak potential that risks devastating consequences. Progress in the ability to identify C. auris in clinical specimens is encouraging, but laboratory diagnostic capacity and surveillance systems are lacking in many countries. Intrinsic resistance to commonly used antifungals, combined with the ability to rapidly acquire resistance to therapy, substantially restricts treatment options and novel agents are desperately needed. Despite this, outbreaks can be interrupted, and mortality avoided or minimised, through the application of rigorous infection prevention and control measures with an increasing evidence base. This review provides an update on epidemiology, the impact of the COVID-19 pandemic, risk factors, identification and typing, resistance profiles, treatment, detection of colonisation, and infection prevention and control measures for C. auris. This review has informed a planned 2024 update to the United Kingdom Health Security Agency (UKHSA) guidance on the laboratory investigation, management, and infection prevention and control of Candida auris. A multidisciplinary response is needed to control C. auris transmission in a healthcare setting and should emphasise outbreak preparedness and response, rapid contact tracing and isolation or cohorting of patients and staff, strict hand hygiene and other infection prevention and control measures, dedicated or single-use equipment, appropriate disinfection, and effective communication concerning patient transfers and discharge.


Assuntos
Antifúngicos , COVID-19 , Candida auris , Candidíase , Controle de Infecções , Humanos , Candidíase/prevenção & controle , Candidíase/epidemiologia , Candidíase/tratamento farmacológico , Candidíase/microbiologia , Controle de Infecções/métodos , Candida auris/efeitos dos fármacos , COVID-19/prevenção & controle , COVID-19/epidemiologia , Antifúngicos/uso terapêutico , Antifúngicos/farmacologia , Inglaterra/epidemiologia , Infecção Hospitalar/prevenção & controle , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , SARS-CoV-2 , Farmacorresistência Fúngica , Candida/efeitos dos fármacos , Candida/classificação , Candida/isolamento & purificação , Surtos de Doenças/prevenção & controle
11.
Sci Rep ; 14(1): 11597, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773138

RESUMO

Candida is the most prevalent fungal bloodstream infection (BSI) with a high mortality rate among hospitalized patients. Another concern facing physicians is rising global incidence of drug-resistant Candida. This study aimed to characterize the prevalence, antifungal susceptibility, biofilm formation, and virulence genes (HWP1, ALS1, SAP2) of different Candida spp. isolated from patients with candidemia. 52 isolates of Candida spp. were identified from blood cultures by chromogenic Candida agar and confirmed by the VITEK 2 system. Isolates were tested for antifungal susceptibility by disk diffusion and VITEK 2 system. Biofilm formation and investigated genes were detected by the Congo red method and conventional PCR, respectively. Candida spp. caused 2.3% of detected BSIs, of which 32.7% were caused by Candida albicans (C. albicans) and 67.3% by non-albicans Candida (NAC), with the predominance of C. tropicalis (25%), followed by C. parapsilosis (17.3%), and C. krusei (13.5%). The susceptibility rates to fluconazole, voriconazole, caspofungin, micafungin, amphotericin B, and flucytosine were 64.7%, 76.5%, 100.0%, 100%, 100.0%, and 100.0% in C. albicans, while 53.6%, 71.4%, 91.4%, 91.4%, 94.3%, and 94.3% in NAC, respectively. Biofilm production, HWP1, ALS1, and SAP2 were detected in 70.6%, 82.4%, 76.5%, and 52.9% of C. albicans and 74.3%, 85.7%, 80.0%, and 48.6% of NAC, respectively. There is remarkable shift to NAC BSIs and high azole resistance. Antifungal stewardship and analysis of risk factors associated with this shift are needed.


