Indifferent Effect Research Articles

Antifungal activity of plant-derived compounds and their synergism against major postharvest pathogens of longan fruit in vitro

The aim of this study was to find alternatives to conventional synthetic fungicides to control postharvest decay of longan fruit. The antifungal potential of thymol, carvacrol and trans-cinnamaldehyde was evaluated against four major longan pathogens, Lasiodiplodia spp., Phomopsis spp., Pestalotiopsis spp. and Geotrichum candidum, using vapor phase and direct contact methods. The vapor phase of all active compounds was more effective on fungal growth than direct contact. A volatile vapor of thymol and carvacrol had strong antifungal activity against the tested fungi, exhibiting minimum inhibitory concentration (MIC) in the range of 40 to 80 mg/L air; trans-cinnamaldehyde showed the least efficiency, with MIC ranging from 80 to 160 mg/L air for G. candidum and Phomopsis spp., while it could not inhibit Lasiodiplodia spp. and Pestalotiopsis spp. at 160 mg/L air. The minimum fungicidal concentration (MFC) of thymol and carvacrol varied from 40 to 80 mg/L air, while trans-cinnamaldehyde completely inhibited the mycelial growth of the tested fungi at higher concentrations. Mycelial growth of all tested fungi decreased with increasing active compound concentration, except for trans-cinnamaldehyde. Thymol proved to be the most effective compound against the four tested fungi, with effective concentration 50 (EC50) of 5.68 ± 0.59, 6.86 ± 0.52, 8.27 ± 0.22 and 9.99 ± 1.28 mg/L air for Lasiodiplodia spp., Phomopsis spp., Pestalotiopsis spp. and G. candidum, respectively. Fungal growth curves were adequately fitted (0.958 < R2 < 0.996) by a modified Gompertz model. For all tested fungi, the lag phase (λ) of fungal mycelia exposed to thymol and carvacrol increased, while the maximum colony diameter (A) and maximum growth rate (vm) decreased. A combination of thymol and carvacrol exhibited an antagonistic effect against G. candidum but an indifferent effect against Lasiodiplodia spp., Phomopsis spp. and Pestalotiopsis spp.

Efektivitas Kombinasi Vankomisin dan Vitamin C terhadap Pertumbuhan MRSA (Methicillin Resistant Staphylococcus aureus) (Effectiveness of Vancomycin and Vitamin C Combination on MRSA (Methicillin Resistant Staphylococcus aureus) Growth)

&#x0D; Nephrotoxicity due to prolonged use of vancomycin becomes a big issue in patients with MRSA infections and the use of vitamin C has been proved to decrease this side effect. Vitamin C with its combination with antibiotic will halt MRSA growth by forming Reactive Oxygen Species (ROS). This study aimed to determine the effect of vancomycin and vitamin C combination in order to halt the MRSA growth and the minimum concentration of vitamin C which can decrease the Minimum Inhibitory Concentration (MIC) of vancomycin. This study used a quasi experimental design with 7 groups, 1 as negative control which only given vancomycin and 6 other groups which given vancomycin and vitamin C with following concentration 0,4; 0,8; 1,6; 3,2; 6,4; and 12,8 mg/mL. We used microdilution method with 4 repetitions to measure the MIC value. This study revealed that there were no difference between control and other groups, the MIC of vancomycin is 1 µg/mL. Combination effect was measured by Fractional Inhibitory Concentration Index (FICI) calculation which showed indifferent effect to all groups. This study concluded that combination of vancomycin and vitamin C effect has no difference with control group and by adding vitamin C until 12,8 mg/mL did not decrease MRSA growth. &#x0D; &#x0D; Keywords: MRSA, vancomycin, vitamin C, Minimum Inhibitory Concentration (MIC) &#x0D;

Modulation of plant extracts on the resistance of staphylococcus aureus strains to antibiotics

