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1.
New Microbiol ; 47(2): 152-156, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39023524

RESUMO

Herein, we aimed to investigate the antifungal susceptibility pattern of Candida auris clinical strains in our setting Bahrain Oncology Center-King Hamad University Hospital-Bahrain. C. auris strains isolated from different clinical specimens in the Microbiology Laboratory from October-2021 to November-2022 were evaluated. Species-level identification of fungi was performed by MALDI-TOF (Bruker, Germany). Minimum inhibitory concentration (MIC) was determined either by E-test strips or by MICRONAUT MIC system based on CDC guidelines for C. auris antifungal interpretation. Fluconazole, amphotericin-B, voriconazole, and caspofungin susceptibility data of the clinical strains were analyzed. A total of 40 clinical isolates were included: 25% were blood culture isolates, 65% were urinary, and 10% were soft tissue isolates. Only 29 strains could be tested for amphotericin-B and 32 for voriconazole. Overall resistance pattern was as follows: 100% resistance to fluconazole, 2.5% resistance to caspofungin, and 0% resistance to amphotericin b. Median voriconazole MIC was 0.015 ug/ml (min 0.08, max= 0.064 ug/ml). We had no fluconazole-sensitive strain and only one caspofungin-resistant strain. A single isolate (2.5%), which was associated with candidemia, demonstrated resistance to two antifungal agents: fluconazole and caspofungin. No triple or quadruple drug resistant strain existed.


Assuntos
Antifúngicos , Candida auris , Candidíase , Farmacorresistência Fúngica , Hospitais Universitários , Testes de Sensibilidade Microbiana , Antifúngicos/farmacologia , Humanos , Candidíase/microbiologia , Candida auris/efeitos dos fármacos , Feminino , Masculino , Adulto , Voriconazol/farmacologia , Pessoa de Meia-Idade , Centros de Atenção Terciária , Atenção Terciária à Saúde , Caspofungina/farmacologia , Candida/efeitos dos fármacos , Candida/isolamento & purificação
2.
Mycoses ; 67(7): e13765, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38988310

RESUMO

BACKGROUND: Candida auris, a multidrug-resistant fungal pathogen, has received considerable attention owing to its recent surge, especially in South America, which coincides with the ongoing global COVID-19 pandemic. Understanding the clinical and microbiological characteristics of outbreaks is crucial for their effective management and control. OBJECTIVE: This retrospective observational study aimed to characterize a C. auris outbreak at a Peruvian referral hospital between January 2021 and July 2023. METHODS: Data were collected from hospitalized patients with positive C. auris culture results. Microbiological data and antifungal susceptibility test results were analysed. Additionally, infection prevention and control measures have been described. Statistical analysis was used to compare the characteristics between the infected and colonized patients. RESULTS: Thirty-three patients were identified, mostly male (66.7%), with a median age of 53 years. Among them, 18 (54.5%) were colonized, and 15 (45.5%) were infected. Fungemia was the predominant presentation (80%), with notable cases of fungemia in tuberculosis patients with long-stay devices for parenteral anti-tuberculosis therapy. Seventy-five percent of the isolates exhibited fluconazole resistance. Echinocandins were the primary treatment, preventing fungemia recurrence within 30 days. Infected patients had significantly longer hospital stays than colonized patients (100 vs. 45 days; p = .023). Hospital mortality rates were 46.7% and 25% in the infected and fungemia patients, respectively. Simultaneous outbreaks of multidrug-resistant bacteria were documented. CONCLUSIONS: This study underscores the severity of a C. auris outbreak at a referral hospital in Peru, highlighting its significant impact on patient outcomes and healthcare resources. The high prevalence of fluconazole-resistant isolates, leading to prolonged hospital stay and high mortality rates, particularly in cases of fungemia, underscores the critical need for effective infection prevention and control strategies.


Assuntos
Antifúngicos , Candida auris , Candidíase , Surtos de Doenças , Humanos , Peru/epidemiologia , Pessoa de Meia-Idade , Masculino , Feminino , Estudos Retrospectivos , Adulto , Candidíase/epidemiologia , Candidíase/microbiologia , Antifúngicos/uso terapêutico , Antifúngicos/farmacologia , Idoso , Candida auris/efeitos dos fármacos , COVID-19/epidemiologia , Testes de Sensibilidade Microbiana , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Candida/efeitos dos fármacos , Candida/isolamento & purificação , Candida/classificação , Encaminhamento e Consulta
3.
Molecules ; 29(13)2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38998972

RESUMO

Heterocyclic compounds, particularly those containing azole rings, have shown extensive biological activity, including anticancer, antibacterial, and antifungal properties. Among these, the imidazole ring stands out due to its diverse therapeutic potential. In the presented study, we designed and synthesized a series of imidazole derivatives to identify compounds with high biological potential. We focused on two groups: thiosemicarbazide derivatives and hydrazone derivatives. We synthesized these compounds using conventional methods and confirmed their structures via nuclear magnetic resonance spectroscopy (NMR), MS, and elemental analysis, and then assessed their antibacterial and antifungal activities in vitro using the broth microdilution method against Gram-positive and Gram-negative bacteria, as well as Candida spp. strains. Our results showed that thiosemicarbazide derivatives exhibited varied activity against Gram-positive bacteria, with MIC values ranging from 31.25 to 1000 µg/mL. The hydrazone derivatives, however, did not display significant antibacterial activity. These findings suggest that structural modifications can significantly influence the antimicrobial efficacy of imidazole derivatives, highlighting the potential of thiosemicarbazide derivatives as promising candidates for further development in antibacterial therapies. Additionally, the cytotoxic activity against four cancer cell lines was evaluated. Two derivatives of hydrazide-hydrazone showed moderate anticancer activity.


