Inhibition of Antibiotic Efflux in Bacteria by the Novel Multidrug Resistance Inhibitors Biricodar (VX-710) and Timcodar (VX-853)

Mullin, Steve; Mani, Nagraj; Grossman, Trudy H.

doi:10.1128/aac.48.11.4171-4176.2004

Cited by 94 publications

(68 citation statements)

References 32 publications

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“…Inhibitors of mammalian MDR transporters, such as reserpine, biricodar (VX-710), and timcodar (VX-853), increase the drug sensitivities of these strains. This global approach also demonstrated efflux-based resistance mechanisms to a number of antibiotics for three clinically significant gram-positive pathogens, Staphylococcus aureus, E. faecalis, and S. pneumoniae (93). Again, the molecular details of the resistance remain to be resolved.…”

Section: Streptococcus Pneumoniaementioning

confidence: 99%

Distribution and Physiology of ABC-Type Transporters Contributing to Multidrug Resistance in Bacteria

Lubelski

Konings

Driessen

2007

Microbiol Mol Biol Rev

282

188

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SUMMARY Membrane proteins responsible for the active efflux of structurally and functionally unrelated drugs were first characterized in higher eukaryotes. To date, a vast number of transporters contributing to multidrug resistance (MDR transporters) have been reported for a large variety of organisms. Predictions about the functions of genes in the growing number of sequenced genomes indicate that MDR transporters are ubiquitous in nature. The majority of described MDR transporters in bacteria use ion motive force, while only a few systems have been shown to rely on ATP hydrolysis. However, recent reports on MDR proteins from gram-positive organisms, as well as genome analysis, indicate that the role of ABC-type MDR transporters in bacterial drug resistance might be underestimated. Detailed structural and mechanistic analyses of these proteins can help to understand their molecular mode of action and may eventually lead to the development of new strategies to counteract their actions, thereby increasing the effectiveness of drug-based therapies. This review focuses on recent advances in the analysis of ABC-type MDR transporters in bacteria.

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Section: Streptococcus Pneumoniaementioning

confidence: 99%

Distribution and Physiology of ABC-Type Transporters Contributing to Multidrug Resistance in Bacteria

Lubelski

Konings

Driessen

2007

Microbiol Mol Biol Rev

282

188

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“…Efflux of antibiotics is a clinically important resistance mechanism for bacteria, often endowing them with multipledrug-resistance (MDR) phenotypes (13). Efflux pumps may be specific for one substrate or may transport various compounds with different structures (17).…”

Section: Introductionmentioning

confidence: 99%

Effect of galbanic acid, a sesquiterpene coumarin from Ferula szowitsiana, as an inhibitor of efflux mechanism in resistant clinical isolates of Staphylococcus aureus

Bazzaz¹,

Memariani²,

Khashiarmanesh³

et al. 2010

Braz. J. Microbiol.

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Galbanic acid, a sesquiterpene coumarin from Ferula szowitsiana roots, was investigated for its potentiating effect on the antimicrobial activity of antibiotics as well as ethidium bromide, in 6 multidrug resistance (MDR) clinical isolates of Staphylococcus aureus. Galbanic acid had inhibitory effect on none of the isolated bacteria tested (up to 800 µg /ml). The MIC range of ciprofloxacin, tetracycline and ethidium bromide, against all tested S. aureus were 10-80, 10-80 and 4-16 µg/ml, respectively. These were reduced to 2.5-5, 2.5-5 and 0.5-2 µg/ml in the presence of galbanic acid (300 µg /ml) or verapamil (100 µg /ml). The rate of ethidium bromide (2 µg /ml) accumulation in clinical isolates was enhanced with galbanic acid (300 µg /ml). There is also a decrease in loss of ethidium bromide from bacteria in the presence of galbanic acid. Similar results were obtained when verapamil (100 µg /ml) was used as an efflux pump inhibitor. Galbanic acid, like verapamil, a typical inhibitor of efflux pump, reduced the MIC of ethidium bromide and tested antibiotics. Since efflux is the only known reported mechanism for ethidium bromide resistance, the reduction in ethidium bromide MIC and enhanced accumulation as well as decreased efflux of ethidium bromide in the presence of galbanic acid, can be attributed to this efflux inhibitory properties.

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“…Our results on the anti-Pseudomonas activity of ()-epidihydropinidine are promising since gram-negative bacteria in general are more resistant to antibiotic agents than gram-positive bacteria due to the presence of an outer lipopolysaccharide (LPS) rich membrane which acts as a permeability barrier, especially for hydrophilic and negatively charged molecules [74,75,76,77,78]. We suggest that ()-epidihydropinidine, as a relatively hydrophilic water soluble molecule [79], is exerting its growth inhibitory effects on P. aeruginosa, and other gram-negative bacteria, by travelling through porins, water-filled channels in the outer lipopolysaccharide membrane and reaching possible target in periplasmic space or at inner cell membrane [80].…”

Section: Discussionmentioning

confidence: 99%

Epidihydropinidine, the main piperidine alkaloid compound of Norway spruce (Picea abies) shows promising antibacterial and anti-Candida activity

et al. 2017

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ArtikkelitLuonnontieteiden This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A C C E P T E D M A N U S C R I P T

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Inhibition of Antibiotic Efflux in Bacteria by the Novel Multidrug Resistance Inhibitors Biricodar (VX-710) and Timcodar (VX-853)

Cited by 94 publications

References 32 publications

Distribution and Physiology of ABC-Type Transporters Contributing to Multidrug Resistance in Bacteria

Distribution and Physiology of ABC-Type Transporters Contributing to Multidrug Resistance in Bacteria

Effect of galbanic acid, a sesquiterpene coumarin from Ferula szowitsiana, as an inhibitor of efflux mechanism in resistant clinical isolates of Staphylococcus aureus

Epidihydropinidine, the main piperidine alkaloid compound of Norway spruce (Picea abies) shows promising antibacterial and anti-Candida activity

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