Introduction:The increase in bacterial resistance has generated the need to increase research for the discovery of new drugs, and medicinal plants are a proven source of bioactive products with great therapeutic potential. Objectives: To analyze the modulating activity of the ethanolic extracts of cumaru, angico, artemisia, terramicina and espinheira in front of strains of Staphylococcus aureus. Methods: Modulating activity was determined by the disc diffusion method, analyzing three strains of multiresistant Staphylococcus aureus with the antibiotics erythromycin, vancomycin, clindamycin, oxacillin, gentamicin, chloramphenicol, cipropofloxacin and cefoxitin. Each antibiotic disk was soaked with 20μL of the extract. The disks were placed on the surface of the culture medium already seeded with the microorganisms and incubated at 35 ° C for 24 hours. The diameters of inhibition halos (HI) were measured in mm and compared to those determined by HI of the antibiotics alone. The increase in HI diameter ≥ 2 mm, synergistic effect; antagonistic effect when the HI diameter was smaller than that of the isolated antibiotic; and, indifferent effect, when the increase in HI diameter <2 mm in relation to the antibiotic alone. Results and Discussion: The crude extracts evaluated were able to modulate the activity of different antibiotics of clinical use by means of synergistic, indifferent or antagonistic actions. For the UFPEDA 707 strain of Staphylococcus aureus, were observed 45% of synergism, 35% of indifference and 20% of antagonism. Analyzing the responses with Staphylococcus aureus UFPEDA 728, 25% of synergistic effects, 30% of indifferent effect and 45% of antagonistic effect. In contrast to Staphylococcus aureus UFPEDA 732, synergism occurred in 35%, indifference in 50% and antagonism in 15%. Conclusions: The extract that was able to modulate the activity of the antibiotics with the synergic effect for the three isolates tested was the ethanolic extract of angico.

Antimicrobial Susceptibility among Colistin, Sulbactam, and Fosfomycin and a Synergism Study of Colistin in Combination with Sulbactam or Fosfomycin against Clinical Isolates of Carbapenem-Resistant Acinetobacter baumannii.

This in vitro study aimed to determine the activity of colistin plus sulbactam and colistin plus fosfomycin against carbapenem-resistant A. baumannii (CRAB). Fifteen clinical isolates were obtained from patients admitted to Phyathai II International Hospital, Bangkok, Thailand, from August 2014 to April 2015. The antimicrobial susceptibilities of colistin, sulbactam, and fosfomycin were evaluated using the E-test or broth microdilution and the synergistic activity of the antibacterial combinations (colistin plus sulbactam or fosfomycin) was determined using the chequerboard method. Clonal relationships were explored using repetitive element palindromic- (REP-) PCR. The CRAB isolates were categorized by REP-PCR in 8 groups [A-H]. All CRAB isolates were universally susceptible to colistin but only 20.0% were susceptible to sulbactam. The MIC ranges for colistin, sulbactam, and fosfomycin were 0.75–2 mg/L, 2–96 mg/L, and 64–256 mg/L, respectively. A chequerboard assay revealed that the rates of synergistic and additive effect rates of colistin plus sulbactam and colistin plus fosfomycin were 53.3% and 73.3% of isolates, respectively. No antagonistic effect in any colistin-based combination was observed. However, almost CRAB strains in clone A showed the synergy or additive effects of colistin-sulbactam combination, whereas the other clone (B-H) mostly showed indifferent effects. In conclusion, colistin plus sulbactam and colistin plus fosfomycin against CRAB seem to be interesting option but the efficacy in clinical use has to be evaluated.

