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1.
J Med Microbiol ; 70(7)2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34259620

RESUMO

Introduction. The presence of Candida biofilms in medical devices is a concerning and important clinical issue for haemodialysis patients who require constant use of prosthetic fistulae and catheters.Hypothesis/Gap Statement. This prolonged use increases the risk of candidaemia due to biofilm formation. PH151 and clioquinol are 8-hydroxyquinoline derivatives that have been studied by our group and showed interesting anti-Candida activity.Aim. This study evaluated the biofilm formation capacity of Candida species on polytetrafluoroethylene (PTFE) and polyurethane (PUR) and investigated the synergistic effects between the compounds PH151 and clioquinol and fluconazole, amphotericin B and caspofungin against biofilm cells removed from those materials. Further, the synergistic combination was evaluated in terms of preventing biofilm formation on PTFE and PUR discs.Methodology. Susceptibility testing was performed for planktonic and biofilm cells using the broth microdilution method. The checkerboard method and the time-kill assay were used to evaluate the interactions between antifungal agents. Antibiofilm activity on PTFE and PUR materials was assessed to quantify the prevention of biofilm formation.Results. Candida albicans, Candida glabrata and Candida tropicalis showed ability to form biofilms on both materials. By contrast, Candida parapsilosis did not demonstrate this ability. Synergistic interaction was observed when PH151 was combined with fluconazole in 77.8 % of isolates and this treatment was shown to be concentration- and time-dependent. On the other hand, indifferent interactions were predominantly observed with the other combinations. A reduction in biofilm formation on PUR material of more than 50 % was observed when using PH151 combined with fluconazole.Conclusion. PH151 demonstrated potential as a local treatment for use in a combination therapy approach against Candida biofilm formation on haemodialysis devices.


Assuntos
Antifúngicos/farmacologia , Biofilmes/efeitos dos fármacos , Candida/efeitos dos fármacos , Contaminação de Equipamentos/prevenção & controle , Fluconazol/farmacologia , Sulfonamidas/farmacologia , Candida/classificação , Candida/fisiologia , Candidíase/microbiologia , Humanos , Testes de Sensibilidade Microbiana , Oxiquinolina/farmacologia , Diálise Renal
2.
Int J Mol Sci ; 22(12)2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34208638

RESUMO

Fatty acids are derived from diet and fermentative processes by the intestinal flora. Two to five carbon chain fatty acids, termed short chain fatty acids (SCFA) are increasingly recognized to play a role in intestinal homeostasis. However, the characteristics of slightly longer 6 to 10 carbon, medium chain fatty acids (MCFA), derived primarily from diet, are less understood. Here, we demonstrated that SCFA and MCFA have divergent immunomodulatory propensities. SCFA down-attenuated host pro-inflammatory IL-1ß, IL-6, and TNFα response predominantly through the TLR4 pathway, whereas MCFA augmented inflammation through TLR2. Butyric (C4) and decanoic (C10) acid displayed most potent modulatory effects within the SCFA and MCFA, respectively. Reduction in TRAF3, IRF3 and TRAF6 expression were observed with butyric acid. Decanoic acid induced up-regulation of GPR84 and PPARγ and altered HIF-1α/HIF-2α ratio. These variant immune characteristics of the fatty acids which differ by just several carbon atoms may be attributable to their origins, with SCFA being primarily endogenous and playing a physiological role, and MCFA exogenously from the diet.


Assuntos
Ácidos Graxos Voláteis/metabolismo , Ácidos Graxos/metabolismo , Imunomodulação , Biomarcadores , Ácido Butírico/metabolismo , Candida/fisiologia , Citocinas/metabolismo , Dieta , Microbioma Gastrointestinal , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Imunomodulação/genética , Mediadores da Inflamação/metabolismo , Receptor 4 Toll-Like/metabolismo
3.
Can J Microbiol ; 67(7): 497-505, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34232751

