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1.
Curr Protoc ; 1(7): e194, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34242490

RESUMO

Candida albicans biofilm formation in the presence of drugs can be examined through time-lapse microscopy. In many cases, the images are used qualitatively, which limits their utility for hypothesis testing. We employed a machine-learning algorithm implemented in the Orbit Image Analysis program to detect the percent area covered by cells from each image. This is combined with custom R scripts to determine the growth rate, growth asymptote, and time to reach the asymptote as quantitative proxies for biofilm formation. We describe step-by-step protocols that go from sample preparation for time-lapse microscopy through image analysis parameterization and visualization of the model fit. © 2021 Wiley Periodicals LLC. Basic Protocol 1: Sample preparation Basic Protocol 2: Time-lapse microscopy: Evos protocol Basic Protocol 3: Batch file renaming Basic Protocol 4: Machine learning analysis of Evos images with Orbit Basic Protocol 5: Parametrization of Orbit output in R Basic Protocol 6: Visualization of logistic fits in R.


Assuntos
Candida albicans , Microscopia , Biofilmes , Processamento de Imagem Assistida por Computador , Imagem com Lapso de Tempo
2.
Front Cell Infect Microbiol ; 11: 648988, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34222036

RESUMO

Immune cells can optimize the management of metabolic resources to balance their energy requirements in order to regulate immune responses. The interconnection between immunometabolism and fungal infections is becoming increasingly apparent. Using proteome and metabolome assays, we found that stimulation of primary human monocytes by Candida albicans was accompanied by upregulation of glucose transporter 3 (GLUT3) and activation of the glycerophospholipid metabolism pathway. Upregulated GLUT3 expression has been preliminarily confirmed in monocytes from patients with C. albicans bloodstream infection. Our findings support the importance of GLUT3 in the complex network of glycerophospholipid metabolism and the innate immune responses against C. albicans. In summary, this study might contribute to decipher the regulatory mechanism between the monocyte metabolic reprogramming and innate immune response and reveal potential targets for the antifungal treatments.


Assuntos
Candida albicans , Imunidade Inata , Glicerofosfolipídeos , Humanos , Metabolismo dos Lipídeos , Monócitos
3.
Molecules ; 26(12)2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34200763

RESUMO

The development of new antimicrobial strategies that act more efficiently than traditional antibiotics is becoming a necessity to combat multidrug-resistant pathogens. Here we report the efficacy of laser-light-irradiated 5,10,15,20-tetrakis(m-hydroxyphenyl)porphyrin (mTHPP) loaded onto an ethylcellulose (EC)/chitosan (Chs) nanocomposite in eradicating multi-drug resistant Pseudomonas aeruginosa, Staphylococcus aureus, and Candida albicans. Surface loading of the ethylcelllose/chitosan composite with mTHPP was carried out and the resulting nanocomposite was fully characterized. The results indicate that the prepared nanocomposite incorporates mTHPP inside, and that the composite acquired an overall positive charge. The incorporation of mTHPP into the nanocomposite enhanced the photo- and thermal stability. Different laser wavelengths (458; 476; 488; 515; 635 nm), powers (5-70 mW), and exposure times (15-45 min) were investigated in the antimicrobial photodynamic therapy (aPDT) experiments, with the best inhibition observed using 635 nm with the mTHPP EC/Chs nanocomposite for C. albicans (59 ± 0.21%), P. aeruginosa (71.7 ± 1.72%), and S. aureus (74.2 ± 1.26%) with illumination of only 15 min. Utilization of higher doses (70 mW) for longer periods achieved more eradication of microbial growth.


Assuntos
Antibacterianos/química , Celulose/análogos & derivados , Quitosana/química , Nanocompostos/química , Porfirinas/química , Piridonas/química , Pirróis/química , Animais , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Linhagem Celular , Celulose/química , Chlorocebus aethiops , Lasers , Luz , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Células Vero
4.
BMJ Case Rep ; 14(6)2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: covidwho-1282060

RESUMO

An 81-year-old man was referred to the colorectal surgeons for an elective laparoscopic right hemicolectomy for a caecal adenocarcinoma (T2N0M0). The operation was uneventful; however, 12 days postoperatively the patient developed symptoms of sepsis of unknown origin. After extensive investigations and work up, Candida albicans was grown as the causative organism with the site of infection being a new saccular mycotic aneurysm arising from the distal, posterior aspect of the aortic arch. The mycotic aneurysm was not initially considered as a differential diagnosis, and this case highlights the importance of consideration of mycotic aneurysm as a differential diagnosis in postsurgical septic patients.


