A Method for Testing for Synergy with Any Number of Agents

Berenbaum, M. C.

doi:10.1093/infdis/137.2.122

Cited by 639 publications

(486 citation statements)

References 13 publications

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“…Three independent replicates were performed for each strain on separate days. Synergy of anhydrotetracycline and tetracycline combinations was determined using the fractional inhibitory concentration index (FICI) method 60 ,…”

Section: Methodsmentioning

confidence: 99%

Plasticity, dynamics, and inhibition of emerging tetracycline resistance enzymes

et al. 2017

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While tetracyclines are an important class of antibiotics in agriculture and the clinic, their efficacy is threatened by increasing resistance. Resistance to tetracyclines can occur through efflux, ribosomal protection, or enzymatic inactivation. Surprisingly, tetracycline enzymatic inactivation has remained largely unexplored despite providing the distinct advantage of antibiotic clearance. The tetracycline destructases are a recently-discovered family of tetracycline-inactivating flavoenzymes from pathogens and soil metagenomes with a high potential for broad dissemination. Here, we show tetracycline destructases accommodate tetracycline-class antibiotics in diverse and novel orientations for catalysis, and antibiotic binding drives unprecedented structural dynamics facilitating tetracycline inactivation. We identify a key inhibitor binding mode that locks the flavin adenine dinucleotide cofactor in an inactive state, functionally rescuing tetracycline activity. Our results reveal the potential of a novel tetracycline/tetracycline destructase inhibitor combination therapy strategy to overcome resistance by enzymatic inactivation and restore the use of an important class of antibiotics.

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Section: Methodsmentioning

confidence: 99%

Plasticity, dynamics, and inhibition of emerging tetracycline resistance enzymes

et al. 2017

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“…Following the procedure described by Berenbaum (1978), various combination mixtures of the extract and chloroquine (different ratio: 5:0, 4:1, 3:2, 2.5:2.5, 2:3, 1:4 and 0:5 of their respective IC 50 s determined beforehand) were tested using 96-well microtiter plates. Each combined solution was tested in duplicate in two independent experiments.…”

Section: Drug Interaction Assaymentioning

confidence: 99%

In vitro evaluation of antiplasmodial activity of extracts of Acanthospermum hispidum dc (Asteraceae) and Ficus thonningii blume (moraceae), two plants used in traditional medicine in the republic of Congo

Koukouikila-Koussounda¹,

Abena²,

Nzoungani³

et al. 2013

Afr. J. Trad. Compl. Alt. Med.

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The aim of this study was to evaluate extracts from two medicinal plants, Acanthospermum hispidum and Ficus thonningii, used in traditional medicine in Congo Brazzaville, for in vitro antiplasmodial activities against two laboratory strains of Plasmodium falciparum: the chloroquine sensitive 3D7 and the chloroquine resistant Dd2. ELISA HRP2 assay was used to evaluate the in vitro inhibitory activity of the extracts alone or in combination with chloroquine. Cytotoxicity was assessed on human HeLa cell line and reflected by the selectivity index. Methanolic extract of Acanthospermum hispidum exhibited a strong and a moderate inhibitory activity on the growth of Dd2 and 3D7 at 2.8 µg/ml and 9.2 µg/ml concentrations respectively with a selectivity index >10. The combination of the most active extract (methanolic extract of Acanthospermum hispidum) with chloroquine showed a synergistic interaction on both strains. The good selectivity index of Acanthospermum hispidum on HeLa cells reflects the safety of this plant. Extracts from Ficus thonningii did not show any promising antiplasmodial activity on both 3D7 and Dd2. Except the methanolic extract which exhibited a slight antiplasmodial activity with inhibitory concentration and selectivity index corresponding to 9.61 µg/ml and 11.16 respectively. Methanolic extract of Acanthospermum hispidum exhibited moderate to high inhibitory activity on 3D7 and Dd2 laboratory strains and a synergistic antimalarial effect when combined with chloroquine. Ficus thonningii seems to have no antimalarial activity. Phytochemical analysis, in vivo investigations using animal models and later clinical trials in collaboration with traditional practitioners are necessary to clarify the potential antimalarial activity of both plants.

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“…Drugs were combined in 96 wells microtitration test plates at various fractions of their respective IC 50 . Results were expressed as the mean sums of the fractional inhibitory concentrations (FIC), defined as (IC 50 of drug A in mixture/IC 50 of drug A alone) + (IC 50 of drug B in mixture/IC 50 of drug B alone) for each fixed concentration (Berenbaum, 1978;Canfield et al, 1995). Three types of drug interaction were defined as follows: additivity, sum of FIC = 1; synergism, sum of FIC < 1; and antagonism, sum of FIC > 1 (Ringwald et al, 1999;Ankoachere et al 2005).…”

Section: Bioassaysmentioning

confidence: 99%

Blood schizontocidal activity of methylene blue in combination with antimalarials againstPlasmodium falciparum

et al. 2007

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Summary :Methylene blue (MB) is the oldest synthetic antimalarial. It is not used anymore as antimalarial but should be reconsidered. For this purpose we have measured its impact on both chloroquine sensitive and resistant Plasmodium strains. We showed that around 5 nM of MB were able to inhibit 50 % of the parasite growth in vitro and that late rings and early trophozoites were the most sensitive stages; while early rings, late trophozoites and schizonts were less sensitive. Drug interaction study following fractional inhibitory concentrations (FIC) method showed antagonism with amodiaquine, atovaquone, doxycycline, pyrimethamine; additivity with artemether, chloroquine, mefloquine, primaquine and synergy with quinine. These results confirmed the interest of MB that could be integrated in a new low cost antimalarial combination therapy. Résumé

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A Method for Testing for Synergy with Any Number of Agents

Cited by 639 publications

References 13 publications

Plasticity, dynamics, and inhibition of emerging tetracycline resistance enzymes

Plasticity, dynamics, and inhibition of emerging tetracycline resistance enzymes

<i>In vitro</i> evaluation of antiplasmodial activity of extracts of <i>Acanthospermum hispidum</i> dc (Asteraceae) and <i>Ficus thonningii</i> blume (moraceae), two plants used in traditional medicine in the republic of Congo

Blood schizontocidal activity of methylene blue in combination with antimalarials againstPlasmodium falciparum

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