RESUMEN
Bacterial RecA plays an important role in the evaluation of antibiotic resistance via stress-induced DNA repair mechanism; SOS response. Accordingly, RecA became an important therapeutic target against antimicrobial resistance. Small molecule inhibitors of RecA may prevent adaptation of antibiotic resistance mutations and the emergence of antimicrobial resistance. In our study, we observed that phenolic compound p-Coumaric acid as potent RecA inhibitor. It inhibited RecA driven biochemical activities in vitro such as ssDNA binding, strand exchange, ATP hydrolysis and RecA coprotease activity of E. coli and L. monocytogenes RecA proteins. The mechanism underlying such inhibitory action of p-Coumaric acid involves its ability to interfere with the DNA binding domain of RecA protein. p-Coumaric acid also potentiates the activity of ciprofloxacin by inhibiting drastic cell survival of L. monocytogenes as well as filamentation process; the bacteria defensive mechanism in response to DNA damage. Additionally, it also blocked the ciprofloxacin induced RecA expression leading to suppression of SOS response in L. monocytogenes. These findings revealed that p-Coumaric acid is a potent RecA inhibitor, and can be used as an adjuvant to the existing antibiotics which not only enhance the shelf-life but also slow down the emergence of antibiotic resistance in bacteria.
Asunto(s)
Antibacterianos/farmacología , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Listeria monocytogenes/efectos de los fármacos , Propionatos/farmacología , Rec A Recombinasas/antagonistas & inhibidores , Respuesta SOS en Genética/efectos de los fármacos , Adenosina Trifosfato/metabolismo , Ciprofloxacina/farmacología , Ácidos Cumáricos , Reparación del ADN/efectos de los fármacos , ADN Bacteriano/antagonistas & inhibidores , ADN Bacteriano/genética , ADN Bacteriano/metabolismo , Farmacorresistencia Bacteriana Múltiple/genética , Sinergismo Farmacológico , Escherichia coli/efectos de los fármacos , Escherichia coli/genética , Escherichia coli/crecimiento & desarrollo , Escherichia coli/metabolismo , Expresión Génica , Hidrólisis/efectos de los fármacos , Listeria monocytogenes/genética , Listeria monocytogenes/crecimiento & desarrollo , Listeria monocytogenes/metabolismo , Pruebas de Sensibilidad Microbiana , Rec A Recombinasas/genética , Rec A Recombinasas/metabolismo , Recombinación Genética/efectos de los fármacosRESUMEN
The antibacterial activities of vulgarone B, a component of Artemisia iwayomogi essential oil, were evaluated against some antibiotic-susceptible and -resistant human pathogens. Moreover, the effects of combining antibiotics, such as oxacillin, with vulgarone B were determined in this study. Significant inhibitory activities of Artemisia oils against antibiotic-susceptible and -resistant bacteria were confirmed by broth microdilution methods. The effects of vulgarone B on bacterial morphology and DNA were observed by scanning electron microscope and electrophoresis, respectively. In checkerboard microtiter tests, vulgarone B and A. iwayomogi oil combined with oxacillin resulted in synergism, or additive effects. Moreover, the safety of Artemisia oil and vulgarone B were confirmed in vivo. Both vulgarone B and the essential oil fraction of A. iwayomogi showed significant inhibitory activities against strains of antibioticsusceptible and -resistant bacteria. The oils showed synergism or additive effects when combined with oxacillin against two strains of Staphylococcus aureus. The antibiotic mechanism involved might be related to DNA cleavage. Thus, vulgarone B and the essential oil fraction of A. iwayomogi may be promising candidates for a safe, effective, natural agent active against antibiotic-resistant S. aureus, especially when combined with oxacillin.