ANTIBACTERIAL AND ANTI-INFLAMMATORY ACTIVITIES OF CRUDE EXTRACTS OF THREE TOGOLESE MEDICINAL PLANTS AGAINST ESBL KLEBSIELLA PNEUMONIAE STRAINS

Background: Pithecellobium dulce (Roxb.) Benth., Securidaca longepedunculata Fresn and Cryptolepis sanguinolenta (Lindl.) Schlt are three plants widely used in the Togolese traditional medicine to treat microbial infections. Some studies reported their antibacterial activity alone but until know there no data concerning their possible interaction with conventional antibiotics. The main objective of this study was to investigate the antibacterial activity of the association of the crude extracts of the three plants with some conventional antibiotics. We further evaluate the antioxidant and the anti-inflammatory activities of the extracts on rat’s model.&#x0D; Materials and methods:The antimicrobial activity was evaluated by the broth microdilution assay and the Fractional inhibitory concentrations (FIC) determined by the checkerboard method. The anti-inflammatory activity was evaluated using the Carrageenan- induced rat paw edema model. The antioxidant activities and the phenol contents were determined by spectrophotometry.&#x0D; Results: The MICs of hydroethanolic extract of plants ranged from 3.125 to 100 mg/mL on Klebsiella pneumoniae strains. Synergistic action was observed only with the combination of Imipenem/P. dulce, imipenem/C. sanguinolenta, amikacin/P. dulce and amikacin/C. sanguinolenta against the ESBL negative Klebsiella pneumoniae strain. Of the 21 associations, 15 were antagonistic on the ESBL-producing strains. The indifference effect was observed with the combination of the extract of Securidaca longepedunculata and the following antibiotics imipenem, amikacin, tetracyclin, ciprofloxacin, Cefotaxim; and Sulfametoxazol+Trimethoprim. The in vitro anti-inflammatory with Lipoxygenase inhibition activity was best with C. sanguinolenta extract while the in vivo paw edema model revealed that S. longepedunculata was the highest reducer of paw edema. In addition white blood cells count and biochemical parameters such as total proteins and immunoglobulins were significantly affected by the administration of plant extracts.&#x0D; Conclusion: This study revealed that the three plants although they may inhibit the bacterial growth by themselves, but there is also a possible synergistic action with the commercial antibiotics. Further investigations are needed to identify the active compounds and their mechanism of action.

In vitro activity of some essential oils alone and in combination against the fish pathogen Nocardia seriolae.

Microplate resazurin assay was applied to investigate the in vitro activity of four essential oils (EOs); cinnamon (Cinnamomum zeylanicum), thyme (Thymus vulgaris), lemongrass (Cymbopogon flexuosus) and tea tree (Melaleuca alternifolia) oils against 80 clinical isolates of the fish pathogen Nocardia seriolae. The checkerboard test was then used to determine the possible synergistic effect of EOs combination against reference type strains of fish nocardiosis. All tested EOs had antibacterial activity against N. seriolae isolates. Among the tested EOs, cinnamon and thyme oils both exhibited the lowest minimum inhibitory concentrations (MICs) with 5-160 and 10-160 μg/ml, respectively. The activities of lemongrass and tea tree EOs were noted to be less effective with MICs of 20-640 and 160->5120 μg/ml, respectively. The checkerboard panel of cinnamon-thyme EOs combination against N. seriolae ATCC43993 demonstrated a synergistic effect with a fractional inhibitory concentration (FIC) index of 0.75. For N. salmonicida ATCC27463, the combination panel showed an additive effect with an FIC index of 1.0. For N. asteroides ATCC19247, the combination panel demonstrated an indifference effect with an FIC index of 1.125. These results indicate that thyme and cinnamon oils alone or the combination of them at a given ratio has a promising potent clinical significance in the treatment of fish nocardiosis. Despite the promising results given by our in vitro studies, the clinical benefits of these EOs combinations can only be determined through carefully designed in vivo experimental studies.

Synergistic Effect of Pleuromutilins with Other Antimicrobial Agents against Staphylococcus aureus In Vitro and in an Experimental Galleria mellonella Model.

