José P. Siqueira-Júnior

Enhancement of the Antibiotic Activity against a Multiresistant Escherichia coli by Mentha arvensis L. and Chlorpromazine

Background: This is the first report testing the antibiotic resistance-modifying activity of Mentha arvensis. Methods: In this study an ethanol extract of M. arvensis L. and chlorpromazine were tested for their antimicrobial activity alone or in combination with conventional antibiotics against strains of Escherichia coli. Results: The growth of two E. coli strains tested was not inhibited by the extract. The minimum inhibitory concentration and minimal bactericide concentration values were ≧1 mg/ml for both strains of E. coli used. A potentiating effect of this extract on gentamicin was demonstrated. Similarly, there was a potentiating effect of chlorpromazine on kanamycin, amikacin and tobramycin, indicating the involvement of an efflux system in the resistance to these aminoglycosides. Conclusions: It is therefore suggested that extracts from M. arvensis could be used as a source of plant-derived natural products with resistance-modifying activity, such as in the case of gentamicin, constituting a new weapon against bacterial resistance to antibiotics, as with chlorpromazine.

In vitro anti-staphylococcal activity of Hyptis martiusii Benth against methicillin-resistant Staphylococcus aureus: MRSA strains

This is the first report about the antibacterial activity of Hyptis martiusii Benth. In this study the ethanol extract of H. martiusii was tested for its antimicrobial activity against strains of Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. The growth of all bacterial strains tested was inhibited by the extract. The diameter of inhibition zones varied from 13 to 20 mm for the extract. The MIC and MBC values ranged from 128 to > 1024mg/mL and 256 to > 1024 mg/mL, respectively. It is therefore suggested that extracts from H. martiusii could be used as an anti-Staphylococcus agent. Compared with methicillin and gentamicin, the extract was more effective, being a promising antibacterial agent.

Modulation of drug resistance in Staphylococcus aureus by a kaempferol glycoside from Herissantia tiubae (Malvaceae).

In an ongoing project to evaluate natural compounds isolated from plants from the Brazilian biodiversity as modulators of antibiotic resistance, kaempferol‐3‐O‐β‐d‐(6″‐E‐p‐coumaroyl) glucopyranoside (tiliroside), isolated from Herissantia tiubae (Malvaceae) was investigated using the strain SA‐1199B of Staphylococcus aureus, which overexpresses the norA gene encoding the NorA efflux protein which extrudes hydrophilic fluorquinolones and some biocides, such as benzalkonium chloride, cetrimide, acriflavine and ethidium bromide. The minimum inhibitory concentrations (MICs) of the antibiotics and biocides were determined by the microdilution assay in the absence and in the presence of sub‐inhibitory concentration of tiliroside. Although tiliroside did not display relevant antibacterial activity (MIC = 256 µg/mL), it modulated the activity of antibiotics, i.e. in combination with antibiotics a reduction in the MIC was observed for norfloxacin (16‐fold), ciprofloxacin (16‐fold), lomefloxacin (four‐fold) and ofloxacin (two‐fold), and an impressive reduction in the MICs for the biocides (up to 128‐fold). The results presented here represent the first report of a kaempferol glycoside as a putative efflux pump inhibitor in bacteria. The present finding indicates that H. tiubae (and broadly Malvaceae) could serve as a source of plant‐derived natural products that modulate bacterial resistance, i.e. a source of potential adjuvants of antibiotics. Copyright

Effect of Momordica charantia L. in the resistance to aminoglycosides in methicilin-resistant Staphylococcus aureus

In this study the ethanol extract (EEMC) of Momordica charantia L. (Cucurbitaceae) was tested for its modifying antibiotic activity against a MRSA strain. The growth of an MRSA (SA358) in the absence and presence of aminoglycosides was evaluated. A potentiating effect between this extract and all aminoglycosides was demonstrated. Similarly, the same effect was shown by chlorpromazine on kanamycin, gentamicin and neomycin, indicating the involvement of an efflux system in the resistance to these aminoglycosides. Extracts from M. charantia could be used as a source of plant-derived natural products with resistance-modifying activity. This is the first report about the modifying antibiotic activity of M. charantia, constituting a new weapon against multi-resistant bacteria such as MRSA.

Flavonoids from Praxelis clematidea R.M. King and Robinson modulate bacterial drug resistance.

Chemical studies of Praxelis clematidea R.M. King & Robinson resulted in the isolation of six flavones: Apigenine, genkwanine, 7,4’-dimethylapigenin, trimethylapigenin, cirsimaritin and tetramethylscutellarein, which were tested for their toxicity against Staphylococcus aureus SA-1199B, a strain possessing the NorA efflux pump. Efflux pumps are integral proteins of the bacterial membrane and are recognized as one of the main causes of bacterial drug resistance, since they expel antibiotics from the cell. The inhibition of this transporter is one form of modulating bacterial resistance to antimicrobial drugs. The flavones tested did not show any significant antibacterial activity against the Staphylococcus aureus strain used, but were able to modulate bacterial drug resistance. This property might be related to the degree of lipophilicity of the flavones conferred by the methoxyl groups, since 4’,5,6,7 tetramethoxyflavone the most methoxylated compound, reduced the minimal inhibitory concentration of the drug 16-fold.

