RESUMO

BACKGROUND: Candida auris has been identified by the World Health Organization as a critical pathogen due to its invasive nature, resistance to multiple drugs, and high mortality rates in hospital outbreaks. This fungus can persist on surfaces and human skin for extended periods, complicating infection control efforts. The need for effective disinfection strategies is urgent, as current disinfectants are often ineffective against C. auris biofilms. OBJECTIVE: The study aimed to identify potential disinfectants from a collection of 240 compounds in the Global Health Priority Box® that are effective against C. auris, particularly strains resistant to existing options. METHODS: The research employed a screening protocol using a fluconazole-resistant strain of C. auris (149/23). Antifungal activity was assessed using the microdilution method to determine Minimum Inhibitory Concentrations (MICs) and Minimum Fungicidal Concentrations (MFCs). Additional assays were conducted to evaluate biofilm inhibition, biofilm eradication, cell membrane integrity, nucleotide leakage, sorbitol protection assay, efflux pump inhibition, and hemolysis assay. RESULTS: Two compounds, Hydramethylnon (MMV1577471) and Flufenerim (MMV1794206), demonstrated significant inhibitory effects against C. auris. Hydramethylnon exhibited potent antifungal activity, inhibiting up to 93 % of fungal growth with an MFC of 16 µg/mL. Flufenerim inhibited up to 58 % of fungal growth, showing fungistatic action with an MFC greater than 4 µg/mL. Biofilm inhibition tests showed that both compounds significantly inhibited biofilm formation, with increased efficacy at higher concentrations. Both compounds showed eradication rates in both stages. Furthermore, Hydramethylnon and Flufenerim did not affect cell membrane integrity or nucleotide leakage, suggesting a mode of action not reliant on disrupting these cellular components. The sorbitol protection assay revealed that neither compound caused cell wall damage. In the efflux pump inhibition assay, Hydramethylnon did not activate efflux pumps, while Flufenerim activated efflux pumps, reducing its effectiveness. Hemocompatibility assay showed safety. CONCLUSION: The study highlights Hydramethylnon and Flufenerim as promising candidates for further development as disinfectants, offering potential solutions to the urgent need for effective disinfection agents against C. auris. The findings underscore the value of screening compound collections to identify novel antifungal agents and understand their mechanisms of action, thereby contributing to the advancement of new disinfection strategies in healthcare settings.

Assuntos

Antifúngicos , Biofilmes , Candida auris , Desinfetantes , Testes de Sensibilidade Microbiana , Biofilmes/efeitos dos fármacos , Antifúngicos/farmacologia , Desinfetantes/farmacologia , Candida auris/efeitos dos fármacos , Humanos , Farmacorresistência Fúngica Múltipla , Fluconazol/farmacologia , Candidíase/microbiologia , Candidíase/prevenção & controle , Saúde Global

RESUMO

This study investigates the presence of mycoviruses in Antarctic fungi and elucidates their evolutionary relationships. To achieve this, we aligned mycoviral gene sequences with genomes of previously sequenced Antarctic endophytic fungi, made available by our research group and accessible via Joint Genome Institute. Our findings reveal that the most prevalent genetic regions in all endophytic fungi are homologous to Partitiviruses, Baculoviridae, and Phycodnaviridae. These regions display evidence of positive selection pressure, suggesting genetic diversity and the accumulation of nonsynonymous mutations. This phenomenon implies a crucial role for these regions in the adaptation and survival of these fungi in the challenging Antarctic ecosystems. The presence of mycoviruses in Antarctic endophytic fungi may indicate shared survival strategies between the virus and its host, shedding light on their evolutionary dynamics. This study underscores the significance of exploring mycoviruses within endophytic fungi and their contributions to genetic diversity. Future research avenues could delve into the functional implications of these conserved mycoviral genetic regions in Antarctic endophytic fungi, providing a comprehensive understanding of this intriguing association and genomic retention of viral region in fungi.