Invasive infections due to Staphylococcus aureus, including methicillin-resistant S. aureus are prevalent and life-threatening. Combinations of antibiotic therapy have been employed in many clinical settings for improving therapeutic efficacy, reducing side effects of drugs, and development of antibiotic resistance. Pleuromutilins have a potential to be developed as a new class of antibiotics for systemic use in humans. In the current study, we investigated the relationship between pleuromutilins, including valnemulin, tiamulin, and retapamulin, and 13 other antibiotics representing different mechanisms of action, against methicillin-susceptible and -resistant S. aureus both in vitro and in an experimental Galleria mellonella model. In vitro synergistic effects were observed in combination of all three study pleuromutilins with tetracycline (TET) by standard checkerboard and/or time-kill assays. In addition, the combination of pleuromutilins with ciprofloxacin or enrofloxacin showed antagonistic effects, while the rest combinations presented indifferent effects. Importantly, all study pleuromutilins in combination with TET significantly enhanced survival rates as compared to the single drug treatment in the G. mellonella model caused by S. aureus strains. Taken together, these results demonstrated synergy effects between pleuromutilins and TET against S. aureus both in vitro and in vivo.

Design and pharmacodynamics of recombinant NZ2114 histidine mutants with improved activity against methicillin-resistant Staphylococcus aureus

NZ2114 is a promising candidate for therapeutic application owing to its potent activity to Staphylococcus aureus. Our objective was to identify NZ2114 derivatives with improved activity through substitution of His16 and His18 with residues Arginine and Lysine. Eight mutants were designed and expressed in Pichia pastoris X-33 via pPICZαA. Five of them exhibited strong antimicrobial activity against S. aureus at low minimal inhibitory concentrations (MICs) of 0.057–0.454 μM. Among them, H1, H2, and H3 showed ideal pharmacodynamic effects on methicillin-resistant S. aureus ATCC43300. The total protein level of H1, H2, and H3 reached 1.70, 1.77 and 1.54 g/l at 120 h of induction in the 5-l fermenter, respectively. They killed over 99.9% of pathogens within 1.5 h at 2× and 4× MIC. The post antibiotic effect of H1, H2 and H3 to S. aureus ATCC43300 was 2.94, 1.75 and 1.55 h at 2× MIC, which was similar with their original peptide NZ2114 (1.43 h) and vancomycin (1.72 h). The fractional inhibitory concentration index (FICI) indicated indifferent effects between H1, H2, H3 and vancomycin, ampicillin, rifampicin. Additionally, they had low hemolysis and high stability in different environments (temperature, pH, proteases, and saline ions). All results indicate that H1, H2, and H3 can be produced in large-scale and have potential as therapeutic drugs against MRSA.

Penentuan Nilai FICI Kombinasi Ekstrak Etanol Kulit Daun Lidah Buaya (Aloe vera (L) Burm.f) dan Gentamisin Sulfat Terhadap Bakteri Escherichia coli

The combined use of natural materials and antibiotic compound is one of treatment that can be done against infections caused by bacteria. This combination is expected to inhibit the bacteria is more potent and low side effects. FICI ( Fractional Inhibitory Concentration Index ) is an index that can indicate the activity of a combination of natural ingredients and antibiotic compounds. FICI would indicate that the combination has a synergistic effect, additive, indifferent or antagonistic. This study aims to determine the FICI to the combination of Aloe vera leaves skin ( Aloe vera (L.) Burm.f.) ethanol extract and gentamicin sulphate to the Escherichia coli . Determination of FICI performed with disc diffusion method. The concentration combination of Aloe vera leaves skin ( Aloe vera (L.) Burm.f.) ethanol extract and gen tamicin sulphate used is 1.25 mg / mL + 2 , 5 µg/ mL did not form a zone of inhibition; and 2.5 mg / ml + 5 µg/ mL forming inhibitory zone of 6.95 mm; 6.75 mm; and 6.65 mm. These results suggest that the combination of Aloe vera leaves skin ( Aloe vera (L.) Burm.f.) ethanol extract and gentamicin sulphate against the Escherichia coli has the indifference effect on Escherichia coli , and FICI to this combination is 2.

In vitro synergistic activities of cefazolin and nisin A against mastitis pathogens.

