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1.
Chem Commun (Camb) ; 56(12): 1780-1783, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-31938791

RESUMO

Herein, we disclose the first set of unique selenium-containing SnAP reagents for the direct synthesis of C-substituted selenomorpholines and 1,4-selenazepanes, including their amino acid derivatives from commercially available aldehydes under mild conditions. These elusive N-unprotected heterocycles are not accessible by classical routes. Biological evaluation of these compounds revealed promising activities against clinically relevant fungal strains.


Assuntos
Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Candida parapsilosis/efeitos dos fármacos , Compostos de Selênio/farmacologia , Antifúngicos/síntese química , Antifúngicos/química , Relação Dose-Resposta a Droga , Testes de Sensibilidade Microbiana , Estrutura Molecular , Compostos de Selênio/síntese química , Compostos de Selênio/química , Relação Estrutura-Atividade
2.
Molecules ; 24(24)2019 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-31847159

RESUMO

In this study, we determined the antimicrobial activity of ten essential oils (EOs)-oregano, thyme, clove, arborvitae, cassia, lemongrass, melaleuca, eucalyptus, lavender, and clary sage-against drug-resistant microorganisms previously isolated from patients with skin infections. The essential oil compositions were determined using gas chromatography coupled to mass spectrometry (GC/MS). The assayed bacteria included Pseudomonas aeruginosa, Proteus vulgaris, Citrobacter koseri, and Klebsiella pneumoniae. Two drug-resistant yeasts (Candida albicans and Candida parapsilosis) were also involved in our survey. Oregano, thyme, cassia, lemongrass and arborvitae showed very strong antibacterial and antifungal activity against all tested strains. These results show that these essential oils may be effective in preventing the growth of the drug-resistant microorganisms responsible for wound infections. In this study, the genotoxic effects of tested essential oils on healthy human keratinocytes HaCaT were evaluated using the comet assay for the first time. These results revealed that none of the essential oils induced significant DNA damage in vitro after 24 h. Moreover, the treatment of HaCaT cells with essential oils increased the total antioxidant status (TAS) level. The obtained results indicate that EOs could be used as a potential source of safe and potent natural antimicrobial and antioxidant agents in the pharmaceutical and food industries.


Assuntos
Farmacorresistência Bacteriana/efeitos dos fármacos , Farmacorresistência Fúngica/efeitos dos fármacos , Óleos Voláteis/química , Óleos Vegetais/química , Dermatopatias Infecciosas/microbiologia , Candida albicans/efeitos dos fármacos , Candida parapsilosis/efeitos dos fármacos , Cassia/química , Linhagem Celular , Citrobacter koseri/efeitos dos fármacos , Cymbopogon/química , Humanos , Klebsiella pneumoniae/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Óleos Voláteis/farmacologia , Origanum/química , Óleos Vegetais/farmacologia , Proteus vulgaris/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Thuja/química , Thymus (Planta)/química
3.
Lett Appl Microbiol ; 69(4): 271-278, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31385615

RESUMO

Antifungal lock therapy has received significant interest in the last few years because the frequently usage of intravascular devices is associated with an increasing number of catheter-related bloodstream infections caused by Candida species. Antifungal combinations with synergistic interaction can be a good choice for antifungal lock therapy; therefore, interactions were examined between two echinocandins (caspofungin and micafungin) and the chitin synthesis inhibitor nikkomycin Z against Candida albicans and C. parapsilosis biofilms. Susceptibility was evaluated using the XTT-based checkerboard microdilution method, while the nature of interactions was assessed by calculating fractional inhibitory concentration indices and using the Bliss independence model. Mathematic-based evaluations were supplemented with fluorescent LIVE/DEAD viability assay. The results obtained by statistical interaction analyses correlated well with the viability assay. The tested echinocandins with nikkomycin Z caused an extended cell death and the structure of the biofilm was sparse compared to the control, especially for C. albicans. The findings support the simultaneous usage of nikkomycin Z and caspofungin or micafungin in alternative therapies such as the antifungal lock therapy. SIGNIFICANCE AND IMPACT OF THE STUDY: Antifungal lock therapy can be a potential therapeutic approach to eradicate the intraluminal Candida biofilms; however, there is no approved lock strategy against fungal species so far. The results of this study provide valuable evidence that nikkomycin Z acts synergistically in combination with caspofungin or micafungin against biofilms. In addition, this synergy was more pronounced for micafungin combined with nikkomycin Z. Therefore, nikkomycin Z can be considered as a potential agent in antifungal lock therapy especially with micafungin against C. albicans or C. parapsilosis biofilms.


Assuntos
Aminoglicosídeos/farmacologia , Antifúngicos/farmacologia , Biofilmes/crescimento & desenvolvimento , Candida albicans/efeitos dos fármacos , Candida parapsilosis/efeitos dos fármacos , Caspofungina/farmacologia , Micafungina/farmacologia , Infecções Relacionadas a Cateter/tratamento farmacológico , Infecções Relacionadas a Cateter/microbiologia , Infecções Relacionadas a Cateter/prevenção & controle , Sinergismo Farmacológico , Humanos , Testes de Sensibilidade Microbiana
4.
J Pak Med Assoc ; 69(8): 1131-1135, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31431766