RESUMO

To colonize and infect the host, arthroconidial yeasts must avoid being killed by the host's defenses. The formation of biofilms on implanted devices allows fungi to avoid host responses and to disseminate into the host. To better study the mechanisms of infection by arthroconidial yeasts, adherence and biofilm formation were assayed using patient samples collected over 10 years. In clinical samples, adherence varies within species, but the relative adherence is constant for those samples isolated from the same infection site. Herein we document, for the first time, in-vitro biofilm formation by Trichosporon dohaense, T. ovoides, T. japonicum, T. coremiiforme, Cutaneotrichosporon mucoides, Cutaneotrichosporon cutaneum, Galactomyces candidus, and Magnusiomyces capitatus on clinically relevant catheter material. Analysis of biofilm biomass assays indicated that biofilm mass changes less than 2-fold, regardless of the species. Our results support the hypothesis that most pathogenic fungi can form biofilms, and that biofilm formation is a source of systemic infections.


Assuntos
Biofilmes , Candida/fisiologia , Micoses/microbiologia , Leveduras/fisiologia , Candida/classificação , Candida/genética , Candida/isolamento & purificação , Humanos , Leveduras/classificação , Leveduras/genética , Leveduras/isolamento & purificação
4.
Arch Microbiol ; 203(7): 4461-4473, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34142183

RESUMO

A cultivated form of bacteria (strain 2202) was isolated from the hemal fluid of the bivalve mollusk Modiolus kurilensis. Based on the set of data collected by genetic and physiological/biochemical analyses, the strain was identified as the species Pseudoalteromonas piscicida. Strain 2202 exhibits antimicrobial activity against Staphylococcus aureus, Candida albicans, and Bacillus subtilis but not against Escherichia coli and Pseudomonas aeruginosa. These activities characterize the behavior of strain 2202 as predator-like and classify it as a facultative predator. Being part of the normal microflora in the hemolymph of M. kurilensis, when external conditions change, strain 2202 shows features of opportunistic microflora. The strain 2202 exhibits selective toxicity towards larvae of various invertebrates: it impairs the early development of Mytilus edulis, but not of Strongylocentrotus nudus. Thus, the selective manner in which P. piscicida strains interact with various species of microorganisms and eukaryotes should be taken into consideration when using their biotechnological potential as a probiotic in aquaculture, source of antimicrobial substances, and factors that prevent fouling.


Assuntos
Bivalves , Pseudoalteromonas , Animais , Fenômenos Fisiológicos Bacterianos , Bivalves/microbiologia , Candida/fisiologia , Hemolinfa/microbiologia , Interações Microbianas , Pseudoalteromonas/isolamento & purificação , Pseudoalteromonas/metabolismo , Pseudoalteromonas/fisiologia
5.
Nat Commun ; 12(1): 3897, 2021 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-34162835

RESUMO

A major health concern of the 21st century is the rise of multi-drug resistant pathogenic microbial species. Recent technological advancements have led to considerable opportunities for low-dimensional materials (LDMs) as potential next-generation antimicrobials. LDMs have demonstrated antimicrobial behaviour towards a variety of pathogenic bacterial and fungal cells, due to their unique physicochemical properties. This review provides a critical assessment of current LDMs that have exhibited antimicrobial behaviour and their mechanism of action. Future design considerations and constraints in deploying LDMs for antimicrobial applications are discussed. It is envisioned that this review will guide future design parameters for LDM-based antimicrobial applications.


Assuntos
Anti-Infecciosos/farmacologia , Bactérias/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Candida/efeitos dos fármacos , Micoses/tratamento farmacológico , Anti-Infecciosos/química , Bactérias/crescimento & desenvolvimento , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Biofilmes/crescimento & desenvolvimento , Candida/fisiologia , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Humanos , Micoses/microbiologia , Nanoestruturas/administração & dosagem , Nanoestruturas/química , Tamanho da Partícula
6.
Bioorg Chem ; 110: 104771, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33714761