First-generation cephalosporins such as cefazolin (CEZ) have been widely used for mastitis treatment in dairy cattle. However, the use of antibiotics results in the presence of antibiotic residues in milk, which is used for human consumption. Nisin A, a bacteriocin produced by Lactococcus lactis, has been used as a broad-spectrum food preservative for over 50 years. Therefore, a combination of CEZ and nisin A might provide an extended activity spectrum against mastitis pathogens and reduce the antibiotic dose for mastitis treatment. This study aimed to evaluate the combined effect of CEZ and nisin A against mastitis pathogens using the checkerboard and time-kill assays. In the checkerboard assay, the CEZ-nisin A combination exhibited a synergistic effect against Staphylococcus aureus (n=20/20) and Enterococcus faecalis (n=13/18), and meanwhile exhibited a mostly additive effect against Staphylococcus intermedius (n=12/20), Streptococcus agalactiae (n=10/10), Streptococcus dysgalactiae (n=18/18), and Escherichia coli (n=14/18). There were no indifferent or antagonistic effects between CEZ and nisin A. In the time-kill assay, the CEZ-nisin A combination at 0.5 × or 1 × minimum inhibitory concentration exhibited synergistic reduction of bacterial growth by over 3 log10 colony forming units per ml relative to that observed with either antimicrobial substance alone. These results suggest that the CEZ-nisin A combination can be used for developing an intramammary infusion for mastitis treatment, with lower antibiotic concentrations than normal.

Temporal variability of the quality of Taraxacum officinale seed progeny from the East-Ural radioactive trace: is there an interaction between low level radiation and weather conditions?

Hypothesis: The multiple stressors, in different combinations, may impact differently upon seed quality, and low-level doses of radiation may enhance synergistic or antagonistic effects.Results: During 1991–2014 we investigated the quality of the dandelion (Taraxacum officinale s.l.) seed progeny growing under low-level radiation exposure at the East-Ural Radioactive Trace (EURT) area (result of the Kyshtym accident, Russia), and in plants from areas exposed to background radiation. The viability of the dandelion seed progeny was assessed according to chronic radiation exposure, accounting for the variability of weather conditions among years. Environmental factors (temperature, precipitation, and their ratio in different months) can modify the radiobiological effects. We found a wide range of possible responses to multiple stressors: inhibition, stimulation, and indifferent effects in different seasons.Conclusion: The intraspecific variability of the quality of dandelion seed progeny was greatly increased under conditions of low doses of chronic irradiation. Temperature was the most significant factor for seed progeny formation in the EURT zone, whereas the sums of precipitation and ratios of precipitation to temperature dominantly affected organisms from the background population.

A novel interpretation of the Fractional Inhibitory Concentration Index: The case Origanum vulgare L. and Leptospermum scoparium J. R. et G. Forst essential oils against Staphylococcus aureus strains

Origanum vulgare (oregano) and Leptospermum scoparium (manuka) were traditionally employed as natural remedies for infected wounds and skin injuries where Staphylococcus aureus is mainly involved.The first aim of this study was to investigate oregano and manuka essential oils (EOs) chemical compositions and evaluate their antibacterial activity (MIC, Minimum Inhibitory Concentration) against fourteen S. aureus wild strains. The second aim was to evaluate the antibacterial activities of oregano and manuka EOs mixed in different combination (FIC, Fractional Inhibitory Concentration) with an improved chequerboard technique. This allowed to avoid the usual uncertainty in the determination of MIC and FIC values and to obtain a more precise interpretation of FIC indexes (FICIs). Moreover, FICIs were discussed on the basis of a novel interpretation method to evaluate the synergistic/antagonistic effect of EOs mixtures.The most representative compounds in oregano EO were Carvacrol (65.93%), p-Cymene (9.33%) and γ-Terpinene (5.25%), while in manuka EO were Leptospermone (31.65%), cis-Calamenene (15.93%) and Flavesone (6.92%). EOs presented MIC values ranging from 1:2048 to 1:4096 v/v and FIC values ranging from 0.125 to 1.According to our interpretation, a synergistic effect (34.68%), a commutative effect (15.32%) and an indifferent effect (50.00%) and no antagonistic effect were observed. Conversely, according to two previously proposed FICI interpretation models, 1.80% synergistic effect could be observed and, respectively, 98.20% indifferent effect or 48.20% additive effect and 50.00% indifferent effect.As practical results, oregano and manuka EOs may be an effective alternative to chemotherapic drugs in staphylococcal infections and useful tools to enhance food security.