RESUMO

OBJECTIVE: To evaluate the occurrence and in vitro minimum inhibitory concentrations of different Candida species against nine antifungal agents in blood and urine. METHODS: The prospective descriptive study was conducted at The Children's Hospital, Lahore, Pakistan, from June 2015 to May 2016. Identification of the Candid aspecies was done by API (Analytical Profile Index) Candida (bioMerieux) and in vitro minimum inhibitory concentration break points were reported by using Sensititre Yeast One. Data was analysed using SPSS 20. RESULTS: Of the 87 samples, 68(78.2%) were isolated from blood and 19(21.8%) from urine specimens. Also, 66 (75.9%) samples were non-albicans Candida, 31(35.6%) Candida parapsilosis and 21(24.1%) were Candida albicans. Besides, 83(95.4%) strains exhibited excellent susceptibility pattern with the three echinocandins at minimum inhibitory concentration endpoint of ≤2µg/ml and all (100%) the strains inhibited by ≤1µg/ml of voriconazole. None (0%) of the C. albicans isolates was resistant to an antifungal agent. CONCLUSIONS: Excellent susceptibility pattern against antifungal agents was found with an increasing resistance trend towards non-albicans Candida species.


Assuntos
Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Candidemia/microbiologia , Candidíase/microbiologia , Farmacorresistência Fúngica , Infecções Urinárias/microbiologia , Adolescente , Candida/isolamento & purificação , Candida albicans/efeitos dos fármacos , Candida albicans/isolamento & purificação , Candida parapsilosis/efeitos dos fármacos , Candida parapsilosis/isolamento & purificação , Candidíase Invasiva/microbiologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Testes de Sensibilidade Microbiana , Paquistão
5.
G3 (Bethesda) ; 9(9): 3035-3043, 2019 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-31352406

RESUMO

Candida orthopsilosis is diploid asexual yeast that causes human disease. Most C. orthopsilosis isolates arose from at least four separate hybridizations between related, but not identical, parents. Here, we used population genomics data to correlate genotypic and phenotypic variation in 28 C. orthopsilosis isolates. We used cosine similarity scores to identify 65 variants with potential high-impact (deleterious effects) that correlated with specific phenotypes. Of these, 19 were Single Nucleotide Polymorphisms (SNPs) that changed stop or start codons, or splice sites. One variant resulted in a premature stop codon in both alleles of the gene ZCF29 in C. orthopsilosis isolate 185, which correlated with sensitivity to nystatin and caffeine. We used CRISPR-Cas9 editing to introduce this polymorphism into two resistant C. orthopsilosis isolates. Introducing the stop codon resulted in sensitivity to caffeine and to ketoconazole, but not to nystatin. Our analysis shows that it is possible to associate genomic variants with phenotype in asexual Candida species, but that only a small amount of genomic variation can be easily explored.


Assuntos
Cafeína/farmacologia , Candida parapsilosis/efeitos dos fármacos , Candida parapsilosis/fisiologia , Proteínas Fúngicas/genética , Animais , Antifúngicos/farmacologia , Sistemas CRISPR-Cas , Candida parapsilosis/genética , Candida parapsilosis/patogenicidade , Códon de Terminação , Genótipo , Cetoconazol/farmacologia , Lepidópteros/microbiologia , Testes de Sensibilidade Microbiana , Microrganismos Geneticamente Modificados , Nistatina/farmacologia , Fenótipo , Polimorfismo de Nucleotídeo Único , Virulência/genética
6.
J Med Microbiol ; 68(9): 1353-1358, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31271350

RESUMO

Introduction. Candida auris is a pathogenic yeast that mainly affects immunosuppressed patients and those with implanted medical devices. This pathogen also displays elevated resistance to common antifungals and high survival and spreading capacities. Since no antifungal breakpoints have yet been defined for this pathogen, the data obtained here can be useful for further research concerning treatment or implementation of a prevention and disinfection protocol. Our aim was to study the antifungal resistance of C. auris to current antifungals in planktonic and sessile states. Using confocal laser scanning microscopy and viable biomass production, we demonstrated the ability of C. auris to develop a mature biofilm. We compared the minimal inhibitory concentration (MIC) and the minimal biofilm eradication concentration (MBEC) for the C. auris DSM 21092 strain plus two clinical isolates, and the results were compared with those obtained for Candida albicans and Candida parapsilosis, two species strongly linked to bloodstream infections and infections associated with biomaterials. We found that the clinical isolates of C. auris were resistant to fluconazole and sensitive to echinocandins and polyenes. The C. auris biofilms did not show susceptibility to any antifungal agent, showing MBECs that were up to 512-fold higher than the MICs. These findings highlight the importance of biofilm formation as a key factor underlying the resistance of this species to antifungals and suggest that the presence of implantable medical devices is one of the major risk factors in immunocompromised patients.


Assuntos
Antifúngicos/farmacologia , Biofilmes/efeitos dos fármacos , Candida/efeitos dos fármacos , Candida/isolamento & purificação , Candida albicans/efeitos dos fármacos , Candida parapsilosis/efeitos dos fármacos , Candidíase/microbiologia , Contagem de Colônia Microbiana , Farmacorresistência Fúngica , Equinocandinas/farmacologia , Fluconazol/farmacologia , Humanos , Testes de Sensibilidade Microbiana , Microscopia Confocal , Polienos/farmacologia
7.
Molecules ; 24(14)2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31340530

