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1.
Int J Med Microbiol ; 310(3): 151410, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32057619

RESUMO

The study aims to explore the combinatorial effect of naringin with antibiotics, ciprofloxacin and tetracycline on Pseudomonas aeruginosa biofilms. The antibiofilm efficacy of selected treatment regimes against P. aeruginosa biofilm were quantified by crystal violet assay, MTT assay, Congo red binding assay, and were visualized by confocal laser scanning microscopy and scanning electron microscopy. All the assays reflected antibiofilm activities, however, combinatorial performances of naringin with antibiotics were found to be more significant. A significant reduction in swimming and swarming motilities along with pellicle formation and altered colony morphology were observed as a result of combinatorial effect. The cytotoxicity of naringin and its antibiotic combinations was assayed on murine macrophage cell line. The applicability of such combinations was tested for their relative eradication against pre-formed biofilm on urinary catheter surface. This finding indicated that naringin potentiates the efficacy of both ciprofloxacin and tetracycline on P. aeruginosa biofilm in comparison to their solo treatment. The finding would help to open hitherto unexplored possibilities of establishing naringin as a potential antibiofilm agent and suggest on the possibility of its use in drug-herb combinations for managing biofilm-associated bacterial infections.


Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Ciprofloxacina/farmacologia , Flavanonas/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Tetraciclina/farmacologia , Animais , Linhagem Celular , Macrófagos/efeitos dos fármacos , Camundongos , Testes de Sensibilidade Microbiana , Infecções por Pseudomonas/microbiologia
2.
Curr Drug Discov Technol ; 17(4): 542-552, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31250760

RESUMO

BACKGROUND: It was apparent by the end of 1980s that the success against the threats of bacterial pathogens on public health was an illusion, with the rapid development of resistant strains more than the discovery of new drugs. As a consequence, the remedial services were in the backfoot position of being on the losing side of this never-ending evolutionary war. The quest for new antibiotics to overcome resistance problems has long been a top research priority for the researchers and the pharmaceutical industry. However, the resistance problems remain unresolved due to the abrupt misuse of antibiotics by common people, which has immensely worsened the scenario by disseminating antibiotic-resistant bacterial strains around the world. OBJECTIVE: Thus, immediate action is needed to measure emerging and re-emerging microbial diseases having new resistance mechanisms and to manage their rapid spread among the common public by means of novel alternative metabolites. CONCLUSION: Antimicrobial Peptides (AMPs) are short, cationic peptides evolved in a wide range of living organisms and serve as the essential part of the host innate immunity. For humans, these effector molecules either can directly kill the foreign microbes or modulate the host immune systems so that the human body could develop some resistance against the microbial infections. In this review, we discuss their history, structural classifications, modes of action, and explain their biological roles as anti-infective agents. We also scrutinize their clinical potentiality, current limitations in various developmental stages and strategies to overcome for their successful clinical applications.


Assuntos
Anti-Infecciosos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Desenvolvimento de Medicamentos/tendências , Infecções/tratamento farmacológico , Animais , Anti-Infecciosos/uso terapêutico , Peptídeos Catiônicos Antimicrobianos/uso terapêutico , Bactérias/efeitos dos fármacos , Bactérias/patogenicidade , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Resistência Microbiana a Medicamentos/imunologia , Fungos/efeitos dos fármacos , Fungos/patogenicidade , Humanos , Imunidade Inata/efeitos dos fármacos , Infecções/microbiologia , Infecções/parasitologia , Parasitos/efeitos dos fármacos , Parasitos/patogenicidade , Vírus/efeitos dos fármacos , Vírus/patogenicidade
3.
Microb Pathog ; 138: 103790, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31605761

RESUMO

This study investigated the effects of reserpine, the main bioactive compound of Rauwolfia serpentina, on biofilm formation and biofilm-associated virulence factors production in a Gram-positive pathogen, Staphylococcus aureus. Crystal violet assay, MTT assay, Congo red binding, CLSM studies were performed to assess the antibiofilm activity. Molecular docking was performed to explain the possible mode of action, catheter model was used to evaluate its application potential and the combinatorial study was performed in search of an improved therapeutic formulation. Reserpine affected biofilm formation, EPS production, biofilm cell viability and virulence factor production. It could eradicate 72.7% biofilm at ½â€¯× MIC dose and could also stop the metabolic activity of 50.6% bacterial cells in a biofilm. Staphylococcus aureus biofilm- and virulence-regulatory proteins like AgrA, AtlE, Bap, IcaA, SarA and SasG were found to interact with reserpine which might lead to the attenuation of its pathogenicity. Reserpine along with other commercial antibiotics could generate a hightened antibiofilm response, and also eradicated a good percentage of bacterial biofilm from a urinary catheter model. These findings suggested reserpine as a good alternative entity to generate new improved therapeutic formulations.


Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Reserpina/farmacologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/fisiologia , Virulência/efeitos dos fármacos , Antibacterianos/química , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Fenômenos Químicos , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Hemólise , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Modelos Moleculares , Ligação Proteica , Reserpina/química , Infecções Estafilocócicas/tratamento farmacológico , Relação Estrutura-Atividade
4.
Biofouling ; 34(3): 320-334, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29482361

RESUMO

This study aimed to evaluate the effect of reserpine, a plant-derived indole-alkaloid, against Pseudomonas aeruginosa PAO1 biofilms. The anti-biofilm activity of reserpine was evaluated by crystal violet staining, MTT assay, confocal laser scanning microscopy and scanning electron microscopy. Reserpine effects were also assessed by qRT-PCR of quorum sensing (QS)-regulated genes and biochemical quantification of the QS-mediated virulence factors pyocyanin, rhamnolipids, proteases and elastases. Reserpine reduced biofilm formation, cell motility, virulence factor production, and QS-controlled gene expression. Additionally, molecular docking analysis for AHL synthase LasI and QS transcriptional regulators LasR/MvfR revealed a plausible molecular mechanisms of reserpine QS inhibition. These findings provide insights into the underlying mode of action of reserpine, which may be useful in the development of new drugs against biofilm-related infections.


Assuntos
Proteínas de Bactérias/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Percepção de Quorum/efeitos dos fármacos , Reserpina/farmacologia , Antibacterianos/farmacologia , Biofilmes/crescimento & desenvolvimento , Glicolipídeos , Ligases/efeitos dos fármacos , Simulação de Acoplamento Molecular , Pseudomonas aeruginosa/metabolismo , Pseudomonas aeruginosa/fisiologia , Fatores de Virulência
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