Assuntos
Antibacterianos , Antifúngicos , Antineoplásicos , Bactérias Gram-Positivas , Testes de Sensibilidade Microbiana , Humanos , Antibacterianos/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Antifúngicos/farmacologia , Antifúngicos/síntese química , Antifúngicos/química , Bactérias Gram-Positivas/efeitos dos fármacos , Nitroimidazóis/farmacologia , Nitroimidazóis/química , Nitroimidazóis/síntese química , Linhagem Celular Tumoral , Bactérias Gram-Negativas/efeitos dos fármacos , Relação Estrutura-Atividade , Semicarbazidas/química , Semicarbazidas/farmacologia , Semicarbazidas/síntese química , Hidrazonas/química , Hidrazonas/farmacologia , Hidrazonas/síntese química , Candida/efeitos dos fármacos , Estrutura Molecular
4.
Curr Microbiol ; 81(9): 271, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39012492

RESUMO

Probiotics and prebiotics have been considered as alternative approaches for promoting health. This study aimed to investigate the anticandidal potential of various probiotic Lactobacillus strains and their cell-free supernatants (CFSs). The study assessed the impact of inulin and some fruits as prebiotics on the growth of selected probiotic strains in relation to their anticandidal activity, production of short-chain fatty acids, total phenolic content, and antioxidant activity. Results revealed variations in anticandidal activity based on the specific strains and forms of probiotics used. Non-adjusted CFSs were the most effective against Candida strains, followed by probiotic cells and adjusted CFSs (pH 7). Lacticaseibacillus rhamnosus SD4, L. rhamnosus SD11 and L. rhamnosus GG displayed the strongest anticandidal activity. Non-adjusted CFSs from L. rhamnosus SD11, L. rhamnosus SD4 and L. paracasei SD1 exhibited notable anticandidal effects. The adjusted CFSs of L. rhamnosus SD11 showed the highest anticandidal activity against all non-albicans Candida (NAC) strains, whereas the others were ineffective. Supplementation of L. rhamnosus SD11 with prebiotics, particularly 2% (w/v) mangosteen, exhibited positive results in promoting probiotic growth, short-chain fatty acids production, total phenolic contents, and antioxidant activity, and the subsequent enhancing anticandidal activity against both C. albicans and NAC strains compared to conditions without prebiotics. In conclusion, both live cells and CFSs of tested strains, particularly L. rhamnosus SD11, exhibited the best anticandidal activity. Prebiotics supplementation, especially mangosteen, enhanced probiotic growth and beneficial metabolites against Candida growth. These finding suggested that probiotics and prebiotic supplementation may be an effective alternative treatment for Candida infections.


Assuntos
Lactobacillus , Prebióticos , Probióticos , Probióticos/farmacologia , Lactobacillus/metabolismo , Candida/efeitos dos fármacos , Candida/crescimento & desenvolvimento , Antioxidantes/farmacologia , Inulina/farmacologia , Antifúngicos/farmacologia , Ácidos Graxos Voláteis/metabolismo , Lacticaseibacillus rhamnosus/metabolismo , Fenóis/farmacologia
5.
J Med Microbiol ; 73(7)2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38979984

RESUMO

Introduction. The development of new antifungal drugs has become a global priority, given the increasing cases of fungal diseases together with the rising resistance to available antifungal drugs. In this scenario, drug repositioning has emerged as an alternative for such development, with advantages such as reduced research time and costs.Gap statement. Propafenone is an antiarrhythmic drug whose antifungal activity is poorly described, being a good candidate for further study.Aim. This study aims to evaluate propafenone activity against different species of Candida spp. to evaluate its combination with standard antifungals, as well as its possible action mechanism.Methodology. To this end, we carried out tests against strains of Candida albicans, Candida auris, Candida parapsilosis, Candida tropicalis, Candida glabrata and Candida krusei based on the evaluation of the MIC, minimum fungicidal concentration and tolerance level, along with checkerboard and flow cytometry tests with clinical strains and cell structure analysis by scanning electron microscopy (SEM).Results. The results showed that propafenone has a 50% MIC ranging from 32 to 256 µg ml-1, with fungicidal activity and positive interactions with itraconazole in 83.3% of the strains evaluated. The effects of the treatments observed by SEM were extensive damage to the cell structure, while flow cytometry revealed the apoptotic potential of propafenone against Candida spp.Conclusion. Taken together, these results indicate that propafenone has the potential for repositioning as an antifungal drug.