Assuntos
Antifúngicos , Biofilmes , Candida , Candidemia , Farmacorresistência Fúngica , Testes de Sensibilidade Microbiana , Humanos , Candidemia/microbiologia , Candidemia/tratamento farmacológico , Candidemia/epidemiologia , Antifúngicos/farmacologia , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Candida/efeitos dos fármacos , Candida/isolamento & purificação , Candida/patogenicidade , Candida/genética , Fatores de Virulência/genética , Virulência , Feminino , Masculino , Pessoa de Meia-Idade , Adulto
12.
Expert Rev Anti Infect Ther ; 22(5): 289-296, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38720183

RESUMO

INTRODUCTION: In the face of increased frequency of non-albicans Candida vulvovaginitis (VVC) reported worldwide, there is a paucity of effective oral and topical antifungal drugs available. Drug selection is further handicapped by an absence of data of clinical efficacy of available antifungal drugs for these infections. AREAS COVERED: In this review, attention is directed at the cause of drug shortage as well as increased frequency of non-albicans Candida (NAC) vulvovaginitis. There is widespread recognition of reduced in vitro azole drug susceptibility in NAC species. Moreover, antifungal susceptibility tests have not been standardized or validated for NAC isolates, hence clinicians rely on an element of empiricism especially given the absence of randomized controlled comparative studies targeting NAC species. Clinical spectrum of NAC species isolates is highly variable with ongoing difficulty in determining a causal role in symptomatic patients. EXPERT OPINION: We have entered the era of demand for Candida species-specific therapy and although consensus treatment guidelines are emerging, new antifungal agents that target these multiple-azole resistant or relatively resistant vaginal NAC species are urgently needed.


Assuntos
Antifúngicos , Candida , Candidíase Vulvovaginal , Farmacorresistência Fúngica , Testes de Sensibilidade Microbiana , Humanos , Candida/efeitos dos fármacos , Candida/isolamento & purificação , Antifúngicos/administração & dosagem , Antifúngicos/farmacologia , Feminino , Candidíase Vulvovaginal/tratamento farmacológico , Candidíase Vulvovaginal/microbiologia , Azóis/farmacologia , Azóis/administração & dosagem , Especificidade da Espécie , Guias de Prática Clínica como Assunto
13.
J Inorg Biochem ; 256: 112572, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38691971

RESUMO

Recognizing that metal ions play an important role in modifying the pharmacological properties of known organic-based drugs, the present manuscript addresses the complexation of the antifungal agent voriconazole (vcz) with the biologically relevant silver(I) ion as a strategy for the development of new antimycotics. The synthesized silver(I) complexes with vcz were characterized by mass spectrometry, IR, UV-Vis and NMR spectroscopy and single-crystal X-ray diffraction analysis. The crystallographic results showed that complexes {[Ag(vcz)(H2O)]CH3SO3}n (1), {[Ag(vcz)2]BF4}n (2) and {[Ag(vcz)2]PF6}n (3) have polymeric structures in the solid state, in which silver(I) ions have a distorted tetrahedral geometry. On the other hand, DFT calculations revealed that the investigated silver(I) complexes 1-3 in DMSO exist as linear [Ag(vcz-N2)(vcz-N19)]+ (1a), [Ag(vcz-N2)(vcz-N4)]+ (2a) and [Ag(vcz-N4)2]+ (3a) species, respectively. The evaluated complexes showed an enhanced anti-Candida activity compared to the parent drug with minimal inhibitory concentration (MIC) values in the range of 0.02-1.05 µM. In comparison with vcz, the corresponding silver(I) complexes showed better activity in prevention hyphae and biofilm formation of C. albicans, indicating that they could be considered as promising agents against Candida that significantly inhibit its virulence. Also, these complexes are much better inhibitors of ergosterol synthesis in the cell membrane of C. albicans at the concentration of 0.5 × MIC. This is also confirmed by a molecular docking, which revealed that complexes 1a - 3a showed better inhibitory activity than vcz against the sterol 14α-demethylase enzyme cytochrome P450 (CYP51B), which plays a crucial role in the formation of ergosterol.


Assuntos
Antifúngicos , Complexos de Coordenação , Testes de Sensibilidade Microbiana , Prata , Voriconazol , Antifúngicos/farmacologia , Antifúngicos/química , Antifúngicos/síntese química , Voriconazol/farmacologia , Voriconazol/química , Prata/química , Prata/farmacologia , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Candida albicans/efeitos dos fármacos , Candida/efeitos dos fármacos , Cristalografia por Raios X
14.
Sci Rep ; 14(1): 11132, 2024 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-38750088

