RESUMEN
OBJECTIVES: The aims of this study were to identify the active ingredients from Portulaca oleraceaâ L. (PO) that could provide synergism with antibiotics against methicillin-resistant Staphylococcus aureus (MRSA) and their possible mechanisms of resistance inhibition. METHODS: High-speed counter-current chromatography (HSCCC) coupled with gas chromatography-mass spectrometry and a panel of laboratory MRSA strains were used for checkerboard and efflux inhibitory assays. KEY FINDINGS: Linoleic and oleic acids were identified from HSCCC fraction 18 of PO with synergistic antibacterial activity when combined with erythromycin against RN4220/pUL5054. Ethidium bromide efflux inhibitory studies revealed that linoleic and oleic acids may interfere the activity of MsrA pump. By comparing among a panel of linoleic and oleic acids analogues, unsaturated fatty acids in salt form with cis configuration and an increase in number of double bonds were found to further increase the antibacterial activity when used alone or in combination with antibiotics. CONCLUSION: This study reported for the first time that two active ingredients, namely linoleic and oleic acids, were identified from PO with synergistic antibacterial activity when combined with erythromycin against MRSA RN4220/pUL5054 and possibly act by inhibiting the efflux pumps of the bacteria cells.
Asunto(s)
Antibacterianos/farmacología , Eritromicina/farmacología , Ácido Linoleico/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Ácido Oléico/farmacología , Portulaca , Ciprofloxacina/farmacología , Sinergismo Farmacológico , Quimioterapia Combinada , Cromatografía de Gases y Espectrometría de Masas , Ácido Linoleico/química , Pruebas de Sensibilidad Microbiana , Ácido Oléico/química , Extractos Vegetales/químicaRESUMEN
Bacterial resistance to antibiotics has become a serious problem of public health that concerns almost all currently used antibacterial agents and that manifests in all fields of their application. To find more antibacterial agents from natural resources is all the time considered as an important strategy. Sophora flavescens is a popularly used antibacterial herb in Chinese Medicine, from which prenylated flavones were reported as the antibacterial ingredients but with a major concern of toxicity. In our screening on the antibacterial activities of various chemicals of this herb, 18 fractions were obtained from 8 g of 50% ethanol extract on a preparative high-speed counter-current chromatography (HSCCC, 1000 ml). The system of n-hexane/ethyl acetate/methanol/water (1:1:1:1) was used as the two-phase separation solvent. A chalcone named kuraridin was isolated from the best anti-MRSA fraction, together with sophoraflavanone G, a known active ingredient of S. flavescens. Their structures were elucidated by analysis of the NMR spectra. Both compounds exhibited significant anti-MRSA effects, compared to baicalein that is a well known anti-MRSA natural product. More important, kuraridin showed no toxicity on human peripheral blood mononuclear cells (PBMC) at the concentration up to 64 µg/ml while sophoraflavanone G inhibited over 50% of cellular activity at 4 µg/ml or higher concentration. These data suggested that opening of ring A of the prenylated flavones might decrease the toxicity and remain the anti-MRSA effect, from a viewpoint of structure-activity relationship.
Asunto(s)
Antibacterianos/aislamiento & purificación , Chalconas/aislamiento & purificación , Distribución en Contracorriente/métodos , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Monoterpenos/aislamiento & purificación , Sophora/química , Antibacterianos/química , Antibacterianos/farmacología , Supervivencia Celular/efectos de los fármacos , Chalconas/química , Chalconas/farmacología , Cromatografía Líquida de Alta Presión , Flavanonas/química , Flavanonas/aislamiento & purificación , Flavanonas/farmacología , Humanos , Leucocitos Mononucleares , Pruebas de Sensibilidad Microbiana , Monoterpenos/química , Monoterpenos/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacología , Raíces de Plantas/químicaAsunto(s)
Antibacterianos/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Pruebas de Sensibilidad Microbiana/normas , Vancomicina/farmacología , Hong Kong , Humanos , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiologíaRESUMEN
A range of silver-coated or -impregnated dressings are now commercially available for use but comparative data on their antimicrobial efficacies are limited. The antibacterial activities of five commercially available silver-coated/impregnated dressings were compared against nine common burn-wound pathogens, namely methicillin-sensitive and -resistant Staphylococcus aureus (MRSA), Enterococcus faecalis, Pseudomonas aeruginosa, Escherichia coli, Enterobacter cloacae, Proteus vulgaris, Acinetobacter baumannii and a multi-drug-efflux-positive Acinetobacter baumannii (BM4454), using a broth culture method. The rapidity and extent of killing of these pathogens under in vitro conditions were evaluated. All five silver-impregnated dressings investigated exerted bactericidal activity, particularly against Gram-negative bacteria, including Enterobacter species, Proteus species and E. coli. The spectrum and rapidity of action, however, ranged widely for different dressings. Acticoat and Contreet had a broad spectrum of bactericidal activities against both Gram-positive and -negative bacteria. Contreet was characterized by a very rapid bactericidal action and achieved a reduction of > or =10,000 c.f.u. ml(-1) in the first 30 min for Enterobacter cloacae, Proteus vulgaris, Pseudomonas aeruginosa and Acinetobacter baumanii. Other dressings demonstrated a narrower range of bactericidal activities. Understanding the characteristics of these dressings may enable them to be targeted more appropriately according to the specific requirements for use of a particular dressing, as in for prophylaxis in skin grafting or for an infected wound with MRSA.