RESUMO
Staphylococcus aureus is a significant Gram-positive bacterium that is associated with a broad spectrum of diseases ranging from minor skin infections to lethal pneumonia, endocarditis, and toxinoses. α-Hemolysin is one of the most important exotoxins that contribute to the pathogenesis of S. aureus infections. Liquiritigenin is one of the most significant active components in licorice. In this study, hemolysis, western blot, and real-time reverse transcription-PCR assays were performed to investigate the impact of liquiritigenin on the production of S. aureus α-hemolysin. The results showed that low concentrations of liquiritigenin remarkably decreased S. aureus α-hemolysin production in a dose-dependent manner. Using live/dead cell staining and lactate dehydrogenase assays, we found that liquiritigenin could protect human lung cells (A549) from α-hemolysin-mediated injury. The data indicated that this compound could potentially be useful in developing drugs aiming at staphylococcal α-hemolysin.
Assuntos
Antibacterianos/farmacologia , Toxinas Bacterianas/antagonistas & inibidores , Flavanonas/farmacologia , Proteínas Hemolisinas/antagonistas & inibidores , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/química , Flavanonas/química , Hemólise/efeitos dos fármacos , Humanos , Lesão Pulmonar , Testes de Sensibilidade Microbiana , Estrutura Molecular , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Staphylococcus aureus/crescimento & desenvolvimentoRESUMO
Staphylococcus aureus causes a broad range of life-threatening diseases in humans. The pathogenicity of this micro-organism is largely dependent upon its virulence factors. One of the most extensively studied virulence factors is the extracellular protein α-toxin. In this study, we show that allicin, an organosulfur compound, was active against S. aureus with MICs ranged from 32 to 64 µg/mL. Haemolysis, Western blot and real-time RT-PCR assays were used to evaluate the effects of allicin on S. aureus α-toxin production and on the levels of gene expression, respectively. The results of our study indicated that sub-inhibitory concentrations of allicin decreased the production of α-toxin in both methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) in a dose-dependent manner. Furthermore, the transcriptional levels of agr (accessory gene regulator) in S. aureus were inhibited by allicin. Therefore, allicin may be useful in the treatment of α-toxin-producing S. aureus infections.
Assuntos
Antibacterianos/farmacologia , Toxinas Bacterianas/metabolismo , Proteínas Hemolisinas/metabolismo , Staphylococcus aureus Resistente à Meticilina/metabolismo , Ácidos Sulfínicos/farmacologia , Animais , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Toxinas Bacterianas/genética , Meios de Cultivo Condicionados , Dissulfetos , Proteínas Hemolisinas/genética , Hemólise , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/crescimento & desenvolvimento , Testes de Sensibilidade Microbiana , Coelhos , Transativadores/genética , Transativadores/metabolismo , Transcrição GênicaRESUMO
Staphylococcal pneumonia provoked by methicillin-resistant Staphylococcus aureus (MRSA) is a life-threatening infection in which α-toxin is an essential virulence factor. In this study, we investigate the influence of naringenin on α-toxin production and further assess its therapeutic performance in the treatment of staphylococcal pneumonia. Remarkably, the expression of α-toxin was significantly inhibited when the organism was treated with 16 µg/ml of naringenin. When studied in a mouse model of S. aureus pneumonia, naringenin could attenuate the symptoms of lung injury and inflammation in infected mice. These results suggest that naringenin is a promising agent for treatment of S. aureus infection.
Assuntos
Toxinas Bacterianas/biossíntese , Flavanonas/uso terapêutico , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Fitoterapia , Extratos Vegetais/uso terapêutico , Pneumonia Estafilocócica/tratamento farmacológico , Fatores de Virulência/biossíntese , Animais , Linhagem Celular , Citrus paradisi/química , Feminino , Flavanonas/farmacologia , Humanos , Inflamação/tratamento farmacológico , Inflamação/microbiologia , Solanum lycopersicum/química , Staphylococcus aureus Resistente à Meticilina/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Extratos Vegetais/farmacologia , Pneumonia Estafilocócica/microbiologiaRESUMO
In the present study, the antimicrobial activity of glycyrrhetinic acid (GA) against Staphylococcus aureus, and its influence on the production of S. aureus alpha-haemolysin (Hla) were investigated, along with the in vivo activity of GA against S. aureus-induced pneumonia. GA could not inhibit the growth of S. aureus, but the secretion of Hla by S. aureus was significantly inhibited by low concentrations of GA in a dose-dependent manner. Furthermore, in vivo data show that GA provides protection against staphylococcal pneumonia in a murine model system.