RESUMO

Solidago species are often used in traditional medicine as anti-inflammatory, diuretic, wound-healing and antimicrobial agents. Still, the bioactive compounds and biological activities of some species have not been studied. The present work aimed to investigate the polyphenolic profile and the biological properties of Solidago graminifolia L. Salisb., a poorly explored medicinal plant. The hydroalcoholic extracts from aerial parts were evaluated for total phenolic content (TPC), total flavonoid content (TFC) and the polyphenolic compounds were investigated by HPLC-MS. The antioxidant potential in vitro was determined using DPPH and FRAP assays. Antibacterial and antifungal effects were evaluated by dilution assays and MIC, MBC and MFC were calculated. The results showed that Solidago graminifolia aerial parts contain an important amount of total phenolics (192.69 mg GAE/g) and flavonoids (151.41 mg RE/g), with chlorogenic acid and quercitrin as major constituents. The hydroalcoholic extracts showed promising antioxidant and antimicrobial potential, with potent antibacterial activity against Staphylococcus aureus and important antifungal effect against Candida albicans and C. parapsilosis. The obtained results indicated that the aerial parts of Solidago graminifolia could be used as novel resource of phytochemicals in herbal preparations with antioxidant and antimicrobial activities.


Assuntos
Anti-Infecciosos/isolamento & purificação , Antioxidantes/isolamento & purificação , Ácido Clorogênico/isolamento & purificação , Flavonoides/isolamento & purificação , Fenóis/isolamento & purificação , Quercetina/análogos & derivados , Solidago/química , Anti-Infecciosos/classificação , Anti-Infecciosos/farmacologia , Antioxidantes/classificação , Antioxidantes/farmacologia , Compostos de Bifenilo/antagonistas & inibidores , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Candida parapsilosis/efeitos dos fármacos , Candida parapsilosis/crescimento & desenvolvimento , Clorofórmio/química , Ácido Clorogênico/farmacologia , Etanol/química , Flavonoides/classificação , Flavonoides/farmacologia , Metanol/química , Testes de Sensibilidade Microbiana , Fenóis/classificação , Fenóis/farmacologia , Picratos/antagonistas & inibidores , Componentes Aéreos da Planta/química , Extratos Vegetais/química , Quercetina/isolamento & purificação , Quercetina/farmacologia , Solventes/química , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento
8.
Microb Pathog ; 132: 282-292, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31082527

RESUMO

Cutaneous fungal infections include onychomycosis, an infection of the nail that affects both healthy and immunocompromised patients. This study investigated the in vitro hydrolytic enzymes production, adhesion and biofilm formation capacity of Candida parapsilosis complex species and Kodamaea ohmeri isolates from onychomycoses of HIV/AIDS patients and also established the antifungal sensitivity profiles of these isolates. Onychomycosis in HIV/AIDS patients showed a high prevalence of emerging yeasts, among which C. parapsilosis complex species and K. ohmeri were the most frequent. Three C. parapsilosis sensu stricto and two C. orthopsilosis isolates were resistant to amphotericin B and 83% of isolates were resistant to terbinafine. All three different species evaluated were proteinase and hemolysin producers. All isolates adhered to stainless steel and siliconized latex surfaces, and carbohydrates intensified adhesion of all isolates. Isolates adhered to keratinous nail and 50% formed biofilms with strong intensity. In multispecies or polymicrobial biofilms, C. albicans and Staphylococcus aureus regulated the biofilm formation of the analyzed species, decreasing the number of their cells in biofilms. The isolation of emerging yeast species from onychomycosis which are great producers of hydrolytic enzymes and with high adhesion and biofilm formation capacity is a result that should be considered relevant in clinical practice. In addition, half of the isolates was resistant to at least one of the tested antifungals. Taken together these data corroborate the infectious capacity and viability of these isolates under favorable conditions.


Assuntos
Síndrome de Imunodeficiência Adquirida/complicações , Candida parapsilosis/isolamento & purificação , Onicomicose/microbiologia , Saccharomycetales/isolamento & purificação , Adulto , Anfotericina B/farmacologia , Antifúngicos/farmacologia , Biofilmes/crescimento & desenvolvimento , Candida parapsilosis/efeitos dos fármacos , DNA Fúngico , Farmacorresistência Fúngica , Feminino , HIV , Humanos , Látex , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Onicomicose/epidemiologia , Saccharomycetales/efeitos dos fármacos , Aço Inoxidável , Terbinafina/farmacologia , Virulência , Adulto Jovem
9.
J Chemother ; 31(3): 137-140, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30955472

RESUMO

Candidemia is a common invasive fungal infection with a high mortality rate. We performed a retrospective audit of candidemia at a tertiary centre in Western Australia, 2005-2014. There were 167 episodes of candidemia due to 173 isolates of Candida. Candida albicans (40.5%), Candida glabrata complex (30.6%), Candida parapsilosis complex (14.4%) were the most common species causing candidemia across the study. Of the tested isolates, 17.7% (11/62) were non-susceptible to fluconazole and 13.6% (9/66) non-susceptible to caspofungin. 22.8% (8/35) C. glabrata complex were fluconazole resistant and 17.1% (6/35) were non-susceptible to caspofungin. Candida glabrata complex was more common in the latter time period, but there were no susceptibility changes over time. In our setting, the prevalence of C. glabrata complex and antifungal non-susceptibility is high, and the prevalence of C. glabrata complex is increasing.