Assuntos

Briófitas , Endófitos , Micovírus , Variação Genética , Genoma Viral , Filogenia , Regiões Antárticas , Micovírus/genética , Micovírus/isolamento & purificação , Micovírus/classificação , Genoma Viral/genética , Endófitos/genética , Endófitos/isolamento & purificação , Endófitos/virologia , Endófitos/classificação , Briófitas/microbiologia , Briófitas/virologia , Fungos/genética , Fungos/virologia , Fungos/isolamento & purificação , Fungos/classificação , Genômica , Evolução Molecular , Seleção Genética

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Candida auris poses a severe global health threat, with many strains resistant to antifungal treatments, complicating therapy. Exploring natural compounds alongside conventional drugs offers promising therapeutic avenues. The antifungal potential of the ethanolic extract from Caryocar brasiliense (Cb-EE), a plant native to the Brazilian cerrado and renowned for its medicinal properties, was investigated against C. auris. AIM OF THE STUDY: The study examined the chemical composition, antifungal activity, mechanisms of action, and in vivo effects of Cb-EE. MATERIALS AND METHODS: Leaves of C. brasiliense were processed to extract ethanolic extract, which was evaluated for phenolic compounds, flavonoids, and tannins. The antifungal capacity was determined through broth microdilution and checkerboard methods, assessing interaction with conventional antifungals. RESULTS: Cb-EE demonstrated fungistatic activity against various Candida species and Cryptococcus neoformans. Synergy with fluconazole and additive effects with other drugs were observed. Cb-EE inhibited C. auris growth, with the combination of fluconazole extending inhibition. Mechanistic studies revealed interference with fungal membranes, confirmed by sorbitol protection assays, cellular permeability tests, and scanning electron microscopy (SEM). Hemocompatibility and in vivo toxicity tests on Tenebrio molitor showed safety. CONCLUSION: Cb-EE, alone or in combination with fluconazole, effectively treated C. auris infections in vitro and in vivo, suggesting its prospective role as an antifungal agent against this emerging pathogen.

Assuntos

Antifúngicos , Farmacorresistência Fúngica Múltipla , Testes de Sensibilidade Microbiana , Extratos Vegetais , Folhas de Planta , Antifúngicos/farmacologia , Antifúngicos/isolamento & purificação , Animais , Extratos Vegetais/farmacologia , Folhas de Planta/química , Candida auris/efeitos dos fármacos , Candida auris/isolamento & purificação , Fluconazol/farmacologia , Tenebrio , Sinergismo Farmacológico , Brasil , Candida/efeitos dos fármacos , Cryptococcus neoformans/efeitos dos fármacos

RESUMO

BACKGROUND: Autosomal recessive deficiency in the caspase recruitment domain-containing protein 9 (CARD9) is a congenital immunological condition that leads to susceptibility to mucocutaneous and invasive fungal infections. There is growing incidence of fungal infections in patients with CARD9 deficiency, a phenomenon that is increasingly recognised. OBJECTIVES: This study aimed to assess the frequency, geographic distribution and nature of mutations in patients with CARD9 deficiency, based on published papers in the literature until March 2023. METHODS: We swiftly conducted a study to pinpoint every documented instance of fungal infections arising from CARD9 deficiency. We selected case reports from the databases of PubMed, Embase, Scopus and Google Scholar spanning the period from October 2009 to March 2023. RESULTS: We analysed 90 cases of fungal infections and identified 32 mutations in the CARD9 gene. Notably, the homozygous (HMZ) p.Q295X (c.883C > T) mutation was associated with an increased risk of candidiasis. In contrast, the HMZ p.Q289X (c.865C > T) mutation is linked to a higher risk of dermatophytosis. We observed differences in the geographical distribution of these mutations. The primary mutations found in African patients differ from those in Asian patients. Specifically, Asian patients exhibit a broader spectrum of CARD9 mutations than African patients. CONCLUSIONS: The diversity of mutations observed in the 90 cases revealed 32 distinct variations, emphasising the unique genetic alterations in the CARD9 gene associated with specific geographical areas and the corresponding prevalence of fungal infections.