Assuntos
Antifúngicos , Candida , Testes de Sensibilidade Microbiana , Propafenona , Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Candida/crescimento & desenvolvimento , Propafenona/farmacologia , Humanos , Itraconazol/farmacologia , Sinergismo Farmacológico , Farmacorresistência Fúngica/efeitos dos fármacos , Candidíase/microbiologia , Candidíase/tratamento farmacológico , Reposicionamento de Medicamentos
6.
J Indian Soc Pedod Prev Dent ; 42(2): 83-90, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38957904

RESUMO

BACKGROUND AND OBJECTIVES: Mucopolysaccharidosis (MPS) is a group of lysosomal storage disorders that cause the deposition of polysaccharides in cells. This causes systemic and oral manifestations, which can be observed clinically and radiographically. The present study aimed to assess dental caries, the effect of salivary pH, and the change of microflora on teeth in patients diagnosed with MPS. MATERIALS AND METHODS: The study included children affected with mucopolysaccharidosis (n = 50) and healthy children (n = 50) in the control group between 3 and 15 years of age. The pH of saliva and decayed, missing, and filled teeth/decayed extracted and filled teeth index were noted and recorded. For the microbial analysis, saliva was inoculated into blood agar, MacConkey agar, Candida CHROMagar, and Mitis Salivarius agar, then inspected for colony-forming units, which were counted and recorded based on the colony characteristics and gram staining. STATISTICAL ANALYSIS: Intergroup comparison of the test parameters was done using the Mann-Whitney test. P < 0.05 was considered statistically significant. RESULTS: The results showed significantly higher total microbial load (P = 0.00008), streptococcus viridans species (P = 0.00001), and Candida species (P = 0.0038) in the study group. The caries incidence was also higher in the study group for both primary (P = 0.0096) and permanent dentition (P = 0.0251), and salivary pH was more acidic (P = 0.00001) in the patients diagnosed with MPS. INTERPRETATION AND CONCLUSION: Patients diagnosed with MPS have a higher microbial load, more acidic saliva, and subsequently, a higher caries incidence than normal healthy children. Hence, regular dental evaluation, prevention, and treatment must be integrated into their health-care regimen.


Assuntos
Cárie Dentária , Mucopolissacaridoses , Saliva , Humanos , Saliva/microbiologia , Criança , Cárie Dentária/microbiologia , Cárie Dentária/diagnóstico , Adolescente , Mucopolissacaridoses/complicações , Mucopolissacaridoses/diagnóstico , Pré-Escolar , Feminino , Masculino , Concentração de Íons de Hidrogênio , Índice CPO , Candida/isolamento & purificação , Estudos de Casos e Controles
7.
Euro Surveill ; 29(29)2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39027938

RESUMO

BackgroundThe COVID-19 pandemic and the emergence of Candida auris have changed the epidemiological landscape of candidaemia worldwide.AimWe compared the epidemiological trends of candidaemia in a Greek tertiary academic hospital before (2009-2018) and during the early COVID-19 (2020-2021) and late COVID-19/early post-pandemic (2022-2023) era.MethodsIncidence rates, species distribution, antifungal susceptibility profile and antifungal consumption were recorded, and one-way ANOVA or Fisher's exact test performed. Species were identified by MALDI-ToF MS, and in vitro susceptibility determined with CLSI M27-Ed4 for C. auris and the EUCAST-E.DEF 7.3.2 for other Candida spp.ResultsIn total, 370 candidaemia episodes were recorded during the COVID-19 pandemic. Infection incidence (2.0 episodes/10,000 hospital bed days before, 3.9 during the early and 5.1 during the late COVID-19 era, p < 0.0001), C. auris (0%, 9% and 33%, p < 0.0001) and fluconazole-resistant C. parapsilosis species complex (SC) (20%, 24% and 33%, p = 0.06) infections increased over time, with the latter not associated with increase in fluconazole/voriconazole consumption. A significant increase over time was observed in fluconazole-resistant isolates regardless of species (8%, 17% and 41%, p < 0.0001). Resistance to amphotericin B or echinocandins was not recorded, with the exception of a single pan-echinocandin-resistant C. auris strain.ConclusionCandidaemia incidence nearly tripled during the COVID-19 era, with C. auris among the major causative agents and increasing fluconazole resistance in C. parapsilosis SC. Almost half of Candida isolates were fluconazole-resistant, underscoring the need for increased awareness and strict implementation of infection control measures.


Assuntos
Antifúngicos , COVID-19 , Candidemia , Farmacorresistência Fúngica , Fluconazol , Testes de Sensibilidade Microbiana , SARS-CoV-2 , Centros de Atenção Terciária , Humanos , Candidemia/epidemiologia , Candidemia/tratamento farmacológico , Candidemia/microbiologia , Grécia/epidemiologia , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , COVID-19/epidemiologia , Centros de Atenção Terciária/estatística & dados numéricos , Fluconazol/farmacologia , Fluconazol/uso terapêutico , Candida parapsilosis/efeitos dos fármacos , Candida parapsilosis/isolamento & purificação , Incidência , Candida auris/efeitos dos fármacos , Candida/efeitos dos fármacos , Candida/isolamento & purificação , Adulto , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Pandemias , Candidíase/epidemiologia , Candidíase/tratamento farmacológico , Candidíase/microbiologia
8.
Eur J Med Chem ; 275: 116637, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-38959728

