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1.
Sci Rep ; 13(1): 22548, 2023 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-38110428

RESUMO

Overexpression of NorA efflux pumps plays a pivotal role in the multidrug-resistance mechanism in S. aureus. Here, we investigated the activities of prenylated isoflavonoids, present in the legume plant family (Fabaceae), as natural efflux pump inhibitors (EPIs) in fluoroquinolone-resistant S. aureus. We found that four prenylated isoflavonoids, namely neobavaisoflavone, glabrene, glyceollin I, and glyceollin III, showed efflux pump inhibition in the norA overexpressing S. aureus. At sub-inhibitory concentrations, neobavaisoflavone (6.25 µg/mL, 19 µM) and glabrene (12.5 µg/mL, 39 µM), showed up to 6 times more Eth accumulation in norA overexpressing S. aureus than in the control. In addition, these two compounds boosted the MIC of fluoroquinolones up to eightfold. No fluoroquinolone potentiation was observed with these isoflavonoids in the norA knockout strain, indicating NorA as the main target of these potential EPIs. In comparison to the reported NorA EPI reserpine, neobavaisoflavone showed similar potentiation of fluoroquinolone activity at 10 µM, higher Eth accumulation, and less cytotoxicity. Neobavaisoflavone and glabrene did not exhibit membrane permeabilization effects or cytotoxicity on Caco-2 cells. In conclusion, our findings suggest that the prenylated isoflavonoids neobavaisoflavone and glabrene are promising phytochemicals that could be developed as antimicrobials and resistance-modifying agents to treat fluoroquinolone-resistant S. aureus strains.


Assuntos
Fabaceae , Flavonas , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Staphylococcus aureus , Antibacterianos/farmacologia , Antibacterianos/química , Ciprofloxacina/farmacologia , Staphylococcus aureus Resistente à Meticilina/metabolismo , Fabaceae/metabolismo , Células CACO-2 , Proteínas Associadas à Resistência a Múltiplos Medicamentos , Fluoroquinolonas/farmacologia , Flavonas/farmacologia , Proteínas de Bactérias/metabolismo , Testes de Sensibilidade Microbiana
2.
Front Nutr ; 7: 612397, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33521038

RESUMO

Allergen recognition and processing by antigen presenting cells is essential for the sensitization step of food allergy. Macrophages and dendritic cells are both phagocytic antigen presenting cells and play important roles in innate immune responses and signaling between the innate and adaptive immune system. To obtain a model system with a homogeneous genetic background, we derived macrophages and dendritic cells from THP-1 monocytes. The difference between macrophages and dendritic cells was clearly shown by differences in their transcription response (microarray) and protein expression levels. Their resemblance to primary cells was analyzed by comparison to properties as described in literature. The uptake of ß-lactoglobulin after wet-heating (60°C in solution) by THP-1 derived macrophages was earlier reported to be significantly increased. To analyse the subsequent immune response, we incubated THP-1 derived macrophages and dendritic cells with native and differently processed ß-lactoglobulin and determined the transcription and cytokine expression levels of the cells. A stronger transcriptional response was found in macrophages than in dendritic cells, while severely structurally modified ß-lactoglobulin induced a more limited transcriptional response, especially when compared to native and limitedly modified ß-lactoglobulin. These results show that processing is relevant for the transcriptional response toward ß-lactoglobulin of innate immune cells.

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