Assuntos
Antifúngicos/farmacologia , Candida parapsilosis/isolamento & purificação , Candidemia/epidemiologia , Candidemia/microbiologia , Farmacorresistência Fúngica , Austrália/epidemiologia , Candida parapsilosis/efeitos dos fármacos , Candidemia/tratamento farmacológico , Humanos , Testes de Sensibilidade Microbiana , Prevalência , Estudos Retrospectivos
10.
Rev. esp. quimioter ; 32(2): 183-188, abr. 2019. tab, graf
Artigo em Inglês | IBECS | ID: ibc-182820

RESUMO

Objetivos. Candida albicans continúa siendo la causa más frecuente de candidiasis invasiva; sin embargo, la incidencia de candidiasis causadas por especies diferentes a C. albicans, como Candida parapsilosis, está aumentando. El efecto postantifúngico (PAFE) es relevante para establecer pautas de dosificación en la terapia antifúngica, ya que la frecuencia de administración de los fármacos antifúngicos podría cambiar dependiendo del PAFE. El objetivo de este estudio fue evaluar el PAFE de anidulafungina contra C. albicans, Candida dubliniensis, Candida africana, C. parapsilosis, Candida metapsilosis y Candida orthopsilosis. Material y métodos: Se evaluaron 21 cepas de Candida. Para llevar a cabo los estudios PAFE, las células se expusieron durante 1 h a concentraciones entre 0,12 y 8 mg/L de anidulafungina. Las curvas de letalidad (TK) se obtuvieron empleando las mismas concentraciones. Los experimentos se realizaron utilizando un inóculo de 1-5 x 105 células/mL, durante 48 h de incubación. Las lecturas de PAFE y TK se realizaron a las 0, 2, 4, 6, 24 y 48 h. Resultados: Anidulafungina, en los experimentos PAFE, fue fungicida contra 2 de 14 (14%) cepas de las especies relacionadas con C. albicans y ejerció un PAFE prolongado (≥ 33,6 h) contra 13 de 14 (93%) cepas (2 mg/L). El límite fungicida de anidulafungina se alcanzó contra 1 de 7 (14%) cepas del complejo C. parapsilosis, con un PAFE prolongado (≥ 42 h) contra 6 de 7 (86%) cepas. Conclusiones: Anidulafungina produce un PAFE significativo y prolongado contra C. albicans y C. parapsilosis y las especies relacionadas con estas


Objectives: Candida albicans remains the most common aetiology of invasive candidiasis, leading to high morbidity and mortality. Nevertheless, the incidence of candidiasis due to non-C. albicans species, such as Candida parapsilosis, is increasing. Postantifungal effect (PAFE) is relevant for establishing dosage schedules in antifungal therapy, as the frequency of antifungal administration could change depending on PAFE. The aim of this study was to evaluate the PAFE of anidulafungin against C. albicans, Candida dubliniensis, Candida africana, C. parapsilosis, Candida metapsilosis and Candida orthopsilosis. Material and methods: Twenty-one Candida strains were evaluated. Cells were exposed to anidulafungin for 1 h at concentrations ranging from 0.12 to 8 mg/L for PAFE studies. Time-kill experiments (TK) were conducted at the same concentrations. The experiments were performed using an inoculum of 1-5 x 105 cells/mL and 48 h incubation. Readings of PAFE and TK were done at 0, 2, 4, 6, 24 and 48 h. Results: Anidulafungin was fungicidal against 2 out of 14 (14%) strains of C. albicans related species in PAFE experiments. Moreover, 2 mg/L of anidulafungin exerted a prolonged PAFE (≥ 33.6 h) against 13 out of 14 (93%) strains. Similarly, fungicidal endpoint was achieved against 1 out of 7 (14%) strains of C. parapsilosis complex, being PAFE prolonged (≥ 42 h) against 6 out of 7 (86%) strains. Conclusions: Anidulafungin induced a significant and prolonged PAFE against C. albicans and C. parapsilosis and their related species


Assuntos
Humanos , Anidulafungina/farmacocinética , Candida albicans/efeitos dos fármacos , Candida parapsilosis/efeitos dos fármacos , Candida/efeitos dos fármacos , Candidíase/tratamento farmacológico , Antifúngicos/farmacocinética , Técnicas In Vitro/métodos , Candida/patogenicidade
11.
Rev Iberoam Micol ; 36(1): 24-29, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30837186

RESUMO

BACKGROUND: Candida parapsilosis, Candida metapsilosis and Candida orthopsilosis are emerging as relevant causes of candidemia. Moreover, they show differences in their antifungal susceptibility and virulence. The echinocandins are different in terms of in vitro antifungal activity against Candida. Time-kill (TK) curves represent an excellent approach to evaluate the fungicidal activity of antifungal drugs. AIMS: To compare the fungicidal activities of anidulafungin, caspofungin and micafungin against C. parapsilosis species complex by TK curves. METHODS: Antifungal activities of three echinocandins against C. parapsilosis, C. metapsilosis and C. orthopsilosis were studied by TK curves. Drug concentrations assayed were 0.25, 2 and 8µg/ml. CFU/ml were determined at 0, 2, 4, 6, 24 and 48h. RESULTS: Killing activities of echinocandins were species-, isolates- and concentration-dependent. Anidulafungin reached the fungicidad endpoint for 6 out of 7 isolates (86%); it required between 13.34 and 29.67h to reach this endpoint for the three species studied, but more than 48h were needed against one isolate of C. orthopsilosis (8µg/ml). Caspofungin fungicidal endpoint was only achieved with 8µg/ml against one isolate of C. metapsilosis after 30.12h (1 out of 7 isolates; 14%). Micafungin fungicidal endpoint was reached in 12.74-28.38h (8µg/ml) against one isolate each of C. parapsilosis and C. orthopsilosis, and against both C. metapsilosis isolates (4 out of 7 isolates; 57%). CONCLUSIONS: C. metapsilosis was the most susceptible species to echinocandins, followed by C. orthopsilosis and C. parapsilosis. Anidulafungin was the most active echinocandin against C. parapsilosis complex.