RESUMO

Life-threatening invasive fungal infections pose a serious threat to human health. A series of novel triazole derivatives bearing a pyrazole-methoxyl moiety were designed and synthesized in an effort to obtain antifungals with potent, broad-spectrum activity that are less susceptible to resistance. Most of these compounds exhibited moderate to excellent in vitro antifungal activities against Candida albicans SC5314 and 10,231, Cryptococcus neoformans 32,609, Candida glabrata 537 and Candida parapsilosis 22,019 with minimum inhibitory concentration (MIC) values of ≤0.125 µg/mL to 0.5 µg/mL. Use of recombinant Saccharomyces cerevisiae strains showed compounds 7 and 10 overcame the overexpression and resistant-related mutations in ERG11 of S. cerevisae and several pathogenic Candida spp. Despite being substrates of the C. albicans and Candida auris Cdr1 drug efflux pumps, compounds 7 and 10 showed moderate potency against five fluconazole (FCZ)-resistant fungi with MIC values from 2.0 µg/mL to 16.0 µg/mL. Growth kinetics confirmed compounds 7 and 10 had much stronger fungistatic activity than FCZ. For C. albicans, compounds 7 and 10 inhibited the yeast-to-hyphae transition, biofilm formation and destroyed mature biofilm more effectively than FCZ. Preliminary mechanism of action studies showed compounds 7 and 10 blocked the ergosterol biosynthesis pathway at Erg11, ultimately leading to cell membrane disruption. Further investigation of these novel triazole derivatives is also warranted by their predicted ADMET properties and low cytotoxicity.


Assuntos
Antifúngicos , Candida , Testes de Sensibilidade Microbiana , Pirazóis , Triazóis , Antifúngicos/farmacologia , Antifúngicos/síntese química , Antifúngicos/química , Triazóis/química , Triazóis/farmacologia , Triazóis/síntese química , Pirazóis/química , Pirazóis/farmacologia , Pirazóis/síntese química , Relação Estrutura-Atividade , Candida/efeitos dos fármacos , Estrutura Molecular , Relação Dose-Resposta a Droga , Cryptococcus neoformans/efeitos dos fármacos , Humanos , Farmacorresistência Fúngica/efeitos dos fármacos , Saccharomyces cerevisiae/efeitos dos fármacos , Candida albicans/efeitos dos fármacos
9.
Biochemistry ; 63(14): 1824-1836, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-38968244

RESUMO

Faced with the emergence of multiresistant microorganisms that affect human health, microbial agents have become a serious global threat, affecting human health and plant crops. Antimicrobial peptides have attracted significant attention in research for the development of new microbial control agents. This work's goal was the structural characterization and analysis of antifungal activity of chitin-binding peptides from Capsicum baccatum and Capsicum frutescens seeds on the growth of Candida and Fusarium species. Proteins were initially submitted to extraction in phosphate buffer pH 5.4 and subjected to chitin column chromatography. Posteriorly, two fractions were obtained for each species, Cb-F1 and Cf-F1 and Cb-F2 and Cf-F2, respectively. The Cb-F1 (C. baccatum) and Cf-F1 (C. frutescens) fractions did not bind to the chitin column. The electrophoresis results obtained after chromatography showed two major protein bands between 3.4 and 14.2 kDa for Cb-F2. For Cf-F2, three major bands were identified between 6.5 and 14.2 kDa. One band from each species was subjected to mass spectrometry, and both bands showed similarity to nonspecific lipid transfer protein. Candida albicans and Candida tropicalis had their growth inhibited by Cb-F2. Cf-F2 inhibited the development of C. albicans but did not inhibit the growth of C. tropicalis. Both fractions were unable to inhibit the growth of Fusarium species. The toxicity of the fractions was tested in vivo on Galleria mellonella larvae, and both showed a low toxicity rate at high concentrations. As a result, the fractions have enormous promise for the creation of novel antifungal compounds.


Assuntos
Antifúngicos , Candida , Quitina , Fusarium , Simulação de Acoplamento Molecular , Antifúngicos/farmacologia , Antifúngicos/química , Antifúngicos/metabolismo , Quitina/química , Quitina/metabolismo , Fusarium/efeitos dos fármacos , Candida/efeitos dos fármacos , Proteínas de Transporte/química , Proteínas de Transporte/metabolismo , Animais , Capsicum/química , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Proteínas de Plantas/farmacologia , Testes de Sensibilidade Microbiana , Ligação Proteica , Conformação Proteica
10.
J Biosci Bioeng ; 138(2): 111-117, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38824112