RESUMO

Azole antifungals are commonly used to treat fungal infections but have resulted in the occurrence of drug resistance. Therefore, developing azole derivatives (AZDs) that can both combat established drug-resistant fungal strains and evade drug resistance is of great importance. In this study, we synthesized a series of AZDs with a fluconazole (FLC) skeleton conjugated with a mitochondria-targeting triphenylphosphonium cation (TPP+). These AZDs displayed potent activity against both azole-sensitive and azole-resistant Candida strains without eliciting obvious resistance. Moreover, two representative AZDs, 20 and 25, exerted synergistic antifungal activity with Hsp90 inhibitors against C. albicans strains resistant to the combination treatment of FLC and Hsp90 inhibitors. AZD 25, which had minimal cytotoxicity, was effective in preventing C. albicans biofilm formation. Mechanistic investigation revealed that AZD 25 inhibited the biosynthesis of the fungal membrane component ergosterol and interfered with mitochondrial function. Our findings provide an alternative approach to address fungal resistance problems.


Assuntos
Antifúngicos/síntese química , Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Farmacorresistência Fúngica , Compostos Organofosforados/síntese química , Compostos Organofosforados/farmacologia , Células A549 , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Candida/fisiologia , Sobrevivência Celular , Humanos , Estrutura Molecular , Células PC-3
7.
PLoS Comput Biol ; 17(3): e1008817, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33735173

RESUMO

Developing mathematical models to accurately predict microbial growth dynamics remains a key challenge in ecology, evolution, biotechnology, and public health. To reproduce and grow, microbes need to take up essential nutrients from the environment, and mathematical models classically assume that the nutrient uptake rate is a saturating function of the nutrient concentration. In nature, microbes experience different levels of nutrient availability at all environmental scales, yet parameters shaping the nutrient uptake function are commonly estimated for a single initial nutrient concentration. This hampers the models from accurately capturing microbial dynamics when the environmental conditions change. To address this problem, we conduct growth experiments for a range of micro-organisms, including human fungal pathogens, baker's yeast, and common coliform bacteria, and uncover the following patterns. We observed that the maximal nutrient uptake rate and biomass yield were both decreasing functions of initial nutrient concentration. While a functional form for the relationship between biomass yield and initial nutrient concentration has been previously derived from first metabolic principles, here we also derive the form of the relationship between maximal nutrient uptake rate and initial nutrient concentration. Incorporating these two functions into a model of microbial growth allows for variable growth parameters and enables us to substantially improve predictions for microbial dynamics in a range of initial nutrient concentrations, compared to keeping growth parameters fixed.


Assuntos
Candida , Enterobacteriaceae , Modelos Biológicos , Saccharomyces cerevisiae , Biotecnologia , Candida/citologia , Candida/crescimento & desenvolvimento , Candida/fisiologia , Proliferação de Células/fisiologia , Biologia Computacional , Ecologia , Enterobacteriaceae/citologia , Enterobacteriaceae/crescimento & desenvolvimento , Enterobacteriaceae/fisiologia , Saccharomyces cerevisiae/citologia , Saccharomyces cerevisiae/crescimento & desenvolvimento , Saccharomyces cerevisiae/fisiologia
8.
Eur J Med Chem ; 216: 113337, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33713977

RESUMO

A series of selenium-containing miconazole derivatives were identified as potent antifungal drugs in our previous study. Representative compound A03 (MIC = 0.01 µg/mL against C.alb. 5314) proved efficacious in inhibiting the growth of fungal pathogens. However, further study showed lead compound A03 exhibited potential hemolysis, significant cytotoxic effect and unfavorable metabolic stability and was therefore modified to overcome these drawbacks. In this article, the further optimization of selenium-containing miconazole derivatives resulted in the discovery of similarly potent compound B17 (MIC = 0.02 µg/mL against C.alb. 5314), exhibiting a superior pharmacological profile with decreased rate of metabolism, cytotoxic effect and hemolysis. Furthermore, compound B17 showed fungicidal activity against Candida albicans and significant effects on the treatment of resistant Candida albicans infections. Meanwhile, compound B17 not only could reduce the ergosterol biosynthesis pathway by inhibiting CYP51, but also inhibited biofilm formation. More importantly, compound B17 also shows promising in vivo efficacy after intraperitoneal injection and the PK study of compound B17 was evaluated. In addition, molecular docking studies provide a model for the interaction between the compound B17 and the CYP51 protein. Overall, we believe that these selenium-containing miconazole compounds can be further developed for the potential treatment of fungal infections.