Assuntos
Aneurisma Infectado , Neoplasias do Colo , Laparoscopia , Idoso de 80 Anos ou mais , Aneurisma Infectado/diagnóstico por imagem , Aneurisma Infectado/cirurgia , Aorta Torácica , Candida albicans , Colectomia , Neoplasias do Colo/cirurgia , Humanos , Masculino
5.
Biomolecules ; 11(5)2021 05 17.
Artigo em Inglês | MEDLINE | ID: covidwho-1234665

RESUMO

Cm-p5 is a snail-derived antimicrobial peptide, which demonstrated antifungal activity against the pathogenic strains of Candida albicans. Previously we synthetized a cyclic monomer as well as a parallel and an antiparallel dimer of Cm-p5 with improved antifungal activity. Considering the alarming increase of microbial resistance to conventional antibiotics, here we evaluated the antimicrobial activity of these derivatives against multiresistant and problematic bacteria and against important viral agents. The three peptides showed a moderate activity against Pseudomonas aeruginosa, Klebsiella pneumoniae Extended Spectrum ß-Lactamase (ESBL), and Streptococcus agalactiae, with MIC values > 100 µg/mL. They exerted a considerable activity with MIC values between 25-50 µg/mL against Acinetobacter baumanii and Enterococcus faecium. In addition, the two dimers showed a moderate activity against Pseudomonas aeruginosa PA14. The three Cm-p5 derivatives inhibited a virulent extracellular strain of Mycobacterium tuberculosis, in a dose-dependent manner. Moreover, they inhibited Herpes Simplex Virus 2 (HSV-2) infection in a concentration-dependent manner, but had no effect on infection by the Zika Virus (ZIKV) or pseudoparticles of Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2). At concentrations of >100 µg/mL, the three new Cm-p5 derivatives showed toxicity on different eukaryotic cells tested. Considering a certain cell toxicity but a potential interesting activity against the multiresistant strains of bacteria and HSV-2, our compounds require future structural optimization.


Assuntos
Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/química , Antivirais/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Herpesvirus Humano 2/efeitos dos fármacos , Sequência de Aminoácidos , Animais , Antibacterianos/química , Peptídeos Catiônicos Antimicrobianos/farmacologia , Antivirais/química , Candida albicans/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Dimerização , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , SARS-CoV-2/efeitos dos fármacos
6.
Molecules ; 26(9)2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-34066433

RESUMO

Candida albicans, an opportunistic fungal pathogen, frequently colonizes immune-compromised patients and causes mild to severe systemic reactions. Only few antifungal drugs are currently in use for therapeutic treatment. However, evolution of a drug-resistant C. albicans fungal pathogen is of major concern in the treatment of patients, hence the clinical need for novel drug design and development. In this study, in vitro screening of novel putative pyrrolo[1,2-a]quinoline derivatives as the lead drug targets and in silico prediction of the binding potential of these lead molecules against C. albicans pathogenic proteins, such as secreted aspartic protease 3 (SAP3; 2H6T), surface protein ß-glucanase (3N9K) and sterol 14-alpha demethylase (5TZ1), were carried out by molecular docking analyses. Further, biological activity-based QSAR and theoretical pharmacokinetic analysis were analyzed. Here, in vitro screening of novel analogue derivatives as drug targets against C. albicans showed inhibitory potential in the concentration of 0.4 µg for BQ-06, 07 and 08, 0.8 µg for BQ-01, 03, and 05, 1.6 µg for BQ-04 and 12.5 µg for BQ-02 in comparison to the standard antifungal drug fluconazole in the concentration of 30 µg. Further, in silico analysis of BQ-01, 03, 05 and 07 analogues docked on chimeric 2H6T, 3N9K and 5TZ1 revealed that these analogues show potential binding affinity, which is different from the therapeutic antifungal drug fluconazole. In addition, these molecules possess good drug-like properties based on the determination of conceptual Density Functional Theory (DFT)-based descriptors, QSAR and pharmacokinetics. Thus, the study offers significant insight into employing pyrrolo[1,2-a]quinoline analogues as novel antifungal agents against C. albicans that warrants further investigation.


