Analysis of pfmdr1 and drug susceptibility in fresh isolates of Plasmodium falciparum from Subsaharan Africa
Resistance of Plasmodium falciparum to many therapeutic agents is an increasing problem in most endemic areas. The role of the mdr-like gene products of P. falciparum in resistance to quinoline-containing compounds is not clear. The purpose of this study was to further examine the role of pfmdr1 in...
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| Veröffentlicht in: | Molecular and biochemical parasitology 1995-11, Vol.74 (2), p.157-166 |
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| creator | Basco, Leonardo K. Bras, Jacques Le Rhoades, Zane Wilson, Craig M. |
| description | Resistance of
Plasmodium falciparum to many therapeutic agents is an increasing problem in most endemic areas. The role of the
mdr-like gene products of
P. falciparum in resistance to quinoline-containing compounds is not clear. The purpose of this study was to further examine the role of
pfmdr1 in drug resistance in fresh clinical isolates originating from Africa. Drug susceptibility testing (chloroquine, mefloquine, halofantrine and quinine) and a molecular analysis of
pfmdr1 was completed for 51 fresh clinical isolates. A statistical association between the chloroquine sensitivity phenotype and an intragenic allele of
pfmdr1 was noted at a position, amino acid 86, which was previously associated with chloroquine resistance. There was little variation in the other intragenic alleles previously associated with chloroquine resistance. No correlation between
pfmdr1 intragenic allelic variation and susceptibility to mefloquine, halofantrine or quinine was found. There was no association between gene copy number of
pfmdr1 and any drug resistant phenotype in an analysis of selected isolates. This, along with other data, suggests that mefloquine resistance may have arisen by two different mechanisms in African and Southeast Asian isolates. Much more variability in the polyasparaginated region of the
pfmdr1 gene was noted in this study than previously reported. In addition, fingerprint analysis using multiplex PCR revealed considerable genetic variability among these isolates. |
| doi_str_mv | 10.1016/0166-6851(95)02492-1 |
| format | Article |
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Plasmodium falciparum to many therapeutic agents is an increasing problem in most endemic areas. The role of the
mdr-like gene products of
P. falciparum in resistance to quinoline-containing compounds is not clear. The purpose of this study was to further examine the role of
pfmdr1 in drug resistance in fresh clinical isolates originating from Africa. Drug susceptibility testing (chloroquine, mefloquine, halofantrine and quinine) and a molecular analysis of
pfmdr1 was completed for 51 fresh clinical isolates. A statistical association between the chloroquine sensitivity phenotype and an intragenic allele of
pfmdr1 was noted at a position, amino acid 86, which was previously associated with chloroquine resistance. There was little variation in the other intragenic alleles previously associated with chloroquine resistance. No correlation between
pfmdr1 intragenic allelic variation and susceptibility to mefloquine, halofantrine or quinine was found. There was no association between gene copy number of
pfmdr1 and any drug resistant phenotype in an analysis of selected isolates. This, along with other data, suggests that mefloquine resistance may have arisen by two different mechanisms in African and Southeast Asian isolates. Much more variability in the polyasparaginated region of the
pfmdr1 gene was noted in this study than previously reported. In addition, fingerprint analysis using multiplex PCR revealed considerable genetic variability among these isolates.</description><identifier>ISSN: 0166-6851</identifier><identifier>EISSN: 1872-9428</identifier><identifier>DOI: 10.1016/0166-6851(95)02492-1</identifier><identifier>PMID: 8719157</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Africa South of the Sahara ; Alleles ; Animals ; Antimalarials - pharmacology ; Base Sequence ; Chloroquine ; Chloroquine - pharmacology ; Codon - genetics ; DNA Fingerprinting ; DNA, Protozoan - genetics ; DNA, Protozoan - isolation & purification ; Drug resistance ; Drug Resistance, Multiple - genetics ; Genes, Protozoan ; Genetic Variation ; Humans ; Malaria ; Malaria, Falciparum - drug therapy ; Malaria, Falciparum - parasitology ; Mefloquine ; Mefloquine - pharmacology ; Multiple drug resistant ; Phenotype ; Plasmodium falciparum ; Plasmodium falciparum - drug effects ; Plasmodium falciparum - genetics ; Plasmodium falciparum - isolation & purification</subject><ispartof>Molecular and biochemical parasitology, 1995-11, Vol.74 (2), p.157-166</ispartof><rights>1995</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c454t-61507b1ab74c7d0b7e17c01cb04ed63f9e839187aa6a5c2504b088de9727ee143</citedby><cites>FETCH-LOGICAL-c454t-61507b1ab74c7d0b7e17c01cb04ed63f9e839187aa6a5c2504b088de9727ee143</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/0166685195024921$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8719157$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Basco, Leonardo K.