Antibiotic activity of the extract of Punica granatum Linn. over bovine strains of Staphylococcus aureus

A medicina humana e veterinaria tem falhado no tratamento de infeccoes em longo prazo causadas por Staphylococcus aureus associadas ao desenvolvimento de resistencia a agentes antimicrobianos. A atividade antimicrobiana do extrato da casca do fruto de Punica granatum Linn. foi avaliada sobre 38 linhagens de S. aureus de origem bovina para a determinacao da concentracao inibitoria minima (CIM). Das 38 linhagens ensaiadas, 22 sao resistentes a penicilina.(PRSA). O extrato de P. granatum apresentou potencial acao antimicrobiana sobre todas as linhagens ensaiadas formando halos de inibicao variando de 10 a 36 mm de diâmetro. Os resultados deste estudo confirmam a eficacia do extrato de P. granatum como potencial agente antibacteriano sobre S. aureus e demonstram a importância de se avaliar novas substâncias com potencial antimicrobiano, o que pode contribuir para a terapeutica alternativa em Medicina Veterinaria.

Potentiation of Antibiotic Activity by Eugenia uniflora and Eugenia jambolanum

This is the first report about the modifying antibiotic activity of Eugenia uniflora L. and Eugenia jambolanum L. In this study the ethanol extract of E. uniflora and E. jambolanum was tested for their antimicrobial activity against strains of Escherichia coli. The growth of the two strains of E. coli bacteria tested was not inhibited in a clinically relevant form by the extract. The minimal inhibitory concentration was >or=1,024 microg/mL for both strains of E. coli assayed. Synergism between this extract and gentamicin was demonstrated. In the same extract synergism was observed between chlorpromazine and kanamycin and between amikacin and tobramycin, indicating the involvement of an efflux system in the resistance to these aminoglycosides. It is therefore suggested that extracts from E. uniflora L. and E. jambolanum L. could be used as a source of plant-derived natural products with modifying antibiotic activity to gentamicin.

Enhancement of the Norfloxacin Antibiotic Activity by Gaseous Contact with the Essential Oil of Croton zehntneri

This is the first on the modulation of norfloxacin antibiotic activity by the volatile compounds of an essential oil. We report the chemical composition and antibiotic modifying activity of the essential oil extracted from the leaves of Croton zehntneri Pax et Hoffm (variety estragole), using the minimal inhibitory dose method and gaseous contact. The leaves of Croton zehntneri Pax et Hoffm (Euphorbiaceae) were subjected to hydrodistillation, and the essential oil extracted was examined with respect to the chemical composition, by gas chromatography-mass spectrometry (GC/MS), and to inhibitory activity of efflux pump by gaseous contact. The main component of the essential oil of C. zehntneri was estragole (76,8%). The gaseous components of the oil enhanced the inhibition zone of norfloxacin in 39,5%. This result shows that this oil influences the antibiotic activity of norfloxacin, possibly affecting the bacterial NorA efflux system, and may be used as an adjuvant in the antibiotic therapy of multidrug resistant pathogens.

Composição química e modulação da resistência bacteriana a drogas do óleo essencial das folhas de Rollinia leptopetala R. E. Fries

The essential oil from the leaves of Rollinia leptopetala was obtained by hydrodistillation in Clevengers apparatus and its chemical composition was analyzed by GC-MS. With this technique could be identified 22 constituents in a complex mixture of monoterpenes (54.5%) and sesquiterpenes (45.5%). The main component found in the leaves was the bicyclogermacrene (22.47%). The essential oil was assayed against a strain of Staphylococcus aureus possessing efflux mechanism of resistance to norfloxacin. Although the essential oil did not display relevant antibacterial activity in vitro, it modulated the activity of the norfloxacin, i.e. in combination with the antibiotic it was observed a fourfold reduction in the minimum inhibitory concentration for norfloxacin, indicating inhibition of efflux pump.

Phenolic compounds from Sidastrum micranthum (A. St.-Hil.) fryxell and evaluation of acacetin and 7,4'-Di-O-methylisoscutellarein as motulator of bacterial drug resistence

From the aerial parts of Sidastrum micranthum (A. St.-Hil.) Fryxell (Malvaceae) were isolated m-methoxy-p-hydroxy-benzaldehyde, o-hydroxy-benzoic acid, acacetin, quercetin, 7,4′-Di-O-methylisoscutellarein, genkwanin and tiliroside. These compounds were identified by data analyses of spectroscopic methods. Although acacetin and 7,4′-Di-O-methylisoscutellarein did not display relevant antibacterial activity (MIC = 256 µg/mL), they modulated the activity of antibiotics, i.e. in combination with antibiotics at 64 µg/mL (¼ MIC), a two-fold reduction in the MIC was observed for norfloxacin and ethidium bromide; regarding tetracycline and erythromycin a two-fold reduction in the MIC was observed only with 7,4′-Di-O-methylisoscutellarein.