Antibiotic Resistance-modifying Activity Research Articles

Chemical profile of the essential oil of Lippia origanoides Kunth and antibiotic resistance-modifying activity by gaseous contact method

Chemical profile of the essential oil of Lippia origanoides Kunth and antibiotic resistance-modifying activity by gaseous contact method

Hydrocinnamic Acid and Perillyl Alcohol Potentiate the Action of Antibiotics against Escherichia coli.

The treatment of bacterial infections has been troubled by the increased resistance to antibiotics, instigating the search for new antimicrobial therapies. Phytochemicals have demonstrated broad-spectrum and effective antibacterial effects as well as antibiotic resistance-modifying activity. In this study, perillyl alcohol and hydrocinnamic acid were characterized for their antimicrobial action against Escherichia coli. Furthermore, dual and triple combinations of these molecules with the antibiotics chloramphenicol and amoxicillin were investigated for the first time. Perillyl alcohol had a minimum inhibitory concentration (MIC) of 256 µg/mL and a minimum bactericidal concentration (MBC) of 512 µg/mL. Hydrocinnamic acid had a MIC of 2048 µg/mL and an MBC > 2048 µg/mL. Checkerboard and time-kill assays demonstrated synergism or additive effects for the dual combinations chloramphenicol/perillyl alcohol, chloramphenicol/hydrocinnamic acid, and amoxicillin/hydrocinnamic acid at low concentrations of both molecules. Combenefit analysis showed synergism for various concentrations of amoxicillin with each phytochemical. Combinations of chloramphenicol with perillyl alcohol and hydrocinnamic acid revealed synergism mainly at low concentrations of antibiotics (up to 2 μg/mL of chloramphenicol with perillyl alcohol; 0.5 μg/mL of chloramphenicol with hydrocinnamic acid). The results highlight the potential of combinatorial therapies for microbial growth control, where phytochemicals can play an important role as potentiators or resistance-modifying agents.

EVALUATION OF CITRIC ACID AND CLOVE OIL AS SAFE ANTI-VIRULENCE AND RESISTANCE-MODIFYING AGENTS AGAINST PROBLEMATIC KLEBSIELLA CLINICAL ISOLATES IN EGYPT

Klebsiella species are regarded as terrifying pathogens that threaten different healthcare systems. These pathogens possess a variety of virulence factors which markedly account for their pathogenicity. Three virulence factors (capsule formation, hypermucoviscosity and biofilm formation) were screened, phenotypically and genotypically, among selected Egyptian Klebsiella clinical isolates. Two safe edible agents, clove oil and citric acid, were tested for their effect on bacterial capsules using the Anthony capsular staining method and the transmission electron microscopy. The antibiotic-resistance modifying activity of both agents was studied against selected troublesome isolates showing resistance to amikacin, meropenem and cefotaxime. Molecular docking of citric acid and eugenol with NDM-1, as well as the docking of citric acid with AAC(6′)-Ib and CTX-M-15 were carried out to explain the resistance modifying activity of the tested agents. Capsule formation was the most prominent virulence factor that was detected in all isolates. Both citric acid and clove oil could effectively reduce the size of the formed bacterial capsules. Citric acid showed promising synergistic effects when combined with the studied antibiotics against all the tested isolates. However, clove oil showed a synergistic effect only against 50% of the tested isolates when combined with meropenem. Relying on their binding efficiency mode obtained from molecular docking studies, the tested agents were recognized as promising inhibitors of the studied enzymes. In conclusion, both citric acid and clove oil are auspicious anti-virulence and resistance-modifying agents that can be combined with conventional antibiotics to combat virulent and multidrug resistant Klebsiella isolates.

Antibiotic-Potentiating Activity of Phanostenine Isolated from Cissampelos sympodialis Eichler.

