Chemotherapy and drug resistance in malaria

Cowman, Alan F.; Foote, Simon J.

doi:10.1016/0020-7519(90)90198-v

Cited by 60 publications

(29 citation statements)

References 78 publications

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“…However, single-(N 108 ) and doublemutant (I 51 N 108 ) dhfr genotypes were less prevalent at 1.14% and 32.95%, respectively, whereas the triple mutant (I 51 R 59 N 108 ) associated with high-level pyrimethamine resistance 29,30 was not seen in the region (Tables 1 and 2).…”

Section: Resultsmentioning

confidence: 99%

Distribution of Drug Resistance Genotypes in Plasmodium falciparum in an Area of Limited Parasite Diversity in Saudi Arabia

Dajem

Al-Farsi

Al-Hashami

et al. 2012

The American Society of Tropical Medicine and Hygiene

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Section: Resultsmentioning

confidence: 99%

Distribution of Drug Resistance Genotypes in Plasmodium falciparum in an Area of Limited Parasite Diversity in Saudi Arabia

Dajem

Al-Farsi

Al-Hashami

et al. 2012

The American Society of Tropical Medicine and Hygiene

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“…Each type of ABC transporter may thus adopt a different regulatory pattern. In K. lactis, because both positive and negative regulation are observed in sit4 mutants, it can be imagined that more than one pathway operates to achieve the regulation of individual transporters by 5 G. D. Clark-Walker, unpublished data. Sit4p.…”

Section: Figmentioning

confidence: 99%

“…These membrane proteins, known as ATP-binding cassette (ABC) transporters, function in an ATP-dependent way probably by increasing drug efflux and consequently lowering their intracellular accumulation. In a similar manner, many pathogenic microorganisms such as Candida albicans and Plasmodium falciparum can use the ABC transporter-mediated drug efflux mechanism to evade chemotherapy (5)(6)(7)(8). However, despite the rapidly growing number of ABC transporters identified in various organisms, little is known about how activities of the drug transporters are modulated and how aberrant regulation of the expression of ABC transporter genes contributes to the acquisition of MDR in vivo.…”

mentioning

confidence: 99%

Positive and Negative Control of Multidrug Resistance by the Sit4 Protein Phosphatase in Kluyveromyces lactis

Chen¹,

Bauer²,

Kuchler³

et al. 2000

Journal of Biological Chemistry

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The nuclear gene encoding the Sit4 protein phosphatase was identified in the budding yeast Kluyveromyces lactis. K. lactis cells carrying a disrupted sit4 allele are resistant to oligomycin, antimycin, ketoconazole, and econazole but hypersensitive to paromomycin, sorbic acid, and 4-nitroquinoline-N-oxide (4-NQO). Overexpression of SIT4 leads to an elevation in resistance to paromomycin and to lesser extent tolerance to sorbic acid, but it has no detectable effect on resistance to 4-NQO. These observations suggest that the Sit4 protein phosphatase has a broad role in modulating multidrug resistance in K. lactis. Expression or activity of a membrane transporter specific for paromomycin and the ABC pumps responsible for 4-NQO and sorbic acid would be positively regulated by Sit4p. In contrast, the function of a Pdr5-type transporter responsible for ketoconazole and econazole extrusion, and probably also for efflux of oligomycin and antimycin, is likely to be negatively regulated by the phosphatase. Drug resistance of sit4 mutants was shown to be mediated by ABC transporters as efflux of the anionic fluorescent dye rhodamine 6G, a substrate for the Pdr5-type pump, is markedly increased in sit4 mutants in an energy-dependent and FK506-sensitive manner.The occurrence of multidrug resistance (MDR) 1 is one of the main obstacles to the successful treatment of cancer. When treated with chemotherapeutic drugs, many cancer cells develop resistance to a variety of structurally and functionally unrelated compounds (for review, see Ref. 1). In most cases, MDR is mediated by an increased expression of the integral membrane multidrug transporters (reviewed in Refs. 2-4). These membrane proteins, known as ATP-binding cassette (ABC) transporters, function in an ATP-dependent way probably by increasing drug efflux and consequently lowering their intracellular accumulation. In a similar manner, many pathogenic microorganisms such as Candida albicans and Plasmodium falciparum can use the ABC transporter-mediated drug efflux mechanism to evade chemotherapy (5-8). However, despite the rapidly growing number of ABC transporters identified in various organisms, little is known about how activities of the drug transporters are modulated and how aberrant regulation of the expression of ABC transporter genes contributes to the acquisition of MDR in vivo.The ABC transporter-mediated drug efflux mechanism is evolutionarily conserved and occurs in a variety of living organisms ranging from bacteria to humans. An example is a recent work demonstrating that the Lactococcus lactis ABC transporter LmrA is able to confer MDR in human cells (9). The recently completed genome sequencing project of Saccharomyces cerevisiae has revealed the presence of as many as 29 proteins belonging to the ubiquitous ABC superfamily (10) that transport a wide range of chemical compounds (11,12). The yeast ABC proteins so far characterized, such as Pdr5, Snq2, Ycf1 and Yor1, confer MDR with physiological and biochemical properties very similar to the human MDR1-en...

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“…Malaria Foundation International estimates that malaria causes up to 500 million clinical cases and over one million deaths each year; every 30 seconds, a child somewhere dies of malaria (Malaria Foundational International; http:// www.malaria.org). It is rare to find a country in which malaria is endemic where chloroquine resistance has not been reported, and although the 4-aminoquinolone chloroquine is the drug most often reported to be associated with resistance, multidrug resistance is rapidly increasing in prevalence (4,15,21). New antimalarial drugs are urgently needed to overcome drug resistance.…”

mentioning

confidence: 99%

Efficacy of Proton Pump Inhibitor Drugs against Plasmodium falciparum In Vitro and Their Probable Pharmacophores

Riel

Kyle

Bhattacharjee

et al. 2002

Antimicrob Agents Chemother

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The substituted benzimidazoles omeprazole, lansoprazole, rabeprazole, and pantoprazole were found to have in vitro activity against three different isolates of Plasmodium falciparum: D6 (which is chloroquine and pyrimethamine sensitive), W2 (chloroquine and pyrimethamine resistant), and TM91C235 (multidrug resistant). Lansoprazole and rabeprazole were the most effective against all three isolates, with a 50% inhibitory concentration (

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Chemotherapy and drug resistance in malaria

Cited by 60 publications

References 78 publications

Distribution of Drug Resistance Genotypes in Plasmodium falciparum in an Area of Limited Parasite Diversity in Saudi Arabia

Distribution of Drug Resistance Genotypes in Plasmodium falciparum in an Area of Limited Parasite Diversity in Saudi Arabia

Positive and Negative Control of Multidrug Resistance by the Sit4 Protein Phosphatase in Kluyveromyces lactis

Efficacy of Proton Pump Inhibitor Drugs against Plasmodium falciparum In Vitro and Their Probable Pharmacophores

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