Assuntos
Antifúngicos/síntese química , Ácidos Carboxílicos/síntese química , Teoria da Densidade Funcional , Simulação de Acoplamento Molecular , Antifúngicos/farmacocinética , Candida albicans , Ácidos Carboxílicos/farmacocinética , Química Farmacêutica/métodos , Desenho de Fármacos , Fluconazol/farmacologia , Ligação de Hidrogênio , Indolizinas/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Conformação Proteica , Relação Quantitativa Estrutura-Atividade , Quinolinas/síntese química , Quinolinas/farmacocinética , Termodinâmica
7.
BMJ Case Rep ; 14(6)2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34167978

RESUMO

An 81-year-old man was referred to the colorectal surgeons for an elective laparoscopic right hemicolectomy for a caecal adenocarcinoma (T2N0M0). The operation was uneventful; however, 12 days postoperatively the patient developed symptoms of sepsis of unknown origin. After extensive investigations and work up, Candida albicans was grown as the causative organism with the site of infection being a new saccular mycotic aneurysm arising from the distal, posterior aspect of the aortic arch. The mycotic aneurysm was not initially considered as a differential diagnosis, and this case highlights the importance of consideration of mycotic aneurysm as a differential diagnosis in postsurgical septic patients.


Assuntos
Aneurisma Infectado , Neoplasias do Colo , Laparoscopia , Idoso de 80 Anos ou mais , Aneurisma Infectado/diagnóstico por imagem , Aneurisma Infectado/cirurgia , Aorta Torácica , Candida albicans , Colectomia , Neoplasias do Colo/cirurgia , Humanos , Masculino
8.
Nat Commun ; 12(1): 3899, 2021 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-34162849

RESUMO

The ability of the fungal pathogen Candida albicans to undergo a yeast-to-hypha transition is believed to be a key virulence factor, as filaments mediate tissue damage. Here, we show that virulence is not necessarily reduced in filament-deficient strains, and the results depend on the infection model used. We generate a filament-deficient strain by deletion or repression of EED1 (known to be required for maintenance of hyphal growth). Consistent with previous studies, the strain is attenuated in damaging epithelial cells and macrophages in vitro and in a mouse model of intraperitoneal infection. However, in a mouse model of systemic infection, the strain is as virulent as the wild type when mice are challenged with intermediate infectious doses, and even more virulent when using low infectious doses. Retained virulence is associated with rapid yeast proliferation, likely the result of metabolic adaptation and improved fitness, leading to high organ fungal loads. Analyses of cytokine responses in vitro and in vivo, as well as systemic infections in immunosuppressed mice, suggest that differences in immunopathology contribute to some extent to retained virulence of the filament-deficient mutant. Our findings challenge the long-standing hypothesis that hyphae are essential for pathogenesis of systemic candidiasis by C. albicans.


Assuntos
Candida albicans/metabolismo , Candidíase/metabolismo , Proteínas Fúngicas/metabolismo , Hifas/metabolismo , Animais , Candida albicans/genética , Candida albicans/patogenicidade , Candidíase/microbiologia , Divisão Celular/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Proteínas Fúngicas/genética , Regulação Fúngica da Expressão Gênica , Humanos , Hifas/genética , Hifas/crescimento & desenvolvimento , Macrófagos/metabolismo , Camundongos Endogâmicos BALB C , Mutação , Neutrófilos/metabolismo , Virulência/genética
9.
Shanghai Kou Qiang Yi Xue ; 30(2): 156-161, 2021 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-34109354