</creatorcontrib><creatorcontrib>Bras, Jacques Le</creatorcontrib><creatorcontrib>Rhoades, Zane</creatorcontrib><creatorcontrib>Wilson, Craig M.</creatorcontrib><title>Analysis of pfmdr1 and drug susceptibility in fresh isolates of Plasmodium falciparum from Subsaharan Africa</title><title>Molecular and biochemical parasitology</title><addtitle>Mol Biochem Parasitol</addtitle><description>Resistance of
Plasmodium falciparum to many therapeutic agents is an increasing problem in most endemic areas. The role of the
mdr-like gene products of
P. falciparum in resistance to quinoline-containing compounds is not clear. The purpose of this study was to further examine the role of
pfmdr1 in drug resistance in fresh clinical isolates originating from Africa. Drug susceptibility testing (chloroquine, mefloquine, halofantrine and quinine) and a molecular analysis of
pfmdr1 was completed for 51 fresh clinical isolates. A statistical association between the chloroquine sensitivity phenotype and an intragenic allele of
pfmdr1 was noted at a position, amino acid 86, which was previously associated with chloroquine resistance. There was little variation in the other intragenic alleles previously associated with chloroquine resistance. No correlation between
pfmdr1 intragenic allelic variation and susceptibility to mefloquine, halofantrine or quinine was found. There was no association between gene copy number of
pfmdr1 and any drug resistant phenotype in an analysis of selected isolates. This, along with other data, suggests that mefloquine resistance may have arisen by two different mechanisms in African and Southeast Asian isolates. Much more variability in the polyasparaginated region of the
pfmdr1 gene was noted in this study than previously reported. In addition, fingerprint analysis using multiplex PCR revealed considerable genetic variability among these isolates.</description><subject>Africa South of the Sahara</subject><subject>Alleles</subject><subject>Animals</subject><subject>Antimalarials - pharmacology</subject><subject>Base Sequence</subject><subject>Chloroquine</subject><subject>Chloroquine - pharmacology</subject><subject>Codon - genetics</subject><subject>DNA Fingerprinting</subject><subject>DNA, Protozoan - genetics</subject><subject>DNA, Protozoan - isolation & purification</subject><subject>Drug resistance</subject><subject>Drug Resistance, Multiple - genetics</subject><subject>Genes, Protozoan</subject><subject>Genetic Variation</subject><subject>Humans</subject><subject>Malaria</subject><subject>Malaria, Falciparum - drug therapy</subject><subject>Malaria, Falciparum - parasitology</subject><subject>Mefloquine</subject><subject>Mefloquine - pharmacology</subject><subject>Multiple drug resistant</subject><subject>Phenotype</subject><subject>Plasmodium falciparum</subject><subject>Plasmodium falciparum - drug effects</subject><subject>Plasmodium falciparum - genetics</subject><subject>Plasmodium falciparum - isolation & purification</subject><issn>0166-6851</issn><issn>1872-9428</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1995</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkV1LHDEUhkOp6Gr7DyrkqtSLsTmz-bwRFmlVECy0vQ6Z5ExNmS-TmcL--2bdxUu9CAmc5z3hPIeQT8AugYH8Wo6spBbwxYgLVnNTV_COrECrujK81u_J6gU5Iac5_2WMCSXlMTnWCgwItSLdZnDdNsdMx5ZObR8SUDcEGtLyh-Yle5zm2MQuzlsaB9omzI805rFzMz5nfnQu92OIS09b1_k4ubR7prGnP5cmu0eX3EA3bYrefSBHhcn48XCfkd_fv_26vq3uH27urjf3leeCz5UEwVQDrlHcq8AahaA8A98wjkGuW4N6bcqYzkknfC0Yb5jWAY2qFSLw9Rn5vO87pfFpwTzbPpZJus4NOC7ZKqV18fA2CMLUoKUqIN-DPo05J2ztlGLv0tYCs7tt2J1qu1NtjbDP27BQYueH_kvTY3gJHfSX-tW-jsXGv4jJZh9x8BhiQj_bMMbXP_gPHemZ8w</recordid><startdate>19951101</startdate><enddate>19951101</enddate><creator>Basco, Leonardo K.</creator><creator>Bras, Jacques Le</creator><creator>Rhoades, Zane</creator><creator>Wilson, Craig M.