ANTIBACTERIAL ACTIVITY OF AQUEOUS GARLIC EXTRACT ON BETA-LACTAMASE PRODUCING ACINETOBACTER ISOLATES FROM SKIN AND SOFT TISSUE INFECTIONS

Objective: The present study evaluates the antibacterial effect of aqueous garlic extract (AGE) on beta-lactamase producing Acinetobacter strains isolated from skin and soft tissue infections (SSTIs).Methods: A total of 41 non-duplicate strains of Acinetobacter isolated from SSTIs specimens were tested for their antibiotic susceptibility pattern by Kirby-Bauer disk diffusion method. Ceftazidime-resistant Acinetobacter strains were screened for beta-lactamase production by Phenotypic confirmatory disc diffusion test (PCDDT) and E-test. Antibacterial activity of AGE was examined by the disc diffusion method and the minimum inhibitory concentration (MIC) of AGE and Cefotaxime was determined by the agar dilution technique. The combined activity of AGE and Cefotaxime was evaluated by calculating the fractional inhibitory concentration (FIC) index by the checkerboard method.Results: 21 Acinetobacter strains were confirmed to be beta-lactamase producers, out of which 6 were Metallo-beta-lactamase (MBL) producers, 3 were Ambler Class C (AmpC) and 12 were multiple beta-lactamase producers. AGE exhibited significant antibacterial activity as the observed zones of inhibition ranged from 18 - 31 mm against the test strains. The MIC of AGE was in the range of 0.5% - 2% (2.5 mg/ml – 10 mg/ml) with a mean of 0.86% (4.28 mg/ml). 11 test strains showed synergism, 5 strains exhibited additive and indifferent effect, each. By HPLC analysis the concentration of allicin was found to be 0.20, expressed as percentage w/w.Conclusion: It can be stated that aqueous garlic extract might have therapeutic value against beta-lactamase producing Acinetobacter isolates from SSTIs.

Phenolic profiles and antimicrobial activity of various plant resins as potential botanical sources of Serbian propolis

Extensive employment of plant resins and propolis, as an antiseptic agents dating from ancient times in numerous cultures indicating that it may have antimicrobial and other biological properties. Resins from deciduous trees from the Populus and Salix genera, several fruit trees from the genus Prunus and a few other species were analyzed for their phenolic composition and antibacterial activity. Phenolic profiling of the plant resins was performed by high-performance thin-layer chromatography (HPTLC) and ultra-high-performance liquid chromatography (UHPLC) coupled with hybrid mass spectrometry. Antimicrobial activity against seven bacterial species was determined by minimum inhibitory concentration (MIC) assays and bioautography. The synergism, additivism, and antagonism of phenolic compounds were used to define the nature and type of interactions. Populus spp. showed higher amounts of p-hydroxybenzoic acid, p-coumaric acid, caffeic acid, chrysin, apigenin, quercetin, pinocembrin, pinobanksin and galangin, which confirmed the botanical origin of the orange and blue types of propolis. In addition, Gram-positive bacteria exhibited high susceptibility to poplar samples while being resistant to samples from other origins. Cherry bud samples had high amounts of naringenin and showed strong activity against Bacillus subtilis and Listeria monocytogenes. The combinations of tested phenolics showed mainly additive or indifferent effects.

Bacterial Cell Growth Inhibitors Targeting Undecaprenyl Diphosphate Synthase and Undecaprenyl Diphosphate Phosphatase.