RESUMO

The synthesis of carbocyclic-ddA, a potent antiviral agent against hepatitis B, relies significantly on (1R,3R)-3-hydroxycyclopentanemethanol as a key intermediate. To effectively produce this intermediate, our study employed a chemoenzymatic approach. The selection of appropriate biocatalysts was based on substrate similarity, leading us to adopt the CrS enoate reductase derived from Thermus scotoductus SA-01. Additionally, we developed an enzymatic system for NADH regeneration, utilising formate dehydrogenase from Candida boidinii. This system facilitated the efficient catalysis of (S)-4-(hydroxymethyl)cyclopent-2-enone, resulting in the formation of (3R)-3-(hydroxymethyl) cyclopentanone. Furthermore, we successfully cloned, expressed, purified, and characterized the CrS enzyme in Escherichia coli. Optimal reaction conditions were determined, revealing that the highest activity occurred at 45 °C and pH 8.0. By employing 5 mM (S)-4-(hydroxymethyl)cyclopent-2-enone, 0.05 mM FMN, 0.2 mM NADH, 10 µM CrS, 40 µM formic acid dehydrogenase, and 40 mM sodium formate, complete conversion was achieved within 45 min at 35 °C and pH 7.0. Subsequently, (1R,3R)-3-hydroxycyclopentanemethanol was obtained through a simple three-step chemical conversion process. This study not only presents an effective method for synthesizing the crucial intermediate but also highlights the importance of biocatalysts and enzymatic systems in chemoenzymatic synthesis approaches.


Assuntos
Ciclopentanos , Escherichia coli , Ciclopentanos/metabolismo , Escherichia coli/metabolismo , Escherichia coli/genética , Candida/enzimologia , Formiato Desidrogenases/metabolismo , Formiato Desidrogenases/genética , Antivirais/metabolismo , Antivirais/síntese química , NAD/metabolismo , Biocatálise , Oxirredutases/metabolismo , Clonagem Molecular
11.
J Clin Microbiol ; 62(7): e0052524, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-38888304

RESUMO

Candida auris is a multidrug-resistant fungal pathogen with a propensity to colonize humans and persist on environmental surfaces. C. auris invasive fungal disease is being increasingly identified in acute and long-term care settings. We have developed a prototype cartridge-based C. auris surveillance assay (CaurisSurV cartridge; "research use only") that includes integrated sample processing and nucleic acid amplification to detect C. auris from surveillance skin swabs in the GeneXpert instrument and is designed for point-of-care use. The assay limit of detection (LoD) in the skin swab matrix was 10.5 and 14.8 CFU/mL for non-aggregative (AR0388) and aggregative (AR0382) strains of C. auris, respectively. All five known clades of C. auris were detected at 2-3-5× (31.5-52.5 CFU/mL) the LoD. The assay was validated using a total of 85 clinical swab samples banked at two different institutions (University of California Los Angeles, CA and Wadsworth Center, NY). Compared to culture, sensitivity was 96.8% (30/31) and 100% (10/10) in the UCLA and Wadsworth cohorts, respectively, providing a combined sensitivity of 97.5% (40/41), and compared to PCR, the combined sensitivity was 92% (46/50). Specificity was 100% with both clinical (C. auris negative matrix, N = 31) and analytical (non-C. auris strains, N = 32) samples. An additional blinded study with N = 60 samples from Wadsworth Center, NY yielded 97% (29/30) sensitivity and 100% (28/28) specificity. We have developed a completely integrated, sensitive, specific, and 58-min prototype test, which can be used for routine surveillance of C. auris and might help prevent colonization and outbreaks in acute and chronic healthcare settings. IMPORTANCE: This study has the potential to offer a better solution to healthcare providers at hospitals and long-term care facilities in their ongoing efforts for effective and timely control of Candida auris infection and hence quicker response for any potential future outbreaks.


Assuntos
Candida auris , Candidíase , Sensibilidade e Especificidade , Humanos , Candidíase/diagnóstico , Candidíase/microbiologia , Candida auris/genética , Controle de Infecções/métodos , Monitoramento Epidemiológico , Pele/microbiologia , Limite de Detecção , Sistemas Automatizados de Assistência Junto ao Leito , Técnicas de Amplificação de Ácido Nucleico/métodos , Técnicas de Diagnóstico Molecular/métodos , Candida/isolamento & purificação , Candida/genética , Candida/classificação
12.
BMC Biotechnol ; 24(1): 43, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38909197

RESUMO

Fungal diseases are often linked to poverty, which is associated with poor hygiene and sanitation conditions that have been severely worsened by the COVID-19 pandemic. Moreover, COVID-19 patients are treated with Dexamethasone, a corticosteroid that promotes an immunosuppressive profile, making patients more susceptible to opportunistic fungal infections, such as those caused by Candida species. In this study, we analyzed the prevalence of Candida yeasts in wastewater samples collected to track viral genetic material during the COVID-19 pandemic and identified the yeasts using polyphasic taxonomy. Furthermore, we investigated the production of biofilm and hydrolytic enzymes, which are known virulence factors. Our findings revealed that all Candida species could form biofilms and exhibited moderate hydrolytic enzyme activity. We also proposed a workflow for monitoring wastewater using Colony PCR instead of conventional PCR, as this technique is fast, cost-effective, and reliable. This approach enhances the accurate taxonomic identification of yeasts in environmental samples, contributing to environmental monitoring as part of the One Health approach, which preconizes the monitoring of possible emergent pathogenic microorganisms, including fungi.