Assuntos
Inibidores de 14-alfa Desmetilase/química , Antifúngicos/química , Miconazol/química , Selênio/química , Esterol 14-Desmetilase/química , Inibidores de 14-alfa Desmetilase/metabolismo , Inibidores de 14-alfa Desmetilase/farmacologia , Inibidores de 14-alfa Desmetilase/uso terapêutico , Animais , Antifúngicos/metabolismo , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Sítios de Ligação , Biofilmes/efeitos dos fármacos , Candida/efeitos dos fármacos , Candida/fisiologia , Candidíase/tratamento farmacológico , Candidíase/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Desenho de Fármacos , Meia-Vida , Humanos , Camundongos , Miconazol/metabolismo , Miconazol/farmacologia , Miconazol/uso terapêutico , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Esterol 14-Desmetilase/metabolismo , Relação Estrutura-Atividade
9.
Int Microbiol ; 24(2): 251-262, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33604754

RESUMO

Candida species are opportunistic fungi that can cause mucosal or invasive infections. Especially in biofilm-related infections, resistance is very high to anifungals; therefore more effective treatment strategies are needed. Farnesol(3,7,11-trimethyl-2,6,10-dodecatriene-1-ol) is the quorum sensing (QS) signal molecule and can interact with Candida species both as a QS molecule and as an exogenous agent. The aim of this study was to investigate the effects of farnesol on both the planktonic and biofilm forms of Candida species by colorimetric, microbiological, and electron microscopic methods. Obtained results demonstrated the inhibitory effect of farnesol on the planktonic and biofilm forms of Candida. Farnesol showed a biofilm-enhancing effect at lower concentrations. TEM findings showed the membrane and wall damage, vacuolization, or granulation in cells. SEM images confirmed biofilm reduction in pre-/post-biofilm applications as a result of farnesol treatment. In conclusion, farnesol can be used as an alternative agent to reduce the Candida biofilms, with future studies.


Assuntos
Antifúngicos/farmacologia , Biofilmes/efeitos dos fármacos , Candida/efeitos dos fármacos , Farneseno Álcool/farmacologia , Candida/classificação , Candida/crescimento & desenvolvimento , Candida/fisiologia , Candida albicans/efeitos dos fármacos , Candidíase/microbiologia , Humanos , Testes de Sensibilidade Microbiana
10.
J Med Microbiol ; 70(3)2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33599604

RESUMO

Over a decade ago, a multidrug-resistant nosocomial fungus Candida auris emerged worldwide and has since become a significant challenge for clinicians and microbiologists across the globe. A resilient pathogen, C. auris survives harsh disinfectants, desiccation and high-saline environments. It readily colonizes the inanimate environment, susceptible patients and causes invasive infections that exact a high toll. Prone to misidentification by conventional microbiology techniques, C. auris rapidly acquires multiple genetic determinants that confer multidrug resistance. Whole-genome sequencing has identified four distinct clades of C. auris, and possibly a fifth one, in circulation. Even as our understanding of this formidable pathogen grows, the nearly simultaneous emergence of its distinct clades in different parts of the world, followed by their rapid global spread, remains largely unexplained. We contend that certain host-pathogen-environmental factors have been evolving along adverse trajectories for the last few decades, especially in regions where C. auris originally appeared, until these factors possibly reached a tipping point to compel the evolution, emergence and spread of C. auris. Comparative genomics has helped identify several resistance mechanisms in C. auris that are analogous to those seen in other Candida species, but they fail to fully explain how high-level resistance rapidly develops in this yeast. A better understanding of these unresolved aspects is essential not only for the effective management of C. auris patients, hospital outbreaks and its global spread but also for forecasting and tackling novel resistant pathogens that might emerge in the future. In this review, we discuss the emergence, spread and resistance of C. auris, and propose future investigations to tackle this resilient pathogen.