Cissampelos sympodialis Eichler is well studied and investigated for its antiasthmatic properties, but there are no data in the literature describing antibacterial properties of alkaloids isolated from this botanical species. This work reports the isolation and characterization of phanostenine obtained from roots of C. sympodialis and describes for the first time its antimicrobial and antibiotic modulatory properties. Phanostenine was first isolated from Cissampelos sympodialis and its antibacterial activities were determined. Chemical structures of the alkaloid isolate were determined using spectroscopic and chemical analyses. Phanostenine was also tested for its antibacterial activity against standard strains and clinical isolates of Escherichia coli and Staphylococcus aureus. Minimal inhibitory concentration (MIC) was determined in a microdilution assay and for the evaluation of antibiotic resistance-modifying activity. MIC of the antibiotics was determined in the presence or absence of phanostenine at sub-inhibitory concentrations. The evaluation of antibacterial activity by microdilution assay showed activity for all strains with better values against S. aureus ATCC 12692 and E. coli 27 (787.69 mm). The evaluation of aminoglycoside antibiotic resistance-modifying activity showed reduction in the MIC of the aminoglycosides (amikacin, gentamicin and neomycin) when associated with phanostenine, MIC reduction of antibiotics ranging from 21 % to 80 %. The data demonstrated that phanostenine possesses a relevant ability to modify the antibiotic activity in vitro. We can suggest that phanostenine presents itself as a promising tool as an adjuvant for novel antibiotics formulations against bacterial resistance.

Phytochemical study of Pilosocereus pachycladus and antibiotic-resistance modifying activity of syringaldehyde

Pilosocereus pachycladus F. Ritter, Cactaceae, popularly known as “facheiro”, is used as food and traditional medicine in Brazilian caatinga ecoregion. The plant is used to treat prostate inflammation and urinary infection. The present work reports the first secondary metabolites isolated from P. pachycladus. Therefore, the isolated compound 4-hydroxy-3,5-dimethoxy benzaldehyde (syringaldehyde) was evaluated as modulator of Staphylococcus aureus pump efflux-mediated antibiotic resistance. The isolation of compounds was performed using chromatographic techniques and the structural elucidation was carried out by spectroscopic methods. In order to evaluate syringaldehyde ability to modulate S. aureus antibiotic resistance, its minimum inhibitory concentrations (μg/ml) was first determinate, then, the tested antibiotics minimum inhibitory concentrations were determined in the presence of the syringaldehyde in a sub-inhibitory concentration. The chromatographic procedures led to isolation of twelve compounds from P. pachycladus including fatty acids, steroids, chlorophyll derivatives, phenolics and a lignan. The syringaldehyde did not show any antibacterial activity at 256μg/ml against S. aureus. On the other hand the compound was able to reduce the antibiotic concentration (tetracycline, norfloxacin, ethidium bromide) required to inhibit the growth of drug-resistant bacteria, showing the ability of syringaldehyde of inhibiting the efflux pump on these bacteria.

Antibacterial and antibiotic-resistance modifying activity of the extracts and compounds from Nauclea pobeguinii against Gram-negative multi-drug resistant phenotypes.

BackgroundMulti-drug resistance of Gram-negative bacteria constitutes a major obstacle in the antibacterial fight worldwide. The discovery of new and effective antimicrobials and/or resistance modulators is necessary to combat the spread of resistance or to reverse the multi-drug resistance. In this study, we investigated the antibacterial and antibiotic-resistance modifying activities against 29 Gram-negative bacteria including multi-drug resistant (MDR) phenotypes of the methanol extracts from Nauclea pobeguiinii leaves (NPL), Nauclea pobeguiinii bark (NPB) and six compounds from the bark extract, identified as 3-acetoxy-11-oxo-urs-12-ene (1), p-coumaric acid (2), citric acid trimethyl ester (3), resveratrol (4), resveratrol β-D-glucopyranoside (5) and strictosamide (6).MethodsThe broth microdilution method was used to determine the minimal inhibitory concentrations (MIC) and minimal bactericidal concentrations (MBC) of crude extracts and compounds as well as the antibiotic-resistance modifying effects of MPB and 4.ResultsMIC determinations indicate values ranging from 32-1024 μg/mL for NPB and NPL on 89.7 % and 69.0 % of the tested bacterial strains respectively. MIC values below 100 μg/mL were obtained with NPB against Escherichia coli ATCC10536, AG100 and Enterobacter aerogenes CM64 strains. The lowest MIC value for crude extracts of 32 μg/mL was obtained with NPB against E. coli ATCC10536. Compound 4 was active all tested bacteria, whilst 1, 3 and 6 displayed weak and selective inhibitory effects. The corresponding MIC value (16 μg/mL) was obtained with 4 against Klebsiella pneumoniae KP55 strain. Synergistic effects of the combination of NPB with chloramphenicol (CHL), kanamycin (KAN) as well as that of compound 4 with streptomycin (STR) and ciprofloxacin (CIP) were observed.ConclusionThe present study provides information on the possible use of Nauclea pobeguinii and compound 4 in the control of Gram-negative bacterial infections including MDR phenotypes. It also indicates that NPB and 4 can be used as naturally occurring antibiotic-resistance modulators to tackle MDR bacteria.Electronic supplementary materialThe online version of this article (doi:10.1186/s12906-016-1173-2) contains supplementary material, which is available to authorized users.

