RESUMEN
Compounds capable of inhibiting the efflux pump mechanism are a promising alternative against bacterial resistance because, when combined with antibiotics, they can increase the effectiveness of these drugs by inhibiting active efflux. Elaiophylin, derived from Streptomyces hygroscopicus, is a natural antibiotic that exhibits a variety of biological activities, including antibacterial activity. However, its potential as an inhibitor of the bacterial efflux mechanism has not been investigated. This study evaluated the ability of Elaiophylin to inhibit the NorA efflux pump in Staphylococcus aureus strains. Therefore, tests were performed to obtain the Minimum Inhibitory Concentration (MIC) and to verify the ability of Elaiophylin to potentiate the MIC of the antibiotic Norfloxacin and Ethidium Bromide (EtBr), known substrates of NorA efflux. Real-time PCR and molecular docking assays were also performed to assess the potential of Elaiophylin against NorA. The strains SA-1199 (wild type) and SA-1199B (NorA over-expressed) of S. aureus were used for this study. The results showed that Elaiophylin significantly decreased the MIC of Norfloxacin and EtBr, increasing the activity of these substrates against S. aureus, which carries the efflux protein NorA. However, Elaiophylin provided a non-significant reduction in norA gene expression, however, molecular docking demonstrated a high binding affinity between Elaiophylin and NorA efflux protein, indicating that Elaiophylin can act as a potential NorA in S. aureus.
Asunto(s)
Proteínas Bacterianas/metabolismo , Macrólidos/farmacología , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , Streptomyces/química , Antibacterianos/farmacología , Proteínas Bacterianas/genética , Sitios de Unión , Farmacorresistencia Bacteriana Múltiple , Regulación Bacteriana de la Expresión Génica/efectos de los fármacos , Macrólidos/química , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Conformación Proteica , Relación Estructura-ActividadRESUMEN
Staphylococcus aureus produces a large variety of exotoxins: staphylococcal enterotoxins (SEs) which cause staphylococcal food poisoning, resulting from the consumption of food containing preformed SEs, Exfoliative Toxin (ET) responsible for the staphylococcal scalded-skin syndrome, mainly in children, and the Toxic Shock Syndrome Toxin 1 (TSST-1) characterized by high fever, hypotension, multiorgan involvement and desquamation of the skin. Due to the importance of this microorganism for the public health, the aim of this study was to review the mainly aspects about staphylococcal exotoxins, including biochemical, genetics and diagnosis characterization.
Staphylococcus aureus produz uma grande variedade de exotoxinas: as Enterototoxinas Estafilocócicas (SEs) que causam intoxicação alimentar estafilocócica, resultante do consumo de alimentos contendo SEs pré-formadas, Toxina Esfoliativa (ET) causadora da síndrome da pele escaldada, principalmente em crianças, e a Toxina-1 da Síndrome do Choque Tóxico (TSST-1), caracterizada por febre, hipotensão, envolvimento multiorgânico e descamação da pele. Devido á importância desta bactéria para a saúde pública objetivou-se com este trabalho revisar os principais aspectos das exotoxinas estafilocócicas, dando ênfase á caracterização bioquímica, genética e aos métodos de detecção destas toxinas.
RESUMEN
Staphylococcus aureus produces a large variety of exotoxins: staphylococcal enterotoxins (SEs) which cause staphylococcal food poisoning, resulting from the consumption of food containing preformed SEs, Exfoliative Toxin (ET) responsible for the staphylococcal scalded-skin syndrome, mainly in children, and the Toxic Shock Syndrome Toxin 1 (TSST-1) characterized by high fever, hypotension, multiorgan involvement and desquamation of the skin. Due to the importance of this microorganism for the public health, the aim of this study was to review the mainly aspects about staphylococcal exotoxins, including biochemical, genetics and diagnosis characterization.
Staphylococcus aureus produz uma grande variedade de exotoxinas: as Enterototoxinas Estafilocócicas (SEs) que causam intoxicação alimentar estafilocócica, resultante do consumo de alimentos contendo SEs pré-formadas, Toxina Esfoliativa (ET) causadora da síndrome da pele escaldada, principalmente em crianças, e a Toxina-1 da Síndrome do Choque Tóxico (TSST-1), caracterizada por febre, hipotensão, envolvimento multiorgânico e descamação da pele. Devido á importância desta bactéria para a saúde pública objetivou-se com este trabalho revisar os principais aspectos das exotoxinas estafilocócicas, dando ênfase á caracterização bioquímica, genética e aos métodos de detecção destas toxinas.