Assuntos
Candida/fisiologia , Candidíase/microbiologia , Doenças Transmissíveis Emergentes/microbiologia , Farmacorresistência Fúngica Múltipla , Microbiologia Ambiental , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Candida/classificação , Candida/isolamento & purificação , Candida/patogenicidade , Candidíase/epidemiologia , Candidíase/transmissão , Doenças Transmissíveis Emergentes/epidemiologia , Doenças Transmissíveis Emergentes/transmissão , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Infecção Hospitalar/transmissão , Saúde Global , Humanos , Virulência
11.
J Clin Lab Anal ; 35(4): e23738, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33608902

RESUMO

BACKGROUND: To compare the adhesion properties and biofilm-forming capabilities of 27 Candida isolates obtained from catheter-related candidemia patients and to evaluate the inhibitory effects of antifungal agents on different Candida species. MATERIAL AND METHODS: Seven C. albicans, six C. parapsilosis, five C. guilliermondii, five C. tropicalis, and four C. glabrata clinical isolates were investigated. We quantified the adherence of these Candida species by flow cytometric method and evaluated the formation of biofilms by XTT reduction and crystal violet methods. Actions of micafungin (MF), fluconazole (FZ), and N-acetylcysteine (NAC) on the adhesion and biofilm formation of different Candida species were determined. RESULTS: Non-albicans Candida species were demonstrated to have stronger adhesion abilities compared with C. albicans. The biofilm-forming capabilities of different Candida species were varied considerably, and the degree of biofilm formation might be affected by different assay approaches. Interestingly, C. parapsilosis displayed the highest biofilm formation abilities, while C. glabrata exhibited the lowest total biomass and metabolic activity. Furthermore, the inhibitory activities of MF, FZ, and NAC on fungal adhesion and biofilm formation were evaluated, and the results indicated that MF could reduce the adhesion ability and biofilm metabolism more significantly (p < 0.05), and its antifungal activity was elevated in a dose-dependent manner. CONCLUSION: Non-albicans Candida species, especially C. guilliermondii, C. tropicalis, and C. parapsilosis, exhibited higher adhesion ability in catheter-related candidemia patients. However, these Candida species had varied biofilm-forming capabilities. MF tended to have stronger inhibitory effects against both adhesion and biofilm formation of different Candida species.


Assuntos
Antifúngicos/farmacologia , Candida , Candidemia/microbiologia , Infecções Relacionadas a Cateter/microbiologia , Adesão Celular/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Candida/efeitos dos fármacos , Candida/patogenicidade , Candida/fisiologia , Humanos
12.
Int J Mol Sci ; 22(2)2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33466640

RESUMO

Candida auris is a potential multidrug-resistant pathogen able to persist on indwelling devices as a biofilm, which serve as a source of catheter-associated infections. Neosartorya fischeri antifungal protein 2 (NFAP2) is a cysteine-rich, cationic protein with potent anti-Candida activity. We studied the in vitro activity of NFAP2 alone and in combination with fluconazole, amphotericin B, anidulafungin, caspofungin, and micafungin against C. auris biofilms. The nature of interactions was assessed utilizing the fractional inhibitory concentration index (FICI), a Bliss independence model, and LIVE/DEAD viability assay. NFAP2 exerted synergy with all tested antifungals with FICIs ranging between 0.312-0.5, 0.155-0.5, 0.037-0.375, 0.064-0.375, and 0.064-0.375 for fluconazole, amphotericin B, anidulafungin, caspofungin, and micafungin, respectively. These results were confirmed using a Bliss model, where NFAP2 produced 17.54 µM2%, 2.16 µM2%, 33.31 µM2%, 10.72 µM2%, and 111.19 µM2% cumulative synergy log volume in combination with fluconazole, amphotericin B, anidulafungin, caspofungin, and micafungin, respectively. In addition, biofilms exposed to echinocandins (32 mg/L) showed significant cell death in the presence of NFAP2 (128 mg/L). Our study shows that NFAP2 displays strong potential as a novel antifungal compound in alternative therapies to combat C. auris biofilms.