We synthesized a series of benzoic acids and phenylphosphonic acids and investigated their effects on the growth of Staphylococcus aureus and Bacillus subtilis. One of the most active compounds, 5-fluoro-2-(3-(octyloxy)benzamido)benzoic acid (7, ED50 ∼0.15 μg mL-1 ) acted synergistically with seven antibiotics known to target bacterial cell-wall biosynthesis (a fractional inhibitory concentration index (FICI) of ∼0.35, on average) but had indifferent effects in combinations with six non-cell-wall biosynthesis inhibitors (average FICI∼1.45). The most active compounds were found to inhibit two enzymes involved in isoprenoid/bacterial cell-wall biosynthesis: undecaprenyl diphosphate synthase (UPPS) and undecaprenyl diphosphate phosphatase (UPPP), but not farnesyl diphosphate synthase, and there were good correlations between bacterial cell growth inhibition, UPPS inhibition, and UPPP inhibition.

Isoprenoid Biosynthesis Inhibitors Targeting Bacterial Cell Growth.

We synthesized potential inhibitors of farnesyl diphosphate synthase (FPPS), undecaprenyl diphosphate synthase (UPPS), or undecaprenyl diphosphate phosphatase (UPPP), and tested them in bacterial cell growth and enzyme inhibition assays. The most active compounds were found to be bisphosphonates with electron-withdrawing aryl-alkyl side chains which inhibited the growth of Gram-negative bacteria (Acinetobacter baumannii, Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa) at ∼1-4 μg mL-1 levels. They were found to be potent inhibitors of FPPS; cell growth was partially "rescued" by the addition of farnesol or overexpression of FPPS, and there was synergistic activity with known isoprenoid biosynthesis pathway inhibitors. Lipophilic hydroxyalkyl phosphonic acids inhibited UPPS and UPPP at micromolar levels; they were active (∼2-6 μg mL-1 ) against Gram-positive but not Gram-negative organisms, and again exhibited synergistic activity with cell wall biosynthesis inhibitors, but only indifferent effects with other inhibitors. The results are of interest because they describe novel inhibitors of FPPS, UPPS, and UPPP with cell growth inhibitory activities as low as ∼1-2 μg mL-1 .

Elucidating pharmacodynamic interaction of silver nanoparticle - topical deliverable antibiotics.

In order to exploit the potential benefits of antimicrobial combination therapy, we need a better understanding of the circumstances under which pharmacodynamic interactions expected. In this study, Pharmacodynamic interactions between silver nanoparticle (SNP) and topical antibiotics such as Cefazolin (CEF), Mupirocin (MUP), Gentamycin (GEN), Neomycin (NEO), Tetracycline (TET), Vancomycin (VAN) were investigated using the MIC test, Combination assay followed by Fractional Inhibitory concentration Index and Agar well diffusion method. SNP + MUP, SNP + NEO, SNP + VAN combinations showed Synergism (SN) and SNP + CEF, SNP + GEN, SNP + TET showed Partial synergism (PS) against Staphylococcus aureus. Four combinations (SNP + CEF, SNP + MUP, SNP + GEN, SNP + VAN) showed SN, SNP + TET showed PS and Indifferent effect (ID) were observed for SNP + NEO against Pseudomonas aeruginosa. SN was observed for SNP + CEF, SNP + GEN, SNP + NEO, SNP + TET and SNP + MUP showed ID, SNP + VAN showed PS against Escherichia coli. In addition, we elucidated the possible mechanism involved in the pharmacodynamic interaction between SNP-topical antibiotics by increased ROS level, membrane damage following protein release, K+ leakage and biofilm inhibition. Thus, our findings support that conjugation of the SNP with topical antibiotics have great potential in the topical formulation when treating complex resistant bacterial infections and where there is a need of more concentration to kill pathogenic bacteria.