RESUMO

PURPOSE: To investigate the relationship between oral Candida albicans and flora in children with severe infant caries. METHODS: Forty-two children with severe infant caries (experimental group) and 40 caries-free children (control group) treated in Peking University Shenzhen Hospital from March 2018 to June 2019 were enrolled. The samples of saliva and plaque were collected and cultured. According to the culture results, the experimental group was further divided into two subgroups: Candida albicans positive group and Candida albicans negative group. The samples were sequenced by high-throughput sequencing technology, then the diversity and abundance of bacteria were analyzed. The data were processed by SPSS 23.0 software package. RESULTS: The positive rates of Candida albicans in saliva and plaque were significantly higher in the experimental group than in the control group(P<0.05). The abundance of Leptotrichia and Cardiobacterium in the saliva of children with positive Candida albicans in the experimental group was significantly higher than that of children with negative Candida albicans(P<0.05). The abundance of Prevotella in plaque of children with positive Candida albicans in the experimental group was significantly higher than that of children with negative Candida albicans and control group(P<0.05). The abundance of Leptotrichia in saliva of children with positive Candida albicans in the experimental group was significantly higher than that of children with negative Candida albicans (P<0.05), while the abundances of Capnocytophaga, Cardiobacterium hominis, and Capnocytophaga granulose were significantly lower than those of children with negative Candida albicans(P<0.05). The abundance of Streptococcus mutans, Lactobacillus gasseri, and Lactobacillus vaginalis in the plaque of positive Candida albicans in the experimental group were significantly higher than those of children with negative Candida albicans(P<0.05), while the abundance of Lactobacillus plantarum was significantly lower than that of children with negative Candida albicans (P<0.05). CONCLUSIONS: Candida albicans in children with severe infant caries children is closely correlated with the abundance of Leptotrichia, Capnocytophaga, Cardiobacterium hominis, Capnocytophaga granulosa, Streptococcus mutans and Lactobacillus, which may play a synergistic or antagonistic role.


Assuntos
Candida albicans , Cárie Dentária , Capnocytophaga , Cardiobacterium , Criança , Pré-Escolar , Suscetibilidade à Cárie Dentária , Humanos , Lactente , Lactobacillus , Saliva , Streptococcus mutans
10.
BMC Infect Dis ; 21(1): 523, 2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-34082699

RESUMO

BACKGROUND: Vaginal candidiasis is frequent in women of reproductive age. Accurate identification Candida provides helpful information for successful therapy and epidemiology study; however, there are very limited data from the Vietnam have been reported. This study was performed to determine the prevalence, species distribution of yeast causing vaginal discharge and antifungal susceptibility patterns of Candida albicans among symptomatic non-pregnant women of reproductive age. METHODS: Vaginal discharge samples were collected from 462 women of reproductive age in Hanoi, Vietnam between Sep 2019 and Oct 2020. Vaginal swabs from these patients were examined by direct microscopic examination (10% KOH). CHROMagar™ Candida medium and Sabouraud dextrose agar supplemented with chloramphenicol (0.5 g/l) were used to isolate yeast, and species identification was performed using morphological tests and molecular tools (PCR and sequencing). Antifungal susceptibility testing was determined according to the Clinical and Laboratory Standards Institute guidelines (M27-A3 and M27-S4). RESULTS: The prevalence of vaginal yeast colonization in non-pregnant women was 51.3% of 462 participants. Nine different yeast species were identified. Among these isolates, C. albicans (51.37%) was the most frequent, followed by C. parapsilosis (25.88%), C. glabrata (11.37%), C. tropicalis (4.31%), C. krusei (3.92%), C. africana (1.57%), Saccharomyces cerevisiae (0.78%), C. nivariensis (1 isolates, 0.39%), and C. lusitaniae (1 isolates, 0.39%), respectively. Among C. albicans, all 46 isolates were 100% susceptible to micafungin, caspofungin, and miconazole. The susceptibility rates to amphotericine B, 5-flucytosine, fluconazole, itraconazole and voriconazole were 95.65, 91.30, 91.30, 82.61 and 86.95%, respectively. CONCLUSIONS: The prevalence of VVC among symptomatic non-pregnant women of reproductive age in Vietnam was higher than many parts of the world. The high frequency of non-albicans Candida species, which were often more resistant to antifungal agents, was a notable feature. Resistance rates of vaginal C. albicans isolates to antifungal agents was low. Our findings suggest that continued surveillance of changes in species distribution and susceptibility to antifungals should be routinely screened and treated.


Assuntos
Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Candidíase Vulvovaginal/microbiologia , Descarga Vaginal/microbiologia , Adolescente , Adulto , Candida/classificação , Candida/efeitos dos fármacos , Candida/isolamento & purificação , Candida albicans/classificação , Candida albicans/isolamento & purificação , Candidíase Vulvovaginal/epidemiologia , Farmacorresistência Fúngica/efeitos dos fármacos , Feminino , Humanos , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Prevalência , Centros de Atenção Terciária , Descarga Vaginal/epidemiologia , Vietnã/epidemiologia , Adulto Jovem
11.
Klin Lab Diagn ; 66(6): 358-363, 2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34105912