Assuntos
COVID-19 , Candida , Águas Residuárias , Fluxo de Trabalho , Águas Residuárias/microbiologia , Águas Residuárias/virologia , Brasil/epidemiologia , Candida/isolamento & purificação , Candida/genética , Candida/classificação , COVID-19/epidemiologia , COVID-19/virologia , Humanos , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Biofilmes , Monitoramento Ambiental/métodos , Pandemias
13.
Sheng Wu Gong Cheng Xue Bao ; 40(6): 1882-1894, 2024 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-38914498

RESUMO

1,4-cyclohexanedimethylamine (1,4-BAC) is an important monomer for bio-based materials, it finds wide applications in various fields including organic synthesis, medicine, chemical industry, and materials. At present, its synthesis primarily relies on chemical method, which suffer from issues such as expensive metal catalyst, harsh reaction conditions, and safety risks. Therefore, it is necessary to explore greener alternatives for its synthesis. In this study, a two-bacterium three-enzyme cascade conversion pathway was successfully developed to convert 1,4-cyclohexanedicarboxaldehyde to 1,4-cyclohexanedimethylamine. This pathway used Escherichia coli derived aminotransferase (EcTA), Saccharomyces cerevisiae derived glutamate dehydrogenase (ScGlu-DH), and Candida boidinii derived formate dehydrogenase (CbFDH). Through structure-guided protein engineering, a beneficial mutant, EcTAF91Y, was obtained, exhibiting a 2.2-fold increase in specific activity and a 1.9-fold increase in kcat/Km compared to that of the wild type. By constructing recombinant strains and optimizing reaction conditions, it was found that under the optimal conditions, a substrate concentration of 40 g/L could produce (27.4±0.9) g/L of the product, corresponding to a molar conversion rate of 67.5%±2.1%.


Assuntos
Escherichia coli , Saccharomyces cerevisiae , Escherichia coli/metabolismo , Escherichia coli/genética , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/enzimologia , Transaminases/metabolismo , Transaminases/genética , Engenharia de Proteínas , Glutamato Desidrogenase/metabolismo , Glutamato Desidrogenase/genética , Formiato Desidrogenases/metabolismo , Formiato Desidrogenases/genética , Candida/enzimologia , Candida/metabolismo , Cicloexilaminas/metabolismo
14.
BMC Oral Health ; 24(1): 738, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38937749

RESUMO

BACKGROUND: The aim of this study was to evaluate the adhesion of Candida glabrata, Candida albicans, Candida krusei, Candida parapsilosis and Candida tropicalis yeasts to disk-shaped resin materials produced from resin which used in the production of surgical guide with 0, 45 and 90-degrees printing orientations by Liquid Crystal Display additive manufacturing technology. METHODS: Disk-shaped specimens were printed with surgical guide resin using the Liquid Crystal Display production technique in 3 printing orientations (0, 45 and 90-degrees). Surface roughness and contact angle values were evaluated. Real-Time PCR analysis was performed to evaluate Candida adhesion (C. glabrata, C. albicans, C. krusei, C. parapsilosis and C. tropicalis) Field emission scanning electron microscope (FESEM) images of the materials were obtained. RESULTS: Specimens oriented at 45-degrees demonstrated higher surface roughness (P < .05) and lower contact angle values than other groups. No significant difference was found in the adhesion of C. glabrata, C. albicans, and C. parapsilosis among specimens printed at 0, 45, and 90-degrees orientations (P > .05). A higher proportion of C. krusei and C. tropicalis was found in the specimens printed at orientation degrees of 45 = 90 < 0 with statistical significance. Analyzing the adhesion of all Candida species reveals no statistical disparity among the printing orientations. CONCLUSIONS: The surface roughness, contact angle, and adhesion of certain Candida species are affected by printing orientations. Hence, careful consideration of the printing orientation is crucial for fabricating products with desirable properties. In 45-degree production, roughness increases due to the layered production forming steps, whereas in 0-degree production, certain Candida species exhibit high adhesion due to the formation of porous structures. Consequently, considering these factors, it is advisable to opt for production at 90-degrees, while also considering other anticipated characteristics.


Assuntos
Candida , Microscopia Eletrônica de Varredura , Propriedades de Superfície , Candida glabrata , Candida tropicalis , Candida parapsilosis , Humanos , Candida albicans , Teste de Materiais , Adesão Celular , Reação em Cadeia da Polimerase em Tempo Real , Impressão Tridimensional , Resinas Sintéticas , Molhabilidade
15.
Mymensingh Med J ; 33(3): 671-676, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38944705

