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1.
Dalton Trans ; 49(18): 6084-6096, 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32319493

RESUMO

Infections of the cow udder leading to mastitis and lower milk quality are one of the biggest problems in the dairy industry worldwide. Unfortunately, therapeutic options for the treatment of cow mastitis are limited as a consequence of the development of pathogens that are resistant to conventionally used antibiotics. In the search for agents that will be active against cow mastitis associated pathogens, in the present study, five new silver(i) complexes with different chelating pyridine-4,5-dicarboxylate types of ligands, [Ag(NO3)(py-2py)]n (1), [Ag(NO3)(py-2metz)]n (2), [Ag(CH3CN)(py-2py)]BF4 (3), [Ag(py-2tz)2]BF4 (4) and [Ag(py-2metz)2]BF4 (5), py-2py is dimethyl 2,2'-bipyridine-4,5-dicarboxylate, py-2metz is dimethyl 2-(4-methylthiazol-2-yl)pyridine-4,5-dicarboxylate and py-2tz is dimethyl 2-(thiazol-2-yl)pyridine-4,5-dicarboxylate, were synthesized, structurally characterized and assessed for in vitro antimicrobial activity using both standard bioassay and clinical isolates from a contaminated milk sample obtained from a cow with mastitis. These complexes showed remarkable activity against the standard panel of microorganisms and a selection of clinical isolates from the milk of the cow diagnosed with mastitis. With the aim of determining the therapeutic potential of silver(i) complexes, their toxicity in vivo against the model organism, Caenorhabditis elegans (C. elegans), was investigated. The complexes that had the best therapeutic profile, 2 and 5, induced bacterial membrane depolarization and the production of reactive oxygen species (ROS) in Candida albicans cells and inhibited the hyphae as well as the biofilm formation. Taken together, the presented data suggest that the silver(i) complexes with pyridine ligands could be considered for the treatment of microbial pathogens, which are causative agents of cow mastitis.


Assuntos
Antifúngicos/farmacologia , Caenorhabditis elegans/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Complexos de Coordenação/farmacologia , Mastite/tratamento farmacológico , Piridinas/química , Prata/farmacologia , Animais , Antifúngicos/síntese química , Antifúngicos/química , Caenorhabditis elegans/patogenicidade , Candida albicans/crescimento & desenvolvimento , Candida albicans/metabolismo , Bovinos , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Cristalografia por Raios X , Feminino , Ligantes , Mastite/microbiologia , Testes de Sensibilidade Microbiana , Modelos Moleculares , Estrutura Molecular , Tamanho da Partícula , Espécies Reativas de Oxigênio/metabolismo , Prata/química , Propriedades de Superfície
2.
Pathog Dis ; 76(4)2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29684116

RESUMO

Pseudomonas aeruginosa has been amongst the top 10 'superbugs' worldwide and is causing infections with poor outcomes in both humans and animals. From 202 P. aeruginosa isolates (n = 121 animal and n = 81 human), 40 were selected on the basis of biofilm-forming ability and were comparatively characterized in terms of virulence determinants to the type strain P. aeruginosa PAO1. Biofilm formation, pyocyanin and hemolysin production, and bacterial motility patterns were compared with the ability to kill human cell line A549 in vitro. On average, there was no significant difference between levels of animal and human cytotoxicity, while human isolates produced higher amounts of pyocyanin, hemolysins and showed increased swimming ability. Non-parametric statistical analysis identified the highest positive correlation between hemolysis and the swarming ability. For the first time an ensemble machine learning approach used on the in vitro virulence data determined the highest relative predictive importance of the submerged biofilm formation for the cytotoxicity, as an indicator of the infection ability. The findings from the in vitro study were validated in vivo using zebrafish (Danio rerio) embryos. This study highlighted no major differences between P. aeruginosa species isolated from animal and human infections and the importance of pyocyanin production in cytotoxicity and infection ability.


Assuntos
Biofilmes/efeitos dos fármacos , Proteínas Hemolisinas/toxicidade , Pseudomonas aeruginosa/patogenicidade , Piocianina/toxicidade , Fatores de Virulência/toxicidade , Células A549 , Animais , Biofilmes/crescimento & desenvolvimento , Sobrevivência Celular/efeitos dos fármacos , Embrião não Mamífero , Expressão Gênica , Proteínas Hemolisinas/biossíntese , Proteínas Hemolisinas/genética , Hemólise/efeitos dos fármacos , Especificidade de Hospedeiro , Humanos , Aprendizado de Máquina , Infecções por Pseudomonas/microbiologia , Infecções por Pseudomonas/patologia , Pseudomonas aeruginosa/crescimento & desenvolvimento , Pseudomonas aeruginosa/metabolismo , Piocianina/biossíntese , Piocianina/genética , Virulência , Fatores de Virulência/biossíntese , Fatores de Virulência/genética , Peixe-Zebra
3.
J Infect Dev Ctries ; 8(7): 914-8, 2014 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-25022304

RESUMO

INTRODUCTION: This study was conducted to evaluate the seroprevalence of West Nile virus (WNV) in the horse population of northern Serbia. Furthermore, it aimed to provide insight and an updated overview on the circulation of this re-emerging pathogen in this part of southeastern Europe. At the time of manuscript preparation, no clinical cases of WNV infection in horses were reported in this area. METHODOLOGY: Between 2007 and 2011, a total of 252 equine serum samples were collected from seven different locations in northern Serbia. The presence of WNV-reactive IgG antibodies was examined by using commercial and in-house ELISAs. Selected ELISA-positive samples were re-tested by a WNV lineage 2 plaque reduction neutralization test 90% (PRNT-90). RESULTS: In 28.6% of the 252 tested equine serum samples antibodies against WNV were detected. The results obtained with the in-house ELISA corresponded to the outcome of the commercial kit in 90% of the samples. All selected WNV antibody ELISA-positive samples were confirmed by PRNT-90 with neutralizing antibody titers of 1:23 to > 1:512. CONCLUSION: This study confirms the circulation of WNV in northern Serbia. No striking regional differences in seroprevalences were identified suggesting WNV circulation also in other parts of Serbia. Distances between wetlands or forests and stud farms do not appear to have an influence on WNV seroprevalence.


Assuntos
Cavalos/virologia , Vírus do Nilo Ocidental/isolamento & purificação , Animais , Anticorpos Antivirais/sangue , Infecções Assintomáticas , Ensaio de Imunoadsorção Enzimática , Doenças dos Cavalos/virologia , Testes de Neutralização , Sérvia , Estudos Soroepidemiológicos , Inquéritos e Questionários , Febre do Nilo Ocidental/veterinária , Febre do Nilo Ocidental/virologia
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