Chemical composition and possible use as adjuvant of the antibiotic therapy of the essential oil of Rosmarinus officinalis L.

Rosmarinus officinalis L. (rosemary) essential oil (REO) was tested for its antimicrobial activity alone and in combination with conventional antibiotics used against Staphylococcus aureus, Escherichia coli, and Candida strains. The essential oil was chemically described using GC–MS analysis and its antibiotic-resistance modifying activity was assayed using microdilution method. A significant modulatory effect on the drug resistance was verified when the REO was used in association with aminoglycoside antibiotics against E. coli and S. aureus multidrug resistant strains. With respect to the antifungal tested, there was a decrease on amphotericin B activity when this antibiotic was tested in association with the REO against Candida krusei. On the other hand, the combined use of the REO with benzoilmetronidazole was more effective than the antibiotic alone when tested against C. krusei. Rosemary essential oil could become a promising source of metabolites with antibiotic-resistance modifying activity for use against multi-drug-resistant microorganisms.

In VitroAntibacterial and Antibiotic Resistance Modifying Effect of Bioactive Plant Extracts on Methicillin-ResistantStaphylococcus epidermidis

The crude extracts of plants from Asteraceae and Lamiaceae family and essential oils from Salvia officinalis and Salvia sclarea were studied for their antibacterial as well as antibiotic resistance modifying activity. Using disc diffusion and broth microdilution assays we determined higher antibacterial effect of three Salvia spp. and by evaluating the leakage of 260 nm absorbing material we detected effect of extracts and, namely, of essential oils on the disruption of cytoplasmic membrane. The evaluation of in vitro interactions between plant extracts and oxacillin described in terms of fractional inhibitory concentration (FIC) indices revealed synergistic or additive effects of plant extracts and clearly synergistic effects of essential oil from Salvia officinalis with oxacillin in methicillin-resistant Staphylococcus epidermidis.

Chemical composition and synergistic interaction between aminoglycosides antibiotics and essential oil of Lantana montevidensis Briq.

The chemical composition of the essential oil from Lantana montevidensis Briq. and its antibiotic resistance modifying activity were investigated by gas chromatography/mass spectrometry (GC/MS) and microdilution assay, respectively. β-Caryophyllene (31.50%), germacrene D (27.50%) and bicyclogermacrene (13.93%) were the main constituents. The essential oil was examined for antibiotic activity alone in association with aminoglycosides against Escherichia coli Ec27 and Staphylococcus aureus Sa358. The results showed antibacterial activities of the oil and synergistic effects combined with aminoglycosides. The most expressive effect was the potentiating of amikacin on E. coli with minimal inhibitory concentration decrease (512–5 µg mL−1). The data obtained are indicative of the antibacterial activity of the essential oil of L. montevidensis and its potential in modifying the resistance of aminoglycosides analysed.

Fruits to potentiate the antibiotic activity: The effect ofEugenia unifloraandEugenia jambolanumL. against MRSA

Some Staphylococcus species are frequently recognized as etiological agents of many animal and human opportunistic infections. This is the first report testing the antibiotic resistance-modifying activity of Eugenia jambolanum and Eugenia uniflora against methicillin-resistant Staphylococcus aureus — MRSA strain. In this study, the ethanol extracts of Eugenia jambolanum L., Eugenia uniflora L. and chlorpromazine were tested for their antimicrobial activity alone or in combination with aminoglycosides against an MRSA strain using microdilution method. Synergism between both extracts and all aminoglycosides assayed was demonstrated, except E. jambolanum and tobramycin. In the same form, synergism was observed between chlorpromazine and kanamicin, neomycin and tobramicin, 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 to modif...