</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>M7N</scope><scope>7X8</scope></search><sort><creationdate>19951101</creationdate><title>Analysis of pfmdr1 and drug susceptibility in fresh isolates of Plasmodium falciparum from Subsaharan Africa</title><author>Basco, Leonardo K. ; Bras, Jacques Le ; Rhoades, Zane ; Wilson, Craig M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c454t-61507b1ab74c7d0b7e17c01cb04ed63f9e839187aa6a5c2504b088de9727ee143</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1995</creationdate><topic>Africa South of the Sahara</topic><topic>Alleles</topic><topic>Animals</topic><topic>Antimalarials - pharmacology</topic><topic>Base Sequence</topic><topic>Chloroquine</topic><topic>Chloroquine - pharmacology</topic><topic>Codon - genetics</topic><topic>DNA Fingerprinting</topic><topic>DNA, Protozoan - genetics</topic><topic>DNA, Protozoan - isolation & purification</topic><topic>Drug resistance</topic><topic>Drug Resistance, Multiple - genetics</topic><topic>Genes, Protozoan</topic><topic>Genetic Variation</topic><topic>Humans</topic><topic>Malaria</topic><topic>Malaria, Falciparum - drug therapy</topic><topic>Malaria, Falciparum - parasitology</topic><topic>Mefloquine</topic><topic>Mefloquine - pharmacology</topic><topic>Multiple drug resistant</topic><topic>Phenotype</topic><topic>Plasmodium falciparum</topic><topic>Plasmodium falciparum - drug effects</topic><topic>Plasmodium falciparum - genetics</topic><topic>Plasmodium falciparum - isolation & purification</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Basco, Leonardo K.</creatorcontrib><creatorcontrib>Bras, Jacques Le</creatorcontrib><creatorcontrib>Rhoades, Zane</creatorcontrib><creatorcontrib>Wilson, Craig M.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular and biochemical parasitology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Basco, Leonardo K.</au><au>Bras, Jacques Le</au><au>Rhoades, Zane</au><au>Wilson, Craig M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Analysis of pfmdr1 and drug susceptibility in fresh isolates of Plasmodium falciparum from Subsaharan Africa</atitle><jtitle>Molecular and biochemical parasitology</jtitle><addtitle>Mol Biochem Parasitol</addtitle><date>1995-11-01</date><risdate>1995</risdate><volume>74</volume><issue>2</issue><spage>157</spage><epage>166</epage><pages>157-166</pages><issn>0166-6851</issn><eissn>1872-9428</eissn><abstract>Resistance of
Plasmodium falciparum to many therapeutic agents is an increasing problem in most endemic areas. The role of the
mdr-like gene products of
P. falciparum in resistance to quinoline-containing compounds is not clear. The purpose of this study was to further examine the role of
pfmdr1 in drug resistance in fresh clinical isolates originating from Africa. Drug susceptibility testing (chloroquine, mefloquine, halofantrine and quinine) and a molecular analysis of
pfmdr1 was completed for 51 fresh clinical isolates. A statistical association between the chloroquine sensitivity phenotype and an intragenic allele of
pfmdr1 was noted at a position, amino acid 86, which was previously associated with chloroquine resistance. There was little variation in the other intragenic alleles previously associated with chloroquine resistance. No correlation between
pfmdr1 intragenic allelic variation and susceptibility to mefloquine, halofantrine or quinine was found. There was no association between gene copy number of
pfmdr1 and any drug resistant phenotype in an analysis of selected isolates. This, along with other data, suggests that mefloquine resistance may have arisen by two different mechanisms in African and Southeast Asian isolates. Much more variability in the polyasparaginated region of the
pfmdr1 gene was noted in this study than previously reported. In addition, fingerprint analysis using multiplex PCR revealed considerable genetic variability among these isolates.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>8719157</pmid><doi>10.1016/0166-6851(95)02492-1</doi><tpages>10</tpages></addata></record> |
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| issn | 0166-6851 1872-9428 |
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| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | Africa South of the Sahara Alleles Animals Antimalarials - pharmacology Base Sequence Chloroquine Chloroquine - pharmacology Codon - genetics DNA Fingerprinting DNA, Protozoan - genetics DNA, Protozoan - isolation & purification Drug resistance Drug Resistance, Multiple - genetics Genes, Protozoan Genetic Variation Humans Malaria Malaria, Falciparum - drug therapy Malaria, Falciparum - parasitology Mefloquine Mefloquine - pharmacology Multiple drug resistant Phenotype Plasmodium falciparum Plasmodium falciparum - drug effects Plasmodium falciparum - genetics Plasmodium falciparum - isolation & purification |
| title | Analysis of pfmdr1 and drug susceptibility in fresh isolates of Plasmodium falciparum from Subsaharan Africa |
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