RESUMO

Candida species have been responsible for a high number of invasive infections worldwide. In this sense, Rottlerin has demonstrated a wide range of pharmacological activities. Therefore, this study aimed to evaluate the antifungal, antibiofilm and antivirulence activity of Rottlerin in vitro against Candida spp. and its toxicity and antifungal activity in vivo. Rottlerin showed antifungal activity against all yeasts evaluated, presenting Minimum Inhibitory and Fungicidal Concentration (MIC and MFC) values of 7.81 to > 1000 µg/mL. Futhermore, it was able to significantly inhibit biofilm production, presenting Biofilm Inhibitory Concentration (MICB50) values that ranged from 15.62 to 250 µg/mL and inhibition of the cell viability of the biofilm by 50% (IC50) from 2.24 to 12.76 µg/mL. There was a considerable reduction in all hydrolytic enzymes evaluated, with emphasis on hemolysin where Rottlerin showed a reduction of up to 20%. In the scanning electron microscopy (SEM) analysis, Rottlerin was able to completely inhibit filamentation by C. albicans. Regarding in vivo tests, Rottlerin did not demonstrate toxicity at the therapeutic concentrations demonstrated here and was able to increase the survival of C. elegans larvae infected. The results herein presented are innovative and pioneering in terms of Rottlerin's multipotentiality against these fungal infections.


Assuntos
Acetofenonas , Antifúngicos , Benzopiranos , Biofilmes , Testes de Sensibilidade Microbiana , Biofilmes/efeitos dos fármacos , Antifúngicos/farmacologia , Benzopiranos/farmacologia , Animais , Acetofenonas/farmacologia , Caenorhabditis elegans/efeitos dos fármacos , Candida/efeitos dos fármacos , Candidíase/tratamento farmacológico , Candida albicans/efeitos dos fármacos
15.
Sci Rep ; 14(1): 11228, 2024 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-38755187

RESUMO

Antimicrobial resistance in fungal pathogens (both human and plant) is increasing alarmingly, leading to massive economic crises. The existing anti-fungal agents are becoming ineffective, and the situation worsens on a logarithmic scale. Novel antifungals from unique natural sources are highly sought to cope sustainably with the situation. Metabolites from endophytic microbes are the best-fitted alternatives in this case. Endophytes are the untapped sources of 'plants' internal microbial population' and are promising sources of effective bio-therapeutic agents. Fungal endophytes were isolated from Tropaeolum majus and checked for antifungal activity against selected plant and human pathogens. Bioactive metabolites were identified through chromatographic techniques. The mode of action of those metabolites was evaluated through various spectroscopic techniques. The production of antifungal metabolite was optimized also. In particular VOCs (volatile organic compounds) of TML9 were tested in vitro for their anti-phytopathogenic activity. Ethyl acetate (EA) extract of cell-free culture components of Colletotrichum aenigma TML3 exhibited broad-spectrum antifungal activity against four species of Candida and the major constituents reported were 6-pentyl-2H-pyran-2-one, 2-Nonanone, 1 propanol 2-amino. The volatile metabolites, trans-ocimene, geraniol, and 4-terpinyl acetate, produced from Curvularia lunata TML9, inhibited the growth of some selected phyto pathogens. EA extract hampered the biofilm formation, minimised the haemolytic effect, and blocked the transformation of Candida albicans (MTCC 4748) from yeast to hyphal form with a Minimum Fungicidal Concentration (MFC) of 200-600 µg mL-1. Central carbohydrate metabolism, ergosterol synthesis, and membrane permeability were adversely affected and caused the lethal leakage of necessary macromolecules of C. albicans. Volatile metabolites inhibited the growth of phytopathogens i.e., Rhizoctonia solani, Alternaria alternata, Botrytis cinerea, Cercospora beticola, Penicillium digitatum, Aspergillus fumigatus, Ceratocystis ulmi, Pythium ultimum up to 89% with an IC50 value of 21.3-69.6 µL 50 mL-1 and caused leakage of soluble proteins and other intracellular molecules. Citrusy sweet odor volatiles of TML9 cultured in wheat-husk minimised the infections of Penicillium digitatum (green mold), in VOC-exposed sweet oranges (Citrus sinensis). Volatile and non-volatile antifungal metabolites of these two T. majus endophytes hold agricultural and pharmaceutical interests. Metabolites of TML3 have strong anti-Candida activity and require further assessment for therapeutic applications. Also, volatile metabolites of TML9 can be further studied as a source of antifungals. The present investigational outcomes bio-prospects the efficacy of fungal endophytes of Garden Nasturtium.


