Multidrug resistance: Versatile drug sensors of bacterial cells

Lewis, Kim

doi:10.1016/s0960-9822(99)80254-1

Cited by 47 publications

(39 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results are in agreement with this report, indicating that berberine is rapidly transferred from blood into liver and bile through the active transportation in rats. Previously, several in vitro studies have shown that berberine is correlated to a certain degree with the multidrug resistance transporter, P-gp (Lin et al, 1999a;Lewis, 1999). In addition, several studies have also indicated that P-gp may play a transportation role in excreting some drugs from the liver into bile (Meijer et al, 1997;Kusuhara et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, berberine could antagonize the action of paclitaxel, a well known P-gp substrate in tumor cells mediated by MDR1 expression and thereby reduce its uptake and resistance (Lin et al, 1999b). Furthermore, there have been reports indicating that plant amphipathic cations, like berberine alkaloids, are good MDR substrates (Hsieh et al, 1998;Lewis, 1999). Since berberine interacts with the P-gp, clarification of the transport mechanism may provide important information for studying the pharmacokinetics of berberine.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Hepatobiliary Excretion of Berberine

Tsai¹,

Tsai²

2004

Drug Metab Dispos

143

View full text Add to dashboard Cite

This article is available online at http://dmd.aspetjournals.org ABSTRACT:Berberine is a bioactive herbal ingredient isolated from the roots and bark of Berberis aristata or Coptis chinensis. To investigate the detailed pharmacokinetics of berberine and its mechanisms of hepatobiliary excretion, an in vivo microdialysis coupled with highperformance liquid chromatography was performed. In the control group, rats received berberine alone; in the drug-treated group, 10 min before berberine administration, the rats were injected with cyclosporin A (CsA), a P-glycoprotein (P-gp) inhibitor; quinidine, both organic cation transport (OCT) and P-gp inhibitors; SKF-525A (proadifen), a cytochrome P450 inhibitor; and probenecid to inhibit the glucuronidation. The results indicate that berberine displays a linear pharmacokinetic phenomenon in the dosage range from 10 to 20 mg kg ؊1, since a proportional increase in the area under the concentration-time curve (AUC) of berberine was observed in this dosage range. Moreover, berberine was processed through hepatobiliary excretion against a concentration gradient based on the bile-to-blood distribution ratio (AUC bile /AUC blood ); the active berberine efflux might be affected by P-gp and OCT since coadministration of berberine and CsA or quinidine at the same dosage of 10 mg kg ؊1 significantly decreased the berberine amount in bile. In addition, berberine was metabolized in the liver with phase I demethylation and phase II glucuronidation, as identified by liquid chromatography/tandem mass spectrometry. Also, the phase I metabolism of berberine was partially reduced by SKF-525A treatment, but the phase II glucuronidation of berberine was not obviously affected by probenecid under the present study design.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Hepatobiliary Excretion of Berberine

Tsai¹,

Tsai²

2004

Drug Metab Dispos

143

View full text Add to dashboard Cite

show abstract

“…This situation is at odds with the widespread distribution of MDR transporters (42), which suggests that these transporters are likely to have important physiological functions related to the export of unidentified substrates encountered in the normal environment of each organism. Although the ability of QacA to efflux palmatine, nitidine, avicin, and chelerythrine has yet to be investigated, at the very least, berberine is likely to represent a natural MDR substrate, as this plant alkaloid is a substrate of both the plasmid-encoded QacA and also the chromosomally encoded NorA S. aureus MDR pumps (10)(11)(12). Taken together, these findings are suggestive of a preexisting role for the QacA-QacR system in providing resistance to plant and other naturally occurring, cationic and hydrophobic, antimicrobial compounds.…”

Section: Discussionmentioning

confidence: 99%

“…Attempts to answer the second of the above questions has led to the identification of natural substrates for several MDR transporters (7,(10)(11)(12)(13)(14). Although this represents an important first step, it must also be established whether the regulatory mechanisms governing the expression of the exporter in question mediate increased transporter production in response to the presence of these "physiological" substrates.…”