Assuntos
Antifúngicos/metabolismo , Biofilmes/efeitos dos fármacos , Candida/efeitos dos fármacos , Proteínas Fúngicas/metabolismo , Neosartorya/metabolismo , Antifúngicos/farmacologia , Candida/fisiologia , Candidíase/tratamento farmacológico , Candidíase/microbiologia , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Sinergismo Farmacológico , Proteínas Fúngicas/farmacologia , Humanos
13.
J Appl Microbiol ; 130(4): 1142-1153, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32981148

RESUMO

AIMS: This study aimed to assess the antifungal and anti-biofilm effects of 6-shogaol against Candida auris using in vitro phenotypic and genotypic analyses. METHODS AND RESULTS: Our results showed that 6-shogaol exhibited antifungal as well as anti-biofilm activity by inhibiting biofilm formation and eradicating the preformed biofilms of C. auris. The rate and extent of antifungal activity were further confirmed by a time-kill assay. The XTT reduction assay confirmed that 6-shogaol decreased cellular metabolic activity in the biofilm. The effect of 6-shogaol on established C. auris biofilms was visualized by confocal laser scanning microscopy. Also, this study demonstrated that 6-shogaol reduced the levels of aspartyl proteinases and downregulated the expression of the efflux pump-related CDR1 gene in C. auris. CONCLUSIONS: The data indicated that 6-shogaol extracted from ginger had antifungal and anti-biofilm effects on C. auris. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrated the value of the plant-derived 6-shogaol as a promising and potent bioactive compound. The mode of action of this compound against C. auris biofilm was also proposed.


Assuntos
Antifúngicos/farmacologia , Biofilmes/efeitos dos fármacos , Candida/efeitos dos fármacos , Catecóis/farmacologia , Ácido Aspártico Proteases/genética , Ácido Aspártico Proteases/metabolismo , Biofilmes/crescimento & desenvolvimento , Candida/fisiologia , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos
14.
Lett Appl Microbiol ; 72(1): 82-89, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32978979

RESUMO

Candida auris is an emerging species responsible for life-threatening infections. Its ability to be resistant to most systemic antifungal classes and its capacity to persist in a hospital environment have led to health concerns. Currently, data about environmental reservoirs are limited but remain essential in control of C. auris spread. The aim of our study was to explore the interactions between C. auris and two free-living amoeba (FLA) species, Vermamoeba vermiformis and Acanthamoeba castellanii, potentially found in the same water environment. Candida auris was incubated with FLA trophozoites or their culture supernatants. The number of FLA and yeasts was determined at different times and transmission electron microscopy (TEM) was performed. Supernatants of FLAs promoted yeast survival and proliferation. Internalization of viable C. auris within both FLA species was also evidenced by TEM. A water environmental reservoir of C. auris can therefore be considered through FLAs and contamination of the hospital water networks would consequently be possible.


Assuntos
Amoeba/fisiologia , Candida/fisiologia , Microbiologia da Água , Candida/crescimento & desenvolvimento , Candida albicans/fisiologia , Proliferação de Células
15.
Mycoses ; 64(2): 152-156, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33275821