Assuntos
Anidulafungina/farmacocinética , Antifúngicos/farmacocinética , Candida parapsilosis/efeitos dos fármacos , Caspofungina/farmacocinética , Micafungina/farmacocinética , Testes de Sensibilidade Microbiana , Fatores de Tempo
12.
Clin Microbiol Rev ; 32(2)2019 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-30814115

RESUMO

Patients with suppressed immunity are at the highest risk for hospital-acquired infections. Among these, invasive candidiasis is the most prevalent systemic fungal nosocomial infection. Over recent decades, the combined prevalence of non-albicans Candida species outranked Candida albicans infections in several geographical regions worldwide, highlighting the need to understand their pathobiology in order to develop effective treatment and to prevent future outbreaks. Candida parapsilosis is the second or third most frequently isolated Candida species from patients. Besides being highly prevalent, its biology differs markedly from that of C. albicans, which may be associated with C. parapsilosis' increased incidence. Differences in virulence, regulatory and antifungal drug resistance mechanisms, and the patient groups at risk indicate that conclusions drawn from C. albicans pathobiology cannot be simply extrapolated to C. parapsilosis Such species-specific characteristics may also influence their recognition and elimination by the host and the efficacy of antifungal drugs. Due to the availability of high-throughput, state-of-the-art experimental tools and molecular genetic methods adapted to C. parapsilosis, genome and transcriptome studies are now available that greatly contribute to our understanding of what makes this species a threat. In this review, we summarize 10 years of findings on C. parapsilosis pathogenesis, including the species' genetic properties, transcriptome studies, host responses, and molecular mechanisms of virulence. Antifungal susceptibility studies and clinician perspectives are discussed. We also present regional incidence reports in order to provide an updated worldwide epidemiology summary.


Assuntos
Candida parapsilosis/genética , Candidíase/epidemiologia , Infecção Hospitalar/epidemiologia , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candida parapsilosis/efeitos dos fármacos , Candida parapsilosis/patogenicidade , Candidíase/tratamento farmacológico , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/microbiologia , Perfilação da Expressão Gênica , Humanos , Incidência , Testes de Sensibilidade Microbiana , Análise de Sequência de DNA , Análise de Sequência de RNA
13.
Rev. iberoam. micol ; 36(1): 24-29, ene.-mar. 2019. graf, tab
Artigo em Inglês | IBECS | ID: ibc-185489

RESUMO

Background: Candida parapsilosis, Candida metapsilosis and Candida orthopsilosis are emerging as relevant causes of candidemia. Moreover, they show differences in their antifungal susceptibility and virulence. The echinocandins are different in terms of in vitro antifungal activity against Candida. Time-kill (TK) curves represent an excellent approach to evaluate the fungicidal activity of antifungal drugs. Aims: To compare the fungicidal activities of anidulafungin, caspofungin and micafungin against C. parapsilosis species complex by TK curves. Methods: Antifungal activities of three echinocandins against C. parapsilosis, C. metapsilosis and C. orthopsilosis were studied by TK curves. Drug concentrations assayed were 0.25, 2 and 8 μg/ml. CFU/ml were determined at 0, 2, 4, 6, 24 and 48 h. Results: Killing activities of echinocandins were species-, isolates- and concentration-dependent. Anidulafungin reached the fungicidad endpoint for 6 out of 7 isolates (86%); it required between 13.34 and 29.67h to reach this endpoint for the three species studied, but more than 48h were needed against one isolate of C. orthopsilosis (8 μg/ml). Caspofungin fungicidal endpoint was only achieved with 8μg/ml against one isolate of C. metapsilosis after 30.12 h (1 out of 7 isolates; 14%). Micafungin fungicidal endpoint was reached in 12.74-28.38h (8μg/ml) against one isolate each of C. parapsilosis and C. orthopsilosis, and against both C. metapsilosis isolates (4 out of 7 isolates; 57%). Conclusions: C. metapsilosis was the most susceptible species to echinocandins, followed by C. orthopsilosis and C. parapsilosis. Anidulafungin was the most active echinocandin against C. parapsilosis complex


Antecedentes: Candida parapsilosis, Candida metapsilosis y Candida orthopsilosis son causas relevantes de candidemia. Además, muestran diferencias en la sensibilidad a los fármacos antifúngicos. Las equinocandinas muestran diferente actividad antifúngica in vitro frente a Candida. Las curvas de tiempo-letalidad (TK) representan una excelente aproximación para evaluar la actividad fungicida de los fármacos antifúngicos. Objetivos: Comparar la actividad fungicida de la anidulafungina, la caspofungina y la micafungina frente al complejo C. parapsilosis mediante las curvas de TK. Métodos: Se estudió la actividad de tres equinocandinas frente a C. parapsilosis, C. metapsilosis y C. orthopsilosis mediante las curvas de TK. Las concentraciones ensayadas fueron 0,25, 2 y 8 μg/ml. Se determinaron las UFC/ml a las 0, 2, 4, 6, 24 y 48 h. Resultados: La actividad de las equinocandinas fue especie-, aislamiento- y concentración-dependiente. La anidulafungina alcanzó el límite fungicida frente a 6 de 7 aislamientos (86%), y necesitó 13,34-29,67h para alcanzar este límite en las tres especies estudiadas; para un aislamiento de C. orthopsilosis, requirió más de 48h (8μg/ml). El límite fungicida de la caspofungina solo se alcanzó con 8 μg/ml frente a un aislamiento de C. metapsilosis después de 30,12h (1 de 7 aislamientos; 14%). La micafungina alcanzó este límite en 12,74-28,38 h (8 μg/ml) frente a un aislamiento de C. parapsilosis y C. orthopsilosis y frente a ambos aislamientos de C. metapsilosis (4 de 7 aislamientos; 57%). Conclusiones: C. metapsilosis fue la especie más sensible a las equinocandinas, seguida de C. orthopsilosis y C. parapsilosis. La anidulafungina fue la equinocandina más activa frente al complejo C. parapsilosis