RESUMO

Histatins are the most significant antimicrobial peptides (AMP) of saliva and there are 12 types of such AMP. Histatin molecules contain relatively high percent of histidine and tyrosine residues. This property allows to use well known from organic chemistry Pauly reaction for detection of protein bounded histidine and tyrosine residues (BHT), which are in fact characterize the summary content of all histatins in saliva. Aim of the present study was comparison of BHT with antimicrobial activity of salivary AMP fraction in patients with inflammatory diseases of upper airways (IDUA). Group of examined persons include 28 patients with different diagnoses: chronic pharyngitis (n=11), chronic tonsillitis (n=7), nasopharyngitis (n=5), pollinosis (n=5). Degree of intensity of inflammatory symptoms was estimated in balls. The algorithm of BHT analysis include following steps: freezing - thawing of saliva; removal of microparticles by centrifugation; separation of fraction lower than100 kDa; dialysis for free amino acids removal; Pauly reaction carrying out. Antimicrobial activities of saliva and its low molecular fractions were estimated towards Candida albicans cells by the spectrophotometric method with bromocresol purpur. Analysis of saliva sediments for coccoid microbiota was carried out by PCR method. Pauly reaction for histatins estimation in saliva of IDUA patients use here for the first time. The histatins levels (BHT) were significantly correlated with the intensity of inflammatory symptoms (r=0,975) and activity of low molecular salivary fraction (AMP activity) (r=0,824). The AMP activity/ BHT ratio, i.e. antimicrobial activity of histatin unit, decreased together with growth of inflammatory symptoms intensity (r=-0,944). Any considerable differences in coccoid microbiota frequency of finding at different diagnoses were not detected. The S. aureus frequency of occurrence was connected neither with inflammatory symptoms intensity (r=0,118), nor with BHT concentration (r=0,318). However S. pyogenes and S. pneumoniae frequencies of occurrence demonstrated the invert correlation towards these indexes: (r=-0,627/-0,614) and (r=-0,827/-0,864). Probably at the exacerbation forms of IDUA the S. pyogenes and S. pneumoniae growth controlled by high levels of histatins.


Assuntos
Histatinas , Staphylococcus aureus , Sequência de Aminoácidos , Candida albicans , Humanos , Saliva , Proteínas e Peptídeos Salivares
12.
Int J Mol Sci ; 22(10)2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-34065835

RESUMO

The discovery of eco-friendly, rapid, and cost-effective compounds to control diseases caused by microbes and insects are the main challenges. Herein, the magnesium oxide nanoparticles (MgO-NPs) are successfully fabricated by harnessing the metabolites secreted by Penicillium chrysogenum. The fabricated MgO-NPs were characterized using UV-Vis, XRD, TEM, DLS, EDX, FT-IR, and XPS analyses. Data showed the successful formation of crystallographic, spherical, well-dispersed MgO-NPs with sizes of 7-40 nm at a maximum wavelength of 250 nm. The EDX analysis confirms the presence of Mg and O ions as the main components with weight percentages of 13.62% and 7.76%, respectively. The activity of MgO-NPs as an antimicrobial agent was investigated against pathogens Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, Escherichia coli, and Candida albicans, and exhibited zone of inhibitions of 12.0 ± 0.0, 12.7 ± 0.9, 23.3 ± 0.8, 17.7 ± 1.6, and 14.7 ± 0.6 mm respectively, at 200 µg mL-1. The activity is decreased by decreasing the MgO-NPs concentration. The biogenic MgO-NPs exhibit high efficacy against different larvae instar and pupa of Anopheles stephensi, with LC50 values of 12.5-15.5 ppm for I-IV larvae instar and 16.5 ppm for the pupa. Additionally, 5 mg/cm2 of MgO-NPs showed the highest protection percentages against adults of Anopheles stephensi, with values of 100% for 150 min and 67.6% ± 1.4% for 210 min.


Assuntos
Anopheles/efeitos dos fármacos , Anti-Infecciosos/farmacologia , Inseticidas/farmacologia , Óxido de Magnésio/farmacologia , Penicillium chrysogenum/crescimento & desenvolvimento , Animais , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Bacillus subtilis/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Cristalografia por Raios X , Escherichia coli/efeitos dos fármacos , Química Verde , Inseticidas/química , Inseticidas/isolamento & purificação , Larva/efeitos dos fármacos , Óxido de Magnésio/química , Óxido de Magnésio/isolamento & purificação , Metabolômica , Nanopartículas Metálicas/química , Nanopartículas Metálicas/ultraestrutura , Testes de Sensibilidade Microbiana , Tamanho da Partícula , Penicillium chrysogenum/química , Pseudomonas aeruginosa/efeitos dos fármacos , Pupa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos
13.
Int J Mol Sci ; 22(10)2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-34065861