Effect of ethnomedicinal plants used in folklore medicine in Jordan as antibiotic resistant inhibitors on Escherichia coli

BackgroundEscherichia coli occurs naturally in the human gut; however, certain strains that can cause infections, are becoming resistant to antibiotics. Multidrug-resistant E. coli that produce extended-spectrum β lactamases (ESBLs), such as the CTX-M enzymes, have emerged within the community setting as an important cause of urinary tract infections (UTIs) and bloodstream infections may be associated with these community-onsets. This is the first report testing the antibiotic resistance-modifying activity of nineteen Jordanian plants against multidrug-resistant E. coli.MethodsThe susceptibility of bacterial isolates to antibiotics was tested by determining their minimum inhibitory concentrations (MICs) using a broth microdilution method. Nineteen Jordanian plant extracts (Capparis spinosa L., Artemisia herba-alba Asso, Echinops polyceras Boiss., Gundelia tournefortii L, Varthemia iphionoides Boiss. & Blanche, Eruca sativa Mill., Euphorbia macroclada L., Hypericum trequetrifolium Turra, Achillea santolina L., Mentha longifolia Host, Origanum syriacum L., Phlomis brachydo(Boiss.) Zohary, Teucrium polium L., Anagyris foetida L., Trigonella foenum-graecum L., Thea sinensis L., Hibiscus sabdariffa L., Lepidium sativum L., Pimpinella anisum L.) were combined with antibiotics, from different classes, and the inhibitory effect of the combinations was estimated.ResultsMethanolic extracts of the plant materials enhanced the inhibitory effects of chloramphenicol, neomycin, doxycycline, cephalexin and nalidixic acid against both the standard strain and to a lesser extent the resistant strain of E. coli. Two edible plant extracts (Gundelia tournefortii L. and Pimpinella anisum L.) generally enhanced activity against resistant strain. Some of the plant extracts like Origanum syriacum L.(Labiateae), Trigonella foenum- graecum L.(Leguminosae), Euphorbia macroclada (Euphorbiaceae) and Hibiscus sabdariffa (Malvaceae) did not enhance the activity of amoxicillin against both standard and resistant E. coli. On the other hand combinations of amoxicillin with other plant extracts used showed variable effect between standard and resistant strains. Plant extracts like Anagyris foetida (Leguminosae) and Lepidium sativum (Umbelliferae) reduced the activity of amoxicillin against the standard strain but enhanced the activity against resistant strains. Three edible plants; Gundelia tournefortii L. (Compositae) Eruca sativa Mill. (Cruciferae), and Origanum syriacum L. (Labiateae), enhanced activity of clarithromycin against the resistant E. coli strain.ConclusionThis study probably suggests possibility of concurrent use of these antibiotics and plant extracts in treating infections caused by E. coli or at least the concomitant administration may not impair the antimicrobial activity of these antibiotics.

Herbal therapy associated with antibiotic therapy: potentiation of the antibiotic activity against methicillin – resistant Staphylococcus aureus by Turnera ulmifolia L

BackgroundStaphylococcus genus is widely spread in nature being part of the indigenous microbiota of skin and mucosa of animal and birds. Some Staphylococcus species are frequently recognized as etiological agents of many animal and human opportunistic infections This is the first report testing the antibiotic resistance-modifying activity of Turnera ulmifolia against methicillin-resistant Staphylococcus aureus – MRSA strain.MethodsIn this study an ethanol extract of Turnera ulmifolia L. and chlorpromazine were tested for their antimicrobial activity alone or in combination with aminoglycosides against an MRSA strain.ResultsThe synergism of the ethanol extract and aminoglycosides were verified using microdillution method. A synergistic effect of this extract on gentamicin and kanamycin was demonstrated. Similarly, a potentiating effect of chlorpromazine on kanamycin, gentamicin and neomycin, indicating the involvement of an efflux system in the resistance to these aminoglycosides.ConclusionIt is therefore suggested that extracts from Turnera ulmifolia could be used as a source of plant-derived natural products with resistance-modifying activity, constituting a new weapon against the problem of bacterial resistance to antibiotics demonstrated in MRSA strains.

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.