Assuntos

Candidíase Mucocutânea Crônica , Candidíase , Infecções Fúngicas Invasivas , Humanos , Mutação , Infecções Fúngicas Invasivas/epidemiologia , Proteínas Adaptadoras de Sinalização CARD/genética

RESUMO

Burns can cause skin damage, facilitating the entry of fungi and other microorganisms into the body, leading to infections. Fusarium is a fungus capable of infecting individuals with burn injuries. Diagnosing and treating Fusarium infections in burn patients can be challenging due to the manifestation of nonspecific symptoms. This study aims to investigate case reports and case series from published literature describing Fusarium infection in burned patients, in order to assess treatment regimens, clinical outcomes, and make recommendations for future management. We conducted searches on Web of Science, PubMed, ScienceDirect, and Medline for all case reports and case series containing keywords 'Burn', 'Burns', 'Burned', 'Fusarium', or 'Fusariosis' in the title or abstract. All burn patients who developed Fusarium fungal infections between January 1974 and March 2023 were included in the study. Demographic and clinical data were analyzed retrospectivity. The final analysis incorporates 24 case reports encompassing a total of 87 burn patients with Fusarium infection. Patient ages ranged from one to 85 years, with the majority being male (53%). The median percentage of burn surface area was 78%, and the skin in the face, upper limbs, and lower limbs were the most commonly infected sites. Fungal infections appeared around 10 days after the burn injury on average. The majority of the patients were identified through culture or histopathology. The Fusarium dimerum species complex, which was found in nine patients, was the most frequently identified Fusarium species complex. Amphotericin B was the most preferred treatment drug, followed by voriconazole, and 62% of patients underwent debridement. In our study, 23 patients (37%) died from fungal infections. Implementing early and effective treatment protocols targeting Fusarium spp. in burn treatment units can significantly reduce mortality rates. It is critical to enhance the understanding of fusariosis epidemiology and emphasize the importance of maintaining a high clinical suspicion for this condition in burn patients.

Assuntos

Antifúngicos , Queimaduras , Fusariose , Fusarium , Humanos , Fusariose/microbiologia , Fusariose/tratamento farmacológico , Queimaduras/complicações , Queimaduras/microbiologia , Antifúngicos/uso terapêutico , Fusarium/isolamento & purificação , Masculino , Adulto , Pessoa de Meia-Idade , Feminino , Idoso , Adulto Jovem , Idoso de 80 Anos ou mais , Adolescente , Criança , Pré-Escolar , Lactente

RESUMO

Antarctica is one of the most inhospitable continents on the planet, with lichens and mosses being the most common terrestrial organisms in ice-free areas. Antarctica is represented by only two species of Angiosperms, Deschampsia antarctica Desv. (Poaceae) and Colobanthus quitensis (Kunth) Bartl. (Caryophyllaceae). In this study, we characterized fungi isolated from the fresh leaves of this grass species. The fungi were isolated from four individual plants from Half Moon Island (246 leaf fragments investigated), and seven from King George Island-Keller Peninsula (with 111 leaf fragments investigated) Antarctica. Neoascochyta paspali, Septoriella elongata, Pyrenophora cf. chaetomioides and Alternaria sp. were associated with the plant and identified through analysis of the sequences of the internal transcribed spacer region (ITS) of the rDNA and nuclear ribosomal large subunit rRNA gene (LSU) as well as through macro and micro-morphological characteristics. The isolates showed higher growth rate ranging from 10 to 20 °C. An interesting result was that the aforementioned fungi are already recognized as both plant pathogens and endophytic fungi. The results demonstrate that D. antarctica is an interesting fungal source. Those species might provide important information about the relationship on the endemic Antarctic biota.