RESUMO

Various peptides and their derivatives have been reported to exhibit antimicrobial activities. Although these activities have been examined against microorganisms, novel methods have recently emerged for conjugation of the biomaterials to improve their activities. Here, we prepared CKR12-PLGA, in which CKR12 (a mutated fragment of human cathelicidin peptide, LL-37) was conjugated with poly (lactic-co-glycolic) acid (PLGA), and compared the antimicrobial and antifungal activities of the conjugated peptide with those of FK13 (a small fragment of LL-37) and CKR12 alone. The prepared CKR12-PLGA was characterized by dynamic light scattering and measurement of the zeta potential, critical micellar concentration, and antimicrobial activities of the fragments and conjugate. Although CKR12 showed higher antibacterial activities than FK13 against Staphylococcus aureus and Escherichia coli, the antifungal activity of CKR12 was lower than that of FK13. CKR12-PLGA showed higher antibacterial activities against S. aureus and E. coli and higher antifungal activity against Candida albicans compared to those of FK13. Additionally, CKR12-PLGA showed no hemolytic activity in erythrocytes, and scanning and transmission electron microscopy suggested that CKR12-PLGA killed and disrupted the surface structure of microbial cells. Conjugation of antimicrobial peptide fragment analogues was a successful approach for obtaining increased microbial activity with minimized cytotoxicity.


Assuntos
Anti-Infecciosos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Anti-Infecciosos/química , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/genética , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Candida albicans/ultraestrutura , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Escherichia coli/ultraestrutura , Humanos , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Microscopia Eletrônica de Transmissão , Mutação , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Staphylococcus aureus/ultraestrutura
14.
Cell Host Microbe ; 29(6): 856-858, 2021 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-34111393

RESUMO

In this issue of Cell Host & Microbe, Witchley et al. (2021) describe a rewired transcriptional network that reveals how the human fungal pathogen Candida albicans favors commensalism over sexual reproduction in the host environment.


Assuntos
Candida albicans , Simbiose , Candida albicans/genética , Comunicação Celular , DNA , Humanos , Reprodução
15.
Biomolecules ; 11(5)2021 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-34067685

RESUMO

Cm-p5 is a snail-derived antimicrobial peptide, which demonstrated antifungal activity against the pathogenic strains of Candida albicans. Previously we synthetized a cyclic monomer as well as a parallel and an antiparallel dimer of Cm-p5 with improved antifungal activity. Considering the alarming increase of microbial resistance to conventional antibiotics, here we evaluated the antimicrobial activity of these derivatives against multiresistant and problematic bacteria and against important viral agents. The three peptides showed a moderate activity against Pseudomonas aeruginosa, Klebsiella pneumoniae Extended Spectrum ß-Lactamase (ESBL), and Streptococcus agalactiae, with MIC values > 100 µg/mL. They exerted a considerable activity with MIC values between 25-50 µg/mL against Acinetobacter baumanii and Enterococcus faecium. In addition, the two dimers showed a moderate activity against Pseudomonas aeruginosa PA14. The three Cm-p5 derivatives inhibited a virulent extracellular strain of Mycobacterium tuberculosis, in a dose-dependent manner. Moreover, they inhibited Herpes Simplex Virus 2 (HSV-2) infection in a concentration-dependent manner, but had no effect on infection by the Zika Virus (ZIKV) or pseudoparticles of Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2). At concentrations of >100 µg/mL, the three new Cm-p5 derivatives showed toxicity on different eukaryotic cells tested. Considering a certain cell toxicity but a potential interesting activity against the multiresistant strains of bacteria and HSV-2, our compounds require future structural optimization.