Assuntos
Antifúngicos , Endófitos , Compostos Orgânicos Voláteis , Compostos Orgânicos Voláteis/farmacologia , Compostos Orgânicos Voláteis/química , Antifúngicos/farmacologia , Antifúngicos/química , Endófitos/metabolismo , Endófitos/química , Testes de Sensibilidade Microbiana , Colletotrichum/efeitos dos fármacos , Fungos/efeitos dos fármacos , Alternaria/efeitos dos fármacos , Rhizoctonia/efeitos dos fármacos , Humanos , Candida/efeitos dos fármacos
17.
Life Sci Alliance ; 7(7)2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38719750

RESUMO

Celiac disease (CD) is an autoimmune enteropathy resulting from an interaction between diet, genome, and immunity. Although many patients respond to a gluten-free diet, in a substantive number of individuals, the intestinal injury persists. Thus, other factors might amplify the ongoing inflammation. Candida albicans is a commensal fungus that is well adapted to the intestinal life. However, specific conditions increase Candida pathogenicity. The hypothesis that Candida may be a trigger in CD has been proposed after the observation of similarity between a fungal wall component and two CD-related gliadin T-cell epitopes. However, despite being implicated in intestinal disorders, Candida may also protect against immune pathologies highlighting a more intriguing role in the gut. Herein, we postulated that a state of chronic inflammation associated with microbial dysbiosis and leaky gut are favorable conditions that promote C. albicans pathogenicity eventually contributing to CD pathology via a mast cells (MC)-IL-9 axis. However, the restoration of immune and microbial homeostasis promotes a beneficial C. albicans-MC cross-talk favoring the attenuation of CD pathology to alleviate CD pathology and symptoms.


Assuntos
Candida albicans , Doença Celíaca , Homeostase , Mastócitos , Doença Celíaca/imunologia , Doença Celíaca/microbiologia , Doença Celíaca/metabolismo , Humanos , Candida albicans/patogenicidade , Candida albicans/imunologia , Mastócitos/imunologia , Mastócitos/metabolismo , Microbioma Gastrointestinal/imunologia , Disbiose/imunologia , Candidíase/imunologia , Candidíase/microbiologia , Animais , Candida/patogenicidade , Candida/imunologia , Mucosa Intestinal/microbiologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo
18.
PLoS One ; 19(5): e0303373, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38728271

RESUMO

BACKGROUND: Candida represents a prevalent fungal infection, notable for its substantial implications on morbidity and mortality rates. In the landscape of prospective treatments, quinoxaline derivatives emerge as a category of compact compounds exhibiting notable potential in addressing infections. These derivatives showcase promising antimicrobial efficacy coupled with favorable pharmacokinetic and safety characteristics. AIMS: The central aim of this investigation was to examine the antifungal characteristics of 2-Chloro-3-hydrazinylquinoxaline against diverse strains of Candida and Aspergillus in vitro. Additionally, we endeavored to assess the in vivo efficacy of 2-Chloro-3-hydrazinylquinoxaline using a murine model for oral candidiasis induced by C. albicans cells ATCC 10231. RESULTS: 2-Chloro-3-hydrazinylquinoxaline demonstrated noteworthy effectiveness when tested against various reference strains of Candida species. It exhibited heightened efficacy, particularly against Candida krusei isolates. However, its performance against Candida albicans, Candida tropicalis, Candida glabrata, Candida parapsilosis, and Candida auris isolates exhibited variability. Notably, 2-Chloro-3-hydrazinylquinoxaline manifests variable efficacy against Aspergillus fumigatus, Aspergillus niger, Aspergillus terreus and Aspergillus flavus and no effect against Aspergillus brasiliensis. In a murine model, 2-Chloro-3-hydrazinylquinoxaline exhibited significant efficacy in combating the C. albicans cells ATCC 10231 strain, underscoring its potential as a viable treatment option. CONCLUSION: 2-Chloro-3-hydrazinylquinoxaline has demonstrated substantial potential in effectively addressing various Candida and Aspergillus species, showcasing dual attributes of antifungal and anti-inflammatory properties. However, to attain a more comprehensive understanding of its therapeutic capabilities, further investigations, incorporating additional tests and experiments, are imperative.