RESUMO

In Intensive Care Units (ICUs) infection represents the most frequent complication leading to high mortality. Particularly the incidence of fungal infections, especially due to Candida spp., has been increasing during the last years. Over last two decades there is predominance of Non albicans Candida (NAC) infection with increased isolation of novel species and decreased susceptibility. Early identification of Candida species and determination of antifungal susceptibility pattern is essential for effective management. Therefore, the study was conducted to isolate and identify Candida species from the blood samples of the patients suspected of candidemia and assess their antifungal susceptibility pattern. This cross-sectional, descriptive type of observational study was conducted in the Department of Microbiology, Mymensingh Medical College, Bangladesh from March 2021 to February 2022. Venous blood was collected from clinically suspected patients admitted at ICU, Neonatal Intensive Care Unit (NICU), Mymensingh Medical College Hospital, Bangladesh. Primary blood culture was performed by automated method followed by sub-culture in Saboraud's Dextrose Agar (SDA) and blood agar media. Candida species were recognized by phenotypic and genotypic methods. Antifungal susceptibility testing was done by disk diffusion and broth microdilution method (BMD). Out of 125 blood specimens collected, Candida species were isolated from 39(31.0%) blood samples of which NAC species were 35(89.0%) whereas C. albicans was only 4(10.2%). Eight (8) different Candida species were identified of which C. parapsilosis was predominant 16(41.0%). Rare and emerging drug resistant species of C. ciferrii 23.0%, C. auris 7.7%, C. rugosa 10.3%, C. lusitaniae 2.6% were also isolated. Candidemia was highest in neonate 33(84.61%) with male predominance 24(61.54%). Use of broad-spectrum antibiotics, prolonged hospital stay, pre-maturity and low birth weight (LBW) were found to be important risk factors. In candidemia the highest resistance was to Fluconazole-33% and lowest to Voriconazole-5%. The study showed that NAC species were more common with emergence of rare and multidrug resistant species.


Assuntos
Antifúngicos , Candida , Candidemia , Unidades de Terapia Intensiva , Testes de Sensibilidade Microbiana , Humanos , Bangladesh/epidemiologia , Candidemia/epidemiologia , Candidemia/microbiologia , Candidemia/tratamento farmacológico , Estudos Transversais , Feminino , Masculino , Candida/isolamento & purificação , Candida/efeitos dos fármacos , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Unidades de Terapia Intensiva/estatística & dados numéricos , Recém-Nascido , Adulto , Farmacorresistência Fúngica
16.
Environ Microbiol Rep ; 16(3): e13282, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38923398

RESUMO

The global landscape of Candida infections has seen a significant shift. Previously, Candida albicans was the predominant species. However, there has been an emergence of non-albicans Candida species, which are often less susceptible to antifungal treatment. Candida kefyr, in particular, has been increasingly associated with infections. This study aimed to investigate the profiles of enzymatic activity and biofilm formation in both clinical and non-clinical isolates of C. kefyr. A total of 66 C. kefyr isolates were analysed. The activities of proteinase and phospholipase were assessed using bovine serum albumin and egg yolk agar, respectively. Haemolysin, caseinolytic and esterase activities were evaluated using specific methods. Biofilm formation was investigated using crystal violet staining. The findings indicated that biofilm and proteinase activity were detected in 81.8% and 93.9% of all the isolates, respectively. Haemolysin activity was observed with the highest occurrence (95.5%) among normal microbiota isolates. Esterase activity was predominantly identified in dairy samples and was absent in hospital samples. Caseinase production was found with the highest occurrence (18.2%) in normal microbiota and hospital samples. Phospholipase activity was limited, found in only 3% of all the isolates. These findings reveal variations in enzyme activity between clinical and non-clinical C. kefyr isolates. This sheds light on their pathogenic potential and has implications for therapeutic strategies.


Assuntos
Biofilmes , Candida , Candidíase , Fosfolipases , Biofilmes/crescimento & desenvolvimento , Candida/isolamento & purificação , Candida/enzimologia , Candida/fisiologia , Candida/classificação , Humanos , Candidíase/microbiologia , Fosfolipases/metabolismo , Esterases/metabolismo , Proteínas Hemolisinas/metabolismo , Peptídeo Hidrolases/metabolismo , Microbiologia Ambiental
17.
Future Microbiol ; 19(7): 577-584, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38884219

RESUMO

Aim: The objective of this study was to evaluate the clinical and epidemiological aspects of Candida infections. Methods: The study relied on the analysis of electronic medical records. Results: Among 183 patients with positive fungal infections, 57 were from the community and 126 from hospitals. Females predominated in both groups (82.4% in the community, 54.7% in hospitals). Non-albicans Candida spp. accounted for 62.8% of cases. Antifungal therapy was prescribed for 67 patients, with a 55.6% mortality rate. Conclusion: The increasing prevalence of non-albicans Candida species highlights the need for better candidiasis monitoring and control, especially concerning antifungal use amidst rising antimicrobial resistance, particularly in empirical therapy scenarios.


Fungal infections, particularly those caused by a group of yeasts called Candida, are a major concern. This study looks at clinical laboratory and medical records. We found that certain species of Candida not previously associated with human disease are common. We also noted the inappropriate use of antifungal medication, highlighting the need for healthcare workers to carefully diagnose patients and make appropriate decisions when treating fungal infections.