Assuntos
Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/química , Antivirais/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Herpesvirus Humano 2/efeitos dos fármacos , Sequência de Aminoácidos , Animais , Antibacterianos/química , Peptídeos Catiônicos Antimicrobianos/farmacologia , Antivirais/química , Candida albicans/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Dimerização , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , SARS-CoV-2/efeitos dos fármacos
16.
Int J Mol Sci ; 22(9)2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-34068595

RESUMO

Systemic inflammation, from gut translocation of organismal molecules, might worsen uremic complications in acute kidney injury (AKI). The monitoring of gut permeability integrity and/or organismal molecules in AKI might be clinically beneficial. Due to the less prominence of Candida albicans in human intestine compared with mouse gut, C. albicans were orally administered in bilateral nephrectomy (BiN) mice. Gut dysbiosis, using microbiome analysis, and gut permeability defect (gut leakage), which was determined by fluorescein isothiocyanate-dextran and intestinal tight-junction immunofluorescent staining, in mice with BiN-Candida was more severe than BiN without Candida. Additionally, profound gut leakage in BiN-Candida also resulted in gut translocation of lipopolysaccharide (LPS) and (1→3)-ß-D-glucan (BG), the organismal components from gut contents, that induced more severe systemic inflammation than BiN without Candida. The co-presentation of LPS and BG in mouse serum enhanced inflammatory responses. As such, LPS with Whole Glucan Particle (WGP, a representative BG) induced more severe macrophage responses than LPS alone as determined by supernatant cytokines and gene expression of downstream signals (NFκB, Malt-1 and Syk). Meanwhile, WGP alone did not induced the responses. In parallel, WGP (with or without LPS), but not LPS alone, accelerated macrophage ATP production (extracellular flux analysis) through the upregulation of genes in mitochondria and glycolysis pathway (using RNA sequencing analysis), without the induction of cell activities. These data indicated a WGP pre-conditioning effect on cell energy augmentation. In conclusion, Candida in BiN mice accelerated gut translocation of BG that augmented cell energy status and enhanced pro-inflammatory macrophage responses. Hence, gut fungi and BG were associated with the enhanced systemic inflammation in acute uremia.


Assuntos
Injúria Renal Aguda/metabolismo , Candida albicans/metabolismo , Inflamação/sangue , Proteoglicanas/sangue , Injúria Renal Aguda/genética , Injúria Renal Aguda/microbiologia , Animais , Candida/metabolismo , Candida albicans/patogenicidade , Disbiose/sangue , Metabolismo Energético , Humanos , Inflamação/microbiologia , Inflamação/patologia , Inflamação/cirurgia , Lipopolissacarídeos/sangue , Macrófagos/metabolismo , Macrófagos/microbiologia , Macrófagos/patologia , Camundongos , Microbiota/genética , Nefrectomia/efeitos adversos
17.
Molecules ; 26(9)2021 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-34066875

RESUMO

The main core of wound treatment is cell growth and anti-infection. To accelerate the proliferation of fibroblasts in the wound and prevent wound infections, various strategies have been tried. It remains a challenge to obtain good cell proliferation and antibacterial effects. Here, human hair kerateine (HHK)/poly(ethylene oxide) (PEO)/poly(vinyl alcohol) (PVA) nanofibers were prepared using cysteine-rich HHK, and then, silver nanoparticles (AgNPs) were in situ anchored in the sulfur-containing amino acid residues of HHK. After the ultrasonic degradation test, HHK/PEO/PVA nanofibrous mats treated with 0.005-M silver nitrate were selected due to their relatively complete structures. It was observed by TEM-EDS that the sulfur-containing amino acids in HHK were the main anchor points of AgNPs. The results of FTIR, XRD and the thermal analysis suggested that the hydrogen bonds between PEO and PVA were broken by HHK and, further, by AgNPs. AgNPs could act as a catalyst to promote the thermal degradation reaction of PVA, PEO and HHK, which was beneficial for silver recycling and medical waste treatment. The antibacterial properties of AgNP-HHK/PEO/PVA nanofibers were examined by the disk diffusion method, and it was observed that they had potential antibacterial capability against Gram-positive bacteria, Gram-negative bacteria and fungi. In addition, HHK in the nanofibrous mats significantly improved the cell proliferation of NIH3T3 cells. These results illustrated that the AgNP-HHK/PEO/PVA nanofibrous mats exhibited excellent antibacterial activity and the ability to promote the proliferation of fibroblasts, reaching our target applications.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Proliferação de Células/efeitos dos fármacos , Queratinas Específicas do Cabelo/química , Nanopartículas Metálicas/química , Nanofibras/química , Polietilenoglicóis/química , Álcool de Polivinil/química , Prata/química , Animais , Candida albicans/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Cabelo/química , Humanos , Ligação de Hidrogênio , Camundongos , Testes de Sensibilidade Microbiana , Células NIH 3T3 , Nitrato de Prata/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Cicatrização/efeitos dos fármacos
18.
Front Cell Infect Microbiol ; 11: 666900, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34178720