Assuntos
Antifúngicos , Candida , Testes de Sensibilidade Microbiana , Quinoxalinas , Antifúngicos/farmacologia , Antifúngicos/química , Quinoxalinas/farmacologia , Quinoxalinas/química , Animais , Candida/efeitos dos fármacos , Camundongos , Modelos Animais de Doenças , Candidíase/tratamento farmacológico , Candidíase/microbiologia , Feminino
19.
Eur Rev Med Pharmacol Sci ; 28(6): 2558-2568, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38567615

RESUMO

OBJECTIVE: The frequency and mortality of candidemia remain important. Non-albicans Candida species such as C. auris are increasing. PATIENTS AND METHODS: A retrospective review of adult patients diagnosed with bloodstream infection due to Candida species in the 17 months between July 1, 2020, and December 1, 2021, was performed. Yeast colonies grown in culture were identified by matrix-assisted laser desorption/ionization time-of-flight. Antifungal susceptibility tests of Candida strains were performed with Sensititre YeastOne (TREK Diagnostic Systems Inc., Westlake, Ohio) kits, and minimum inhibitory concentration values were evaluated according to the Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) clinical breakpoints. RESULTS: In total, 217 patients (mean age 64.9±15.7 years) were included. C. albicans was the most common fungus (detected in 82 patients; 37.8%), followed by C. parapsilosis (17.1%), C. glabrata (15.2%), C. tropicalis (15.2%), and C. auris (9%). Candidemia developed in 175 (81.4%) of the cases during their intensive care unit stay. Fluconazole (41.0%) and caspofungin (36.4%) were the two most frequently used antifungal agents in antifungal therapy. There were 114 (52.3%) deaths in the study group. Mortality rates were found to be lower in patients infected with C. parapsilosis or C. auris. Age and previous COVID-19 infection were other important risk factors. When the 217 Candida spp. were examined, resistance and intermediate susceptibility results were higher when EUCAST criteria were used. While the two methods were found to be fully compatible only for fluconazole, a partial agreement was also observed for voriconazole. CONCLUSIONS: As our study observed, the COVID-19 pandemic brought increasing numbers of immunosuppressed patients, widespread use of antibacterials, and central venous catheters, increasing the frequency and mortality of candidemia cases. All health institutions should be prepared for the diagnosis and treatment of candidemia. In addition, C. auris, the frequency of which has increased in recent years, is a new factor that should be considered in candidemia cases.


Assuntos
COVID-19 , Candidemia , Adulto , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candidemia/tratamento farmacológico , Candidemia/epidemiologia , Candidemia/microbiologia , Fluconazol/farmacologia , Fluconazol/uso terapêutico , Pandemias , Candida , Candida albicans , Candida glabrata , Testes de Sensibilidade Microbiana , Hospitais Urbanos
20.
J Vis Exp ; (205)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38619255

RESUMO

Facing a 40% mortality rate in candidemia patients, drug-resistant Candida and their petite mutants remain a major treatment challenge. Antimicrobial photodynamic therapy (aPDT) targets multiple fungal structures, unlike antibiotics/antifungals, potentially thwarting resistance. Traditional methods for inducing petite colonies rely on ethidium bromide or fluconazole, which can influence drug susceptibility and stress responses. This study investigated the application of green light (peak 520 nm) and rose bengal (RB) photosensitizer to combat a drug-resistant Candida glabrata isolate. The findings revealed that aPDT treatment significantly inhibited cell growth (≥99.9% reduction) and effectively induced petite colony formation, as evidenced by reduced size and loss of mitochondrial redox indicator staining. This study provides initial evidence that aPDT can induce petite colonies in a multidrug-resistant C. glabrata strain in vitro, offering a potentially transformative approach for combating resistant fungal infections.


Assuntos
Candida , Fotoquimioterapia , Humanos , Rosa Bengala/farmacologia , Candida glabrata , Fármacos Fotossensibilizantes/farmacologia
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