Antibacterial activity and interactions of plant essential oil combinations against Gram-positive and Gram-negative bacteria

The aim of this study was to compare the antibacterial effects of several essential oils (EOs) alone and in combination against different Gram-positive and Gram-negative bacteria associated with food products. Parsley, lovage, basil, and thyme EOs, as well as their mixtures (1:1, v/v), were tested against Bacillus cereus, Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Salmonella typhimurium. The inhibitory effects ranged from strong (thyme EO against E. coli) to no inhibition (parsley EO against P. aeruginosa). Thyme EO exhibited strong (against E. coli), moderate (against S. typhimurium and B. cereus), or mild inhibitory effects (against P. aeruginosa and S. aureus), and basil EO showed mild (against E. coli and B. cereus) or no inhibitory effects (against S. typhimurium, P. aeruginosa, and S. aureus). Parsley and lovage EOs revealed no inhibitory effects against all tested strains. Combinations of lovage/thyme and basil/thyme EOs displayed antagonistic effects against all bacteria, parsley/thyme EOs against B. cereus, S. aureus, P. aeruginosa, and E. coli, and lovage/basil EOs against B. cereus and E. coli. Combinations of parsley/lovage and parsley/basil EOs exhibited indifferent effects against all bacteria. The combination of lovage/basil EO showed indifferent effect against S. aureus, P. aeruginosa, and S. typhimurium, and the combination parsley/thyme EO against S. typhimurium. Thyme EO has the highest percentage yield and antibacterial potential from all tested formulations; its combination with parsley, lovage, and basil EOs determines a reduction of its antibacterial activity. Hence, it is recommended to be used alone as the antibacterial agent.

Administration of Zinc Chelators Improves Survival of Mice Infected with Aspergillus fumigatus both in Monotherapy and in Combination with Caspofungin.

Aspergillus fumigatus can infect immunocompromised patients, leading to high mortality rates due to the lack of reliable treatment options. This pathogen requires uptake of zinc from host tissues in order to successfully grow and cause virulence. Reducing the availability of that micronutrient could help treat A. fumigatus infections. In this study, we examined the in vitro effects of seven chelators using a bioluminescent strain of A. fumigatus 1,10-Phenanthroline and N,N,N',N'-tetrakis(2-pyridylmethyl)ethane-1,2-diamine (TPEN) proved to be the chelators most effective at inhibiting fungal growth. Intraperitoneal administration of either phenanthroline or TPEN resulted in a significant improvement in survival and decrease of weight loss and fungal burden for immunosuppressed mice intranasally infected with A. fumigatus In vitro both chelators had an indifferent effect when employed in combination with caspofungin. The use of TPEN in combination with caspofungin also significantly increased survival compared to that when using these drugs individually. Our results suggest that zinc chelation may be a valid strategy for dealing with A. fumigatus infections and that both phenanthroline and TPEN could potentially be used either independently or in combination with caspofungin, indicating that their use in combination with other antifungal treatments might also be applicable.

Effects of essential oil combinations on pathogenic yeasts and moulds.

Essential oils (EOs) can be used as alternative or complementary antifungal agents against human pathogenic moulds and yeasts. To reduce the effective dose of antimicrobial agents, EOs are combined which can lead to synergistic or additive effect. In this study the anti-yeast and anti-mould activities of selected EOs were investigated, alone and in combinations, against clinical isolates of Candida albicans, C. parapsilosis, Aspergillus fumigatus, A. terreus, Rhizopus microsporus, Fusarium solani and Lichtheimia corymbifera. Minimum inhibitory concentrations (MICs) were determined for the EOs of cinnamon, citronella, clove, spearmint and thyme. To investigate the combination effect of the EOs, fractional inhibitory concentrations (FICs) were defined by the checkerboard method and the type of interaction was determined by the FIC index (FICI). FIC index below 0.5 was considered as synergism and between 0.5 and 1 as additive effect. Strongest antifungal activity was showed by thyme EO with MIC values below 1.0 mg/ml. Combination of EOs resulted in additive or indifferent effect, with occasional "borderline synergism". The best combination was cinnamon with clove leading to additive effect in all cases.