Section: Multidrug Resistance (Mdr)mentioning

confidence: 99%

Interactions of the QacR Multidrug-Binding Protein with Structurally Diverse Ligands: Implications for the Evolution of the Binding Pocket

et al. 2003

View full text Add to dashboard Cite

The QacR multidrug-binding repressor protein regulates the expression of the Staphylococcus aureus qacA gene, a multidrug resistance (MDR) locus that is prevalent in clinical isolates of this important human pathogen. In this paper we demonstrate that the range of structurally diverse compounds capable of inducing qacA transcription is significantly more varied than previously appreciated, particularly in relation to bivalent cations. For all of the newly identified inducing compounds, induction of qacA expression was correlated with a matching ability to dissociate QacR from operator DNA. Development of a ligand-binding assay based on intrinsic tryptophan fluorescence permitted dissociation constants to be determined for the majority of known QacR ligands, with values ranging from 0.2 to 82 µM. Highaffinity binding of a compound to QacR in vitro was not found to correlate very strongly with either its in vivo inducing abilities or its structure. The latter observation indicated that the QacR ligand-binding pocket appears to have evolved to accommodate a wide range of toxic hydrophobic cations, rather than a specific class of compound. Importantly, the antimicrobial ligands of QacR included several plant alkaloids that share structural similarities with synthetic MDR substrates. This is consistent with the suggestion that the qacA-qacR MDR locus was recently derived from genes that protect against natural antimicrobial compounds.

show abstract

“…Several natural compounds with anti-mycobacterium activity have been described from plants, fungi and marine organisms [6,7].…”

Section: Introductionmentioning

confidence: 99%

Anti-mycobacterial Activity of Selected Indian Botanicals Using Surrogate Mycobacterium Strains

Ng¹,

Dj²

2017

Nat Prod Chem Res

View full text Add to dashboard Cite

The aim of the present study was to validate the traditional claims of selected botanicals such as as Amorphophyllus sylvaticus, Andrographis paniculata, Corallocarpus epigaeus, Dioscorea bulbiferaand Morinda citrifolia (L) as possible inhibitors of Mycobacterial strains. Different solvent extracts along with flavonoid and alkaloid fractions of the selected ten medicinal plants were evaluated for their antimycobacterial activity against Mycobacterium smegmatis (NCIM 5138) and Mycobacterium phlei (NCIM 2240). The minimum inhibitory concentrations (MICs) were calculated for determining the efficacy of the selected botanicals. As a measure of quality control, High Performance Thin Layer Chromatography (HPTLC) fingerprint of flavonoids and alkaloids of the selected plants were also developed and the R f values of individual samples were recorded. Amongst the tested plants only Andrographis paniculata, Morinda citrifolia, and Enicostema axillare were observed to be effective growth inhibitors of selected less virulent Mycobacterium strains, however the chloroform extract of A. paniculata was observed to be most effective growth inhibitor of M. smegmatis (MIC=10 mg/ml) and M. phlei (MIC=10 mg/ml). The results of the present study revealed that the botanicals like Andrographis paniculata, Morinda citrifolia, and Enicostema axillare can be considered as an important resource for the identification of novel leads against Mycobacterial strains, which perhaps can be further explored for the management of multi drug resistance in treating tuberculosis.

show abstract

Multidrug resistance: Versatile drug sensors of bacterial cells

Cited by 47 publications

References 14 publications

Hepatobiliary Excretion of Berberine

Hepatobiliary Excretion of Berberine

Interactions of the QacR Multidrug-Binding Protein with Structurally Diverse Ligands: Implications for the Evolution of the Binding Pocket

Anti-mycobacterial Activity of Selected Indian Botanicals Using Surrogate Mycobacterium Strains

Contact Info

Product

Resources

About