Assuntos
Anidulafungina/farmacocinética , Antifúngicos/farmacocinética , Candida parapsilosis/efeitos dos fármacos , Caspofungina/farmacocinética , Micafungina/farmacocinética , Testes de Sensibilidade Microbiana , Fatores de Tempo
14.
Rev. iberoam. micol ; 36(1): 44-47, ene.-mar. 2019. tab
Artigo em Inglês | IBECS | ID: ibc-185494

RESUMO

Background: Candida parapsilosis may acquire resistance to echinocandins, a fact that prompts the search for new therapeutic options. Aims: The present study aimed to evaluate the in vitro activity of antifungal agents, alone and in combination, against four groups of C. parapsilosis strains: (1) echinocandin-susceptible (ES) clinical isolates (MIC ≤ 2 μg/ml), (2) anidulafungin-resistant strains (MIC ≥ 8 μg/ml), (3) caspofungin-resistant strains (MIC ≥ 8 μg/ml), and (4) micafungin-resistant strains (MIC ≥ 8 μg/ml). Methods: Antifungal interactions were evaluated by a checkerboard micro-dilution method. The determination of the MIC to each drug for every isolate according to the Clinical and Laboratory Standards Institute documents M27 (2017) and M60 (2017) was also done. Results: The echinocandins-resistant (ER) strains showed higher MICs to the tested antifungals than the ES strains, except for amphotericin B, for which the ER groups remained susceptible. Conclusions: Most combinations showed indifferent interactions. The use of monotherapy still seems to be the best option. As resistance to echinocandins is an emergent phenomenon, further studies are required to provide clearer information on the susceptibility differences between strains to these antifungal agents


Antecedentes: Candida parapsilosis puede volverse resistente a las equinocandinas, lo que requiere la búsqueda de nuevas opciones terapéuticas. Objetivos: El presente estudio tenía como objetivo evaluar la actividad in vitro de algunos antifúngicos, solos y en combinación, frente a cuatro grupos de cepas de C. parapsilosis: 1) cepas clínicas sensibles a las equinocandinas (SE) (CIM ≤ 2 μg/ml), 2) cepas resistentes a la anidulafungina (CIM ≥ 8 μg/ml), 3) cepas resistentes a la caspofungina (CIM ≥ 8 μg/ml) y 4) cepas resistentes a la micafungina (CIM ≥ 8 μg/ml). Métodos: Se evaluaron las interacciones de los antifúngicos con el método de microdilución en damero. También se determinó el valor de la CIM de cada cepa en cada antifúngico de acuerdo con los documentos Clinical and Laboratory Standards Institute M27 (2017) y M60 (2017). Resultados: Las cepas resistentes a las equinocandinas (RE) presentaron los valores de CIM más altos a los antifúngicos probados que las cepas SE a excepción de la anfotericina B, frente a la cual los grupos RE se mantuvieron sensibles. Conclusiones: La mayoría de las combinaciones evidenciaron interacciones indiferentes. El uso de monoterapias aún parece la mejor opción. Puesto que la resistencia a las equinocandinas es un fenómeno emergente, se requieren estudios adicionales con el fin de proporcionar una información más clara acerca de las diferencias de sensibilidad de diferentes cepas a estos antifúngicos


Assuntos
Animais , Antifúngicos/farmacologia , Candida parapsilosis/efeitos dos fármacos , Equinocandinas/farmacologia , Candida parapsilosis/classificação , Farmacorresistência Fúngica , Quimioterapia Combinada , Testes de Sensibilidade Microbiana
15.
Med Mycol ; 57(8): 1024-1037, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30753649

RESUMO

Candida parapsilosis sensu stricto (C. parapsilosis) has emerged as the second/third commonest Candida species isolated from hospitals worldwide. Candida spp. possess numerous virulence attributes, including peptidases that play multiple roles in both physiological and pathological events. So, fungal peptidases are valid targets for new drugs development. With this premise in mind, we have evaluated the effect of serine peptidase inhibitors (SPIs) on both cell biology and virulence aspects of C. parapsilosis. First, five different SPIs, phenylmethylsulfonyl fluoride, benzamidine, 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride, N-α-tosyl-L-lysine chloromethyl ketone hydrochloride, and N-tosyl-L-phenylalanine chloromethyl ketone (TPCK) were tested, and TPCK showed the best efficacy to arrest fungal growth. Subsequently, the ability of TPCK to modulate physiopathological processes was investigated. Overall, TPCK was able to (i) inhibit the cell-associated serine peptidase activities, (ii) promote morphometric and ultrastructural alterations, (iii) induce an increase in the intracellular oxidation level, which culminates in a vigorous lipid peroxidation and accumulation of neutral lipids in cytoplasmic inclusions, (iv) modulate the expression/exposition of surface structures, such as mannose/glucose-rich glycoconjugates, N-acetylglucosamine-containing molecules, chitin, polypeptides and surface aspartic peptidases, (v) reduce the adhesion to either polystyrene or glass surfaces as well as to partially disarticulate the mature biofilm, (vi) block the fungal interaction with macrophages, and (vii) protect Galleria mellonella from fungal infection, enhancing larvae survivability. Altogether, these results demonstrated that TPCK induced several changes over fungal biology besides the interference with aspects associated to C. parapsilosis virulence and pathogenesis, which indicates that SPIs could be novel promising therapeutic agents in dealing with candidiasis.