Assuntos
Antifúngicos , Candida , Candidíase , Farmacorresistência Fúngica , Humanos , Antifúngicos/uso terapêutico , Antifúngicos/farmacologia , Feminino , Masculino , Candida/efeitos dos fármacos , Candida/isolamento & purificação , Pessoa de Meia-Idade , Candidíase/epidemiologia , Candidíase/tratamento farmacológico , Candidíase/microbiologia , Candidíase/mortalidade , Idoso , Adulto , Idoso de 80 Anos ou mais , Prevalência , Adulto Jovem , Adolescente , Criança , Estudos Retrospectivos , Pré-Escolar
18.
Food Chem ; 455: 139860, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-38823137

RESUMO

The current trend is the promotion of antioxidants that are beneficial for both health and the environment. Candida utilis have garnered considerable attention due to their commendable attributes such as non-toxicity and the ability to thrive in waste. Therefore, Candida utilis was used as raw material to isolate and identify new antioxidant peptides by employing methods such as ultrafiltration, DEAE Sepharose Fast Flow, and liquid chromatography-tandem mass spectrometry. The antioxidant mechanism of peptides was investigated by molecular docking. The properties of antioxidant peptides were evaluated using a variety of computational tools. This study resulted in the identification of two novel antioxidant peptides. According to the molecular docking results, the antioxidant mechanism of Candida utilis peptides operates by obstructing the entry to the myeloperoxidase activity cavity. The (-) CDOCKER energy of antioxidant peptides was 6.2 and 6.1 kcal/mol, respectively. Additionally, computer predictions indicated that antioxidant peptides exhibited non-toxicity and poor solubility.


Assuntos
Antioxidantes , Candida , Simulação de Acoplamento Molecular , Peptídeos , Antioxidantes/química , Antioxidantes/metabolismo , Candida/química , Candida/enzimologia , Peptídeos/química , Peptídeos/metabolismo , Proteínas Fúngicas/química , Proteínas Fúngicas/metabolismo , Espectrometria de Massas em Tandem
19.
Mycopathologia ; 189(4): 60, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38940953

RESUMO

INTRODUCTION: Candidemia, a bloodstream infection predominantly affecting critically ill patients, poses a significant global health threat especially with the emergence of non-albicans Candida species, including drug-resistant strains. In Brazil, limited access to advanced diagnostic tools and trained microbiologists hampers accurate identification of Candida species and susceptibility to antifungals testing hindering surveillance efforts. METHODS: We conducted a systematic review spanning publications from 2017 to 2023 addressing Candida species distribution and antifungal susceptibility among Brazilian patients with candidemia. RESULTS: Despite initially identifying 7075 records, only 16 met inclusion criteria providing accurate information of 2305 episodes of candidemia. The predominant species were C. albicans, C. parapsilosis, and C. tropicalis, followed by notable proportions of Nakaseomyces glabratus. Limited access to diagnostic tests was evident as only 5 out of 16 studies on candidemia were able to report antifungal susceptibility testing results. In vitro resistance to echinocandins was rare (only 6/396 isolates, 1,5%). In counterpart, fluconazole exhibited resistance rates ranging from 0 to 43%, with great heterogeneity among different studies and species of Candida considered. CONCLUSION: Our review underscores the critical need for enhanced surveillance and research efforts to address the evolving landscape of candidemia and antifungal resistance in Brazil. Despite some limitations, available data suggest that while resistance to echinocandins and amphotericin B remains rare, there is a growing concern regarding resistance to fluconazole among Candida species.


Assuntos
Antifúngicos , Candida , Candidemia , Farmacorresistência Fúngica , Testes de Sensibilidade Microbiana , Candidemia/epidemiologia , Candidemia/microbiologia , Candidemia/diagnóstico , Candidemia/tratamento farmacológico , Brasil/epidemiologia , Humanos , Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Candida/isolamento & purificação , Candida/classificação
20.
Front Cell Infect Microbiol ; 14: 1414618, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38903941

RESUMO

Candida species comprise a ubiquitous pathogenic fungal genus responsible for causing candidiasis. They are one of the primary causatives of several mucosal and systemic infections in humans and can survive in various environments. In this study, we investigated the antifungal, anti-biofilm, and anti-hyphal effects of six N-substituted phthalimides against three Candida species. Of the derivatives, N-butylphthalimide (NBP) was the most potent, with a minimum inhibitory concentration (MIC) of 100 µg/ml and which dose-dependently inhibited biofilm at sub-inhibitory concentrations (10-50 µg/ml) in both the fluconazole-resistant and fluconazole-sensitive Candida albicans and Candida parapsilosis. NBP also effectively inhibited biofilm formation in other pathogens including uropathogenic Escherichia coli, Staphylococcus epidermidis, Staphylococcus aureus, and Vibrio parahaemolyticus, along with the polymicrobial biofilms of S. epidermidis and C. albicans. NBP markedly inhibited the hyphal formation and cell aggregation of C. albicans and altered its colony morphology in a dose-dependent manner. Gene expression analysis showed that NBP significantly downregulated the expression of important hyphal- and biofilm-associated genes, i.e., ECE1, HWP1, and UME6, upon treatment. NBP also exhibited mild toxicity at concentrations ranging from 2 to 20 µg/ml in a nematode model. Therefore, this study suggests that NBP has anti-biofilm and antifungal potential against various Candida strains.


Assuntos
Antifúngicos , Biofilmes , Candida albicans , Hifas , Testes de Sensibilidade Microbiana , Ftalimidas , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Antifúngicos/farmacologia , Ftalimidas/farmacologia , Candida albicans/efeitos dos fármacos , Hifas/efeitos dos fármacos , Hifas/crescimento & desenvolvimento , Candida/efeitos dos fármacos , Candidíase/microbiologia , Candidíase/tratamento farmacológico , Animais , Humanos , Candida parapsilosis/efeitos dos fármacos , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Fluconazol/farmacologia
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