RESUMEN
This study aimed to evaluate the antimicrobial activity of the dichloromethane fraction (DCMF) from the stem bark of Mimosa caesalpiniifolia and its effect on the activity of conventional antibiotics against Staphylococcus aureus strains overexpressing specific efflux pump genes. DCMF showed activity against S. aureus, Staphylococcus epidermidis and Candida albicans. Addition of DCMF at subinhibitory concentrations to the growth media enhanced the activity of norfloxacin, ciprofloxacin and ethidium bromide against S. aureus strains overexpressing norA suggesting the presence of efflux pump inhibitors in its composition. Similar results were verified for tetracycline against S. aureus overexpressing tetK, as well as, for ethidium bromide against S. aureus overexpressing qacC. These results indicate that M. caesalpiniifolia is a source of molecules able to modulate the fluoroquinolone- and tetracycline-resistance in S. aureus probably by inhibition of NorA, TetK and QacC respectively. SIGNIFICANCE AND IMPACT OF THE STUDY: Drug resistance is a common problem in patients with infectious diseases. Dichloromethane fraction from the stem bark of Mimosa caesalpiniifolia showed antimicrobial activity against Gram-positive bacterium Staphylococcus aureus and against Candida albicans, but did not show activity against Gram-negative specie Escherichia coli. Moreover, this fraction was able to potentiate the action of norfloxacin, ciprofloxacin and tetracycline against S. aureus strains overexpressing different efflux pump genes. Thus, Mimosa caesalpiniifolia is a source of efflux pump inhibitors which could be used in combination with fluoroquinolones or tetracycline in the treatment of infectious diseases caused by S. aureus strains overexpressing efflux pump genes.
Asunto(s)
Antibacterianos/farmacología , Candida albicans/efectos de los fármacos , Mimosa/química , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus aureus/efectos de los fármacos , Staphylococcus epidermidis/efectos de los fármacos , Antiportadores/genética , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Ciprofloxacina/farmacología , Resistencia a Múltiples Medicamentos/genética , Etidio/farmacología , Fluoroquinolonas/farmacología , Humanos , Cloruro de Metileno/química , Pruebas de Sensibilidad Microbiana , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , Norfloxacino/farmacología , Corteza de la Planta/química , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/genética , Tetraciclina/farmacología , Resistencia a la Tetraciclina/genéticaRESUMEN
AIM: The goal of this study was to increase knowledge about the antimicrobial activity of some synthetic Riparin-derived compounds, alone or in combination with fluoroquinolone antibiotics, against a strain of Staphylococcus aureus resistant to fluoroquinolone by way of overexpression of the NorA efflux pump. METHODS AND RESULTS: Microdilution tests showed that Riparins A and B did not show any significant antibacterial activity against Staph. aureus strains. On the other hand, the intrinsic antibacterial activity increased with increasing lipophilicity of the compounds, in the following order: Riparin-D (MIC 256 µg ml-1 ; Log P 2·95) < Riparin-C (MIC 102 µg ml-1 ; Log P 3·22) < Riparin-E (MIC 16 µg ml-1 ; Log P 3·57). The addition of all riparins to growth media at subinhibitory concentrations caused an increase in the antibacterial activity of antibiotics against the NorA-overexpressing test strain. Riparin-B, which has two methoxyl groups at the phenethyl moiety, showed the best modulatory effect. CONCLUSIONS: Riparin-E is a good anti-staphylococci agent, while Riparin-B functions as a NorA efflux pump inhibitor. SIGNIFICANCE AND IMPACT OF THE STUDY: Our data suggest the possibility of using Riparin-B in combination with norfloxacin or ciprofloxacin for therapy of infections caused by multi-drug resistant Staph. aureus.
Asunto(s)
Antibacterianos/farmacología , Proteínas Bacterianas/antagonistas & inhibidores , Benzamidas/farmacología , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/antagonistas & inhibidores , Staphylococcus aureus/efectos de los fármacos , Antibacterianos/química , Benzamidas/química , Farmacorresistencia Bacteriana , Fluoroquinolonas/farmacologíaRESUMEN
Among 46 isolates of Staphylococcus aureus obtained from cattle in the State of Paraíba, Brazil, four were shown to produce antimicrobial substances (AMS). The two best AMS producers carried single plasmids of about 8.0 kbp and 50 kbp, respectively, which were designated pRJ34 and pRJ35. Curing experiments and molecular analysis associated the AMS production with the presence of these plasmids in the cells. The biochemical properties exhibited by the AMS suggested that they might be bacteriocins (Bac). The bacteriocin encoded by pRJ34 showed properties identical to those of the bacteriocins encoded by other small staphylococcal Bac plasmids. However, the bacteriocin encoded by the large plasmid pRJ35 has shown some properties which distinguish it from the other bacteriocins of Staph. aureus described so far, suggesting it may be a new member of the staphylococcal bacteriocin family.