RESUMO

The intestinal mucosa is composed of a monolayer of epithelial cells, which is highly polarized and firmly united to each other thanks to the presence of proteins complexes, called Tight junctions (TJs). Alteration of the mucus layer and TJs causes an increase in intestinal permeability, which can lead to a microbial translocation and systemic disorders. Candida albicans, in addition to its role of commensal, is an opportunistic pathogen responsible for disseminated candidiasis, especially in immunocompromised subjects where the dysbiosis leads to damage of the intestinal mucosal barrier . In this work, we used a line of intestinal epithelial cells able to stably express the genes that encodes human beta defensin-2 (HBD-2) and -3 (HBD-3) to monitor the invasion of C. albicans in vitro. Defensins are a group of antimicrobial peptides (AMPs) found in different living organisms, and are involved in the first line of defense in the innate immune response against pathogens. The results obtained show that the presence of antimicrobial peptides improves the expression of TJs and increases the Trans Epithelial Electrical Resistence value. In addition, the invasive ability of C. albicans in transfected cells is significantly reduced, as well as the expression levels of genes involved in the apoptotic pathway. Through the study of interaction between antimicrobial peptides and microbiota we will be able in the future to better understand the mechanisms by which they exert the host defense function against intestinal pathogens.


Assuntos
Candidíase , beta-Defensinas , Candida albicans , Humanos , Mucosa Intestinal , Proteínas Citotóxicas Formadoras de Poros
19.
Front Cell Infect Microbiol ; 11: 680732, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34178723

RESUMO

The yeast Candida albicans exhibits multiple morphologies dependent on environmental cues. Candida albicans biofilms are frequently polymicrobial, enabling interspecies interaction through proximity and contact. The interaction between C. albicans and the bacterium, Pseudomonas aeruginosa, is antagonistic in vitro, with P. aeruginosa repressing the yeast-to-hyphal switch in C. albicans. Previous transcriptional analysis of C. albicans in polymicrobial biofilms with P. aeruginosa revealed upregulation of genes involved in regulation of morphology and biofilm formation, including SET3, a component of the Set3/Hos2 histone deacetylase complex (Set3C). This prompted the question regarding the involvement of SET3 in the interaction between C. albicans and P. aeruginosa, both in vitro and in vivo. We found that SET3 may influence early biofilm formation by C. albicans and the interaction between C. albicans and P. aeruginosa. In addition, although deletion of SET3 did not alter the morphology of C. albicans in the presence of P. aeruginosa, it did cause a reduction in virulence in a Caenorhabditis elegans infection model, even in the presence of P. aeruginosa.


Assuntos
Candida albicans , Pseudomonas aeruginosa , Animais , Biofilmes , Caenorhabditis elegans , Candida albicans/genética , Pseudomonas aeruginosa/genética , Virulência
20.
Int J Mol Sci ; 22(10)2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-34069257

RESUMO

Candida albicans is an opportunistic pathogen that induces vulvovaginal candidiasis (VVC), among other diseases. In the vaginal environment, the source of carbon for C. albicans can be either lactic acid or its dissociated form, lactate. It has been shown that lactate, similar to the popular antifungal drug fluconazole (FLC), reduces the expression of the ERG11 gene and hence the amount of ergosterol in the plasma membrane. The Cdr1 transporter that effluxes xenobiotics from C. albicans cells, including FLC, is delocalized from the plasma membrane to a vacuole under the influence of lactate. Despite the overexpression of the CDR1 gene and the increased activity of Cdr1p, C. albicans is fourfold more sensitive to FLC in the presence of lactate than when glucose is the source of carbon. We propose synergistic effects of lactate and FLC in that they block Cdr1 activity by delocalization due to changes in the ergosterol content of the plasma membrane.


Assuntos
Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Fluconazol/farmacologia , Ácido Láctico/farmacologia , Candida albicans/genética , Candida albicans/metabolismo , Membrana Celular/metabolismo , Farmacorresistência Fúngica/efeitos dos fármacos , Farmacorresistência Fúngica/genética , Sinergismo Farmacológico , Ergosterol/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Glucose/metabolismo , Glucose/farmacologia , Ácido Láctico/metabolismo , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Testes de Sensibilidade Microbiana , Transporte Proteico/efeitos dos fármacos
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