RESUMO

BACKGROUND: The incidence of candidemia in our hospital has been stable over an 18-year period (1.3 episodes per 1000 admissions). Since March 2020, we have observed an increase in cases of candidemia. METHODS: In March 2020, the hospital was prepared to receive patients with COVID-19, with cancellation of elective procedures, discharge of less sick patients and the activation of beds for COVID-19. We compared the incidence of candidemia in 2 periods: from January 2019 to February 2020 (period 1) and from March to September 2020 (period 2). RESULTS: We diagnosed 41 episodes of candidemia, 16 in period 1 and 25 in period 2 (9 COVID-19 patients). Compared with non-COVID-19 patients, COVID-19 patients with candidemia were more likely to be under mechanical ventilation (100% vs. 34.4%, P < .001). The median number of monthly admissions in period 1 and 2 was 723 (interquartile range 655-836) and 523 (interquartile range 389-574), respectively. The incidence of candidemia (per 1000 admissions) was 1.54 in period 1 and 7.44 in period 2 (P < .001). In period 2, the incidence of candidemia (per 1000 admissions) was 4.76 if we consider only cases of candidemia in non-COVID-19 patients, 2.68 if we consider only cases of candidemia in COVID-19 patients and 14.80 considering only admissions of patients with COVID-19. CONCLUSIONS: The increase in the incidence of candidemia in our hospital may be attributed to 2 factors: a reduction in the number of admissions (denominator) and the occurrence of candidemia in COVID-19 patients.


Assuntos
COVID-19/complicações , Candidemia/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , COVID-19/epidemiologia , COVID-19/virologia , Candida/genética , Candida/isolamento & purificação , Candida/fisiologia , Candidemia/epidemiologia , Candidemia/microbiologia , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , SARS-CoV-2/fisiologia , Centros de Atenção Terciária/estatística & dados numéricos , Adulto Jovem
16.
J Clin Invest ; 131(5)2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33373326

RESUMO

The emergence of drug-resistant fungi has prompted an urgent threat alert from the US Centers for Disease Control (CDC). Biofilm assembly by these pathogens further impairs effective therapy. We recently identified an antifungal, turbinmicin, that inhibits the fungal vesicle-mediated trafficking pathway and demonstrates broad-spectrum activity against planktonically growing fungi. During biofilm growth, vesicles with unique features play a critical role in the delivery of biofilm extracellular matrix components. As these components are largely responsible for the drug resistance associated with biofilm growth, we explored the utility of turbinmicin in the biofilm setting. We found that turbinmicin disrupted extracellular vesicle (EV) delivery during biofilm growth and that this impaired the subsequent assembly of the biofilm matrix. We demonstrated that elimination of the extracellular matrix rendered the drug-resistant biofilm communities susceptible to fungal killing by turbinmicin. Furthermore, the addition of turbinmicin to otherwise ineffective antifungal therapy potentiated the activity of these drugs. The underlying role of vesicles explains this dramatic activity and was supported by phenotype reversal with the addition of exogenous biofilm EVs. This striking capacity to cripple biofilm assembly mechanisms reveals a new approach to eradicating biofilms and sheds light on turbinmicin as a promising anti-biofilm drug.


Assuntos
Benzopiranos/farmacologia , Biofilmes/efeitos dos fármacos , Candida/fisiologia , Vesículas Extracelulares/metabolismo , Isoquinolinas/farmacologia , Biofilmes/crescimento & desenvolvimento
17.
PLoS One ; 15(12): e0243223, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33264362

RESUMO

BACKGROUND: Candida auris infections have recently emerged worldwide, and this species is highly capable of colonization and is associated with high levels of mortality. However, strain-dependent differences in colonization capabilities and virulence have not yet been reported. OBJECTIVES: In the present study, we aimed to clarify the differences between clinically isolated invasive and non-invasive strains of C. auris. METHODS: We evaluated colonization, dissemination, and survival rates in wild C57BL/6J mice inoculated with invasive or non-invasive strains of C. auris under cortisone acetate immunosuppression, comparing with those of Candida albicans and Candida glabrata infections. We also evaluated the potency of biofilm formation. RESULTS: Stool fungal burdens were significantly higher in mice inoculated with the invasive strains than in those infected with the non-invasive strain. Along with intestinal colonization, liver and kidney fungal burdens were also significantly higher in mice inoculated with the invasive strains. In addition, histopathological findings revealed greater dissemination and colonization of the invasive strains. Regarding biofilm-forming capability, the invasive strain of C. auris exhibited a significantly higher capacity of producing biofilms. Moreover, inoculation with the invasive strains resulted in significantly greater loss of body weight than that noted following infection with the non-invasive strain. CONCLUSIONS: Invasive strains showed higher colonization capability and rates of dissemination from gastrointestinal tracts under cortisone acetate immunosuppression than non-invasive strains, although the mortality rates caused by C. auris were lower than those caused by C. albicans.