Assuntos
Antifúngicos/farmacologia , Candida parapsilosis/efeitos dos fármacos , Candidíase/prevenção & controle , Inibidores de Serino Proteinase/farmacologia , Tosilfenilalanil Clorometil Cetona/farmacologia , Animais , Antifúngicos/administração & dosagem , Candida parapsilosis/citologia , Candida parapsilosis/crescimento & desenvolvimento , Adesão Celular/efeitos dos fármacos , Modelos Animais de Doenças , Larva/microbiologia , Lepidópteros/microbiologia , Estresse Oxidativo , Inibidores de Serino Proteinase/administração & dosagem , Análise de Sobrevida , Tosilfenilalanil Clorometil Cetona/administração & dosagem , Resultado do Tratamento , Virulência/efeitos dos fármacos
16.
Rev Iberoam Micol ; 36(1): 44-47, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30691952

RESUMO

BACKGROUND: Candida parapsilosis may acquire resistance to echinocandins, a fact that prompts the search for new therapeutic options. AIMS: The present study aimed to evaluate the in vitro activity of antifungal agents, alone and in combination, against four groups of C. parapsilosis strains: (1) echinocandin-susceptible (ES) clinical isolates (MIC ≤ 2µg/ml), (2) anidulafungin-resistant strains (MIC ≥ 8µg/ml), (3) caspofungin-resistant strains (MIC ≥ 8µg/ml), and (4) micafungin-resistant strains (MIC ≥ 8µg/ml). METHODS: Antifungal interactions were evaluated by a checkerboard micro-dilution method. The determination of the MIC to each drug for every isolate according to the Clinical and Laboratory Standards Institute documents M27 (2017) and M60 (2017) was also done. RESULTS: The echinocandins-resistant (ER) strains showed higher MICs to the tested antifungals than the ES strains, except for amphotericin B, for which the ER groups remained susceptible. CONCLUSIONS: Most combinations showed indifferent interactions. The use of monotherapy still seems to be the best option. As resistance to echinocandins is an emergent phenomenon, further studies are required to provide clearer information on the susceptibility differences between strains to these antifungal agents.


Assuntos
Antifúngicos/farmacologia , Candida parapsilosis/efeitos dos fármacos , Equinocandinas/farmacologia , Candida parapsilosis/classificação , Farmacorresistência Fúngica , Quimioterapia Combinada , Testes de Sensibilidade Microbiana
17.
FEMS Yeast Res ; 19(2)2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30476044

RESUMO

Candida albicans ATCC 14053 and Candida parapsilosis ATCC 22019 hyphal-wall protein 1 (HWP1) are involved in hyphae formation and pathogenesis. The transcriptional agglutinin-like sequence 3 (ALS3) genes in both species are responsible for the development of biofilm and colonization on tooth surfaces. Therefore, we investigated the expression of HWP1 and ALS3 quantitatively in C. albicans and C. parapsilosis and examined the biofilm structure upon exposure to various nicotine concentrations. In vitro, biofilms of Candida species were developed directly on slides using the Lab-Tek Chamber Slide System and visualized by confocal laser scanning microscopy. Quantitative real-time polymerase chain reaction was used to measure HWP1 and ALS3 expression in C. albicans ATCC 14053 and C. parapsilosis ATCC 22019. The results indicated that nicotine multiplied the number of yeast cells and increased the extracellular polysaccharides of Candida species. We also found that 1-2 mg/mL nicotine could enhance the formation of biofilm. The findings also revealed that the expression of HWP1 and ALS3 in Candida species were increased as the nicotine concentration increased. Therefore, nicotine influences the biofilm development of oral-associated C. albicans ATCC 14053 and C. parapsilosis ATCC 22019.


Assuntos
Biofilmes/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Candida parapsilosis/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Nicotina/metabolismo , Biofilmes/crescimento & desenvolvimento , Candida albicans/fisiologia , Candida parapsilosis/fisiologia , Proteínas Fúngicas/análise , Proteínas Fúngicas/genética , Perfilação da Expressão Gênica , Glicoproteínas de Membrana/análise , Glicoproteínas de Membrana/genética , Técnicas Microbiológicas , Microscopia Confocal , Polissacarídeos/metabolismo , Reação em Cadeia da Polimerase em Tempo Real
18.
Sci Total Environ ; 650(Pt 1): 1231-1238, 2019 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-30308811

RESUMO

This work investigated the phenotypic behavior of Candida parapsilosis species complex in response to exposure to agricultural azoles and fluconazole. Three fluconazole-susceptible strains of C. parapsilosis sensu stricto, C. orthopsilosis and C. metapsilosis were used. Initial minimum inhibitory concentrations (iMICs) for agricultural and clinical azoles were determined by broth microdilution. Then, the strains were exposed to tebuconazole, tetraconazole and fluconazole for 15 days, at concentrations that were two-folded daily, starting at one-eighth the iMIC (iMIC/8) up to 64 times iMIC (64xiMIC). After 15-day-exposure, antifungal susceptibility, biofilm formation, CDR, MDR and ERG expression were evaluated. The three cryptic species developed tolerance to the antifungals they were exposed and presented reduction (P < 0.05) in fluconazole susceptibility. In addition, C. parapsilosis sensu stricto and C. metapsilosis also presented reduced susceptibility to voriconazole, after fluconazole exposure. Azole exposure decreased (P < 0.05) biofilm production by C. parapsilosis sensu stricto and C. orthopsilosis and increased (P < 0.05) the expression of ERG11 in all tested strains. The results show that exposure to agricultural azoles and fluconazole induces changes in the phenotypic behavior and gene expression by the three cryptic species of C. parapsilosis complex, highlighting the importance of environmental determinants for the development of antifungal resistance.