Assuntos
Candida/fisiologia , Candidíase Invasiva/patologia , Candidíase/patologia , Trato Gastrointestinal/microbiologia , Animais , Biofilmes/crescimento & desenvolvimento , Candida/patogenicidade , Candida albicans/patogenicidade , Candida albicans/fisiologia , Candida glabrata/patogenicidade , Candida glabrata/fisiologia , Candidíase/microbiologia , Candidíase Invasiva/microbiologia , Trato Gastrointestinal/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Virulência
18.
mBio ; 11(6)2020 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-33323512

RESUMO

Candida auris has emerged as a serious threat to the health care settings. Advancements in molecular biology have provided several insights into the evolution of C. auris since it was first described in 2009. However, the simultaneous emergence of four different clades of the fungus at distinct geographical locations remains a mystery. The hypotheses already proposed by researchers fall short of explaining how and why C. auris emerged. In this article, we theorize that C. auris emerged from a common ancestor, subsequently migrated to specific geographical locations, and diversified genetically. This hypothesis is supported by genomic insights, historical events, and indirect scientific facts. C. auris adapted to humans at locations and times coinciding with the divergence from the most recent common ancestor, emerging almost simultaneously as an opportunist pathogen due to antiseptic practices. Future research will support or refute this hypothesis.


Assuntos
Anti-Infecciosos Locais/farmacologia , Evolução Biológica , Candida/efeitos dos fármacos , Candida/genética , Ecossistema , Candida/classificação , Candida/fisiologia , Candidíase/microbiologia , Meio Ambiente , Humanos , Modelos Biológicos , Filogenia , Estresse Fisiológico
19.
Molecules ; 25(24)2020 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-33339401

RESUMO

OBJECTIVE: This study evaluated the antifungal activity of cinnamaldehyde on Candida spp. In vitro and in situ assays were carried out to test cinnamaldehyde for its anti-Candida effects, antibiofilm activity, effects on fungal micromorphology, antioxidant activity, and toxicity on keratinocytes and human erythrocytes. Statistical analysis was performed considering α = 5%. RESULTS: The minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of cinnamaldehyde ranged from 18.91 µM to 37.83 µM. MIC values did not change in the presence of 0.8 M sorbitol, whereas an 8-fold increase was observed in the presence of ergosterol, suggesting that cinnamaldehyde may act on the cell membrane, which was subsequently confirmed by docking analysis. The action of cinnamaldehyde likely includes binding to enzymes involved in the formation of the cytoplasmic membrane in yeast cells. Cinnamaldehyde-treated microcultures showed impaired cellular development, with an expression of rare pseudo-hyphae and absence of chlamydoconidia. Cinnamaldehyde reduced biofilm adherence by 64.52% to 33.75% (p < 0.0001) at low concentrations (378.3-151.3 µM). Cinnamaldehyde did not show antioxidant properties. CONCLUSIONS: Cinnamaldehyde showed fungicidal activity through a mechanism of action likely related to ergosterol complexation; it was non-cytotoxic to keratinocytes and human erythrocytes and showed no antioxidant activity.


Assuntos
Acroleína/análogos & derivados , Antifúngicos/farmacologia , Biofilmes/efeitos dos fármacos , Candida/fisiologia , Acroleína/química , Acroleína/metabolismo , Acroleína/farmacologia , Antifúngicos/química , Antifúngicos/metabolismo , Antioxidantes/química , Sítios de Ligação , Candida/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Ergosterol/química , Ergosterol/farmacologia , Humanos , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Sorbitol/química , Sorbitol/farmacologia , Esqualeno Mono-Oxigenase/química , Esqualeno Mono-Oxigenase/metabolismo
20.
PLoS Pathog ; 16(12): e1009094, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33332439
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