Assuntos
Antifúngicos/toxicidade , Azóis/toxicidade , Candida parapsilosis/efeitos dos fármacos , Agricultura , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Candida parapsilosis/fisiologia , Clorobenzenos , Testes de Sensibilidade Microbiana , Triazóis
19.
Med Mycol ; 57(3): 291-299, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-29846682

RESUMO

Vulvovaginal candidiasis (VVC) is the second most common cause of vaginitis after bacterial vaginosis, affecting millions of women worldwide every year. Candida albicans is the most frequent agent of VVC followed by other species of Candida such as C. glabrata and C. parapsilosis. Out of a total of 100 clinical isolates of Candida spp. obtained from patients diagnosed with VVC, 84 were identified as C. albicans, while the remaining isolates were identified as non--albicans Candida strains. Phospholipases and proteinases were produced by a majority of the C. albicans strains and esterases and hemolysins a minority of these strains. Among the non-C. albicans strains, only a few of the strains produced these proteins. Nearly all of the isolates formed biofilms. Our results showed that the butoconazole, clotrimazole, and fluconazole were active against C. albicans and less so against the non-albicans Candida strains. The MIC90 of amphotericin B and nystatins were 2 and 4 µg/ml, respectively, against either C. albicans or non-albicans Candida spp. Representative ceragenins (CSA-13, CSA-131, and CSA-138), developed as mimics of endogenous antimicrobial peptides, were active against fluconazole-resistant strains, both alone and in combination with fluconazole. These results suggest the potential use of ceragenins in treating VVC, including infections caused by fluconazole-resistant isolates.


Assuntos
Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Candidíase Vulvovaginal/microbiologia , Esteroides/farmacologia , Biofilmes/efeitos dos fármacos , Candida/enzimologia , Candida/isolamento & purificação , Candida albicans/efeitos dos fármacos , Candida glabrata/efeitos dos fármacos , Candida parapsilosis/efeitos dos fármacos , Farmacorresistência Fúngica , Esterases/metabolismo , Feminino , Fluconazol/farmacologia , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Peptídeo Hidrolases/metabolismo , Fosfolipases/metabolismo , Fatores de Virulência
20.
mSphere ; 3(6)2018 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-30429225

RESUMO

Candida species are a major cause of life-threatening bloodstream infections worldwide. Although Candida albicans is responsible for the vast majority of infections, the clinical relevance of other Candida species has also emerged over the last twenty years. This shift might be due in part to changes in clinical guidelines, as echinocandins became the first line of therapeutics for the treatment. Candida parapsilosis is an emerging non-albicans Candida species that exhibits lower susceptibility levels to these drugs. Candida species frequently display resistance to echinocandins, and the mechanism for this is well-known in C. albicans and Candida glabrata, where it is mediated by amino acid substitutions at defined locations of the ß-1,3-glucan synthase, Fks1p. In C. parapsilosis isolates, Fks1p harbors an intrinsic amino acid change at position 660 of the hot spot 1 (HS1) region, which is thought to be responsible for the high MIC values. Less is known about acquired substitutions in this species. In this study, we used directed evolution experiments to generate C. parapsilosis strains with acquired resistance to caspofungin, anidulafungin, and micafungin. We showed that cross-resistance was dependent on the type of echinocandin used to generate the evolved strains. During their characterization, all mutant strains showed attenuated virulence in vivo and also displayed alterations in the exposure of inner cell wall components. The evolved strains harbored 251 amino acid changes, including three in the HS1, HS2, and HS3 regions of Fks1p. Altogether, our results demonstrate a direct connection between acquired antifungal resistance and virulence of C. parapsilosis IMPORTANCE Candida parapsilosis is an opportunistic fungal pathogen with the ability to cause infections in immunocompromised patients. Echinocandins are the currently recommended first line of treatment for all Candida species. Resistance of Candida albicans to this drug type is well characterized. C. parapsilosis strains have the lowest in vitro susceptibility to echinocandins; however, patients with such infections typically respond well to echinocandin therapy. There is little knowledge of acquired resistance in C. parapsilosis and its consequences on other characteristics such as virulence properties. In this study, we aimed to dissect how acquired echinocandin resistance influences the pathogenicity of C. parapsilosis and to develop explanations for why echinocandins are clinically effective in the setting of acquired resistance.


Assuntos
Antifúngicos/farmacologia , Candida parapsilosis/efeitos dos fármacos , Candida parapsilosis/crescimento & desenvolvimento , Farmacorresistência Fúngica , Equinocandinas/farmacologia , Estresse Fisiológico , Candida parapsilosis/genética , Análise Mutacional de DNA , Glucosiltransferases/genética , Testes de Sensibilidade Microbiana , Mutação de Sentido Incorreto , Virulência
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