The Mechanism of Overcoming Multidrug Resistance (MDR) of Fungi by Amphotericin B and Its Derivatives
Comparative studies were performed to determine the activity and cytotoxicity of amphotericin B (AmB) and its derivatives on standard strain of Saccharomyces cerevisiae and its transformants with cloned genes from Candida albicans encoding multidrug resistance (MDR) pumps of ATP-binding cassette and...
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| Veröffentlicht in: | Journal of antibiotics 2007-07, Vol.60 (7), p.436-446 |
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| creator | ślisz, Magdalena Cybulska, Barbara Grzybowska, Jolanta Czub, Jacek Prasad, Rajendra Borowski, Edward |
| description | Comparative studies were performed to determine the activity and cytotoxicity of amphotericin B (AmB) and its derivatives on standard strain of
Saccharomyces cerevisiae
and its transformants with cloned genes from
Candida albicans
encoding multidrug resistance (MDR) pumps of ATP-binding cassette and major facilitator superfamilies. The AmB derivatives: amphotericin B 3-dimethylaminopropyl amide and
N
-methyl-
N
-
D
-fructopyranosylamphotericin B methyl ester were shown to be fungistatic and fungicidal towards MDR strains, by membrane permeabilization mechanism. Antibiotic-cell interaction monitored by energy transfer method indicates similar membrane affinity in parent strain and its MDR transformants. Experiments with fungal cells loaded with rhodamine 6G point to lack of competition between this dye and AmB and its derivatives for efflux driven by CDR2p. It can be thus assumed that AmB and its derivatives overcome fungal MDR by not being substrates of the multidrug exporting pumps, presumably due to their large molecular volumes. |
| doi_str_mv | 10.1038/ja.2007.56 |
| format | Article |
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Saccharomyces cerevisiae
and its transformants with cloned genes from
Candida albicans
encoding multidrug resistance (MDR) pumps of ATP-binding cassette and major facilitator superfamilies. The AmB derivatives: amphotericin B 3-dimethylaminopropyl amide and
N
-methyl-
N
-
D
-fructopyranosylamphotericin B methyl ester were shown to be fungistatic and fungicidal towards MDR strains, by membrane permeabilization mechanism. Antibiotic-cell interaction monitored by energy transfer method indicates similar membrane affinity in parent strain and its MDR transformants. Experiments with fungal cells loaded with rhodamine 6G point to lack of competition between this dye and AmB and its derivatives for efflux driven by CDR2p. It can be thus assumed that AmB and its derivatives overcome fungal MDR by not being substrates of the multidrug exporting pumps, presumably due to their large molecular volumes.</description><identifier>ISSN: 0021-8820</identifier><identifier>EISSN: 1881-1469</identifier><identifier>DOI: 10.1038/ja.2007.56</identifier><identifier>PMID: 17721002</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Amphotericin B - analogs & derivatives ; Amphotericin B - pharmacokinetics ; Amphotericin B - pharmacology ; Antifungal Agents - pharmacokinetics ; Antifungal Agents - pharmacology ; ATP-Binding Cassette Transporters ; Bacteriology ; Bioorganic Chemistry ; Candida albicans ; Candida albicans - drug effects ; Candida albicans - genetics ; Comparative studies ; Cytotoxicity ; Drug Resistance, Multiple, Fungal - genetics ; Energy transfer ; Fungi ; Genes, Fungal - drug effects ; Genes, MDR - drug effects ; Humans ; Life Sciences ; Medicinal Chemistry ; Microbial Sensitivity Tests ; Microbiology ; Organic Chemistry ; original-article ; Pumps ; Saccharomyces cerevisiae ; Saccharomyces cerevisiae - drug effects ; Saccharomyces cerevisiae - genetics ; Transformation, Genetic</subject><ispartof>Journal of antibiotics, 2007-07, Vol.60 (7), p.436-446</ispartof><rights>Japan Antibiotics Research Association 2007</rights><rights>Copyright Nature Publishing Group Jul 2007</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c445t-13ec8935b798135fc0e4ce5d45ed6804d3fcbba1d83b466d012c02f90c365a5d3</citedby><cites>FETCH-LOGICAL-c445t-13ec8935b798135fc0e4ce5d45ed6804d3fcbba1d83b466d012c02f90c365a5d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17721002$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>ślisz, Magdalena</creatorcontrib><creatorcontrib>Cybulska, Barbara</creatorcontrib><creatorcontrib>Grzybowska, Jolanta</creatorcontrib><creatorcontrib>Czub, Jacek</creatorcontrib><creatorcontrib>Prasad, Rajendra</creatorcontrib><creatorcontrib>Borowski, Edward</creatorcontrib><title>The Mechanism of Overcoming Multidrug Resistance (MDR) of Fungi by Amphotericin B and Its Derivatives</title><title>Journal of antibiotics</title><addtitle>J Antibiot</addtitle><addtitle>J Antibiot (Tokyo)</addtitle><description>Comparative studies were performed to determine the activity and cytotoxicity of amphotericin B (AmB) and its derivatives on standard strain of
Saccharomyces cerevisiae
and its transformants with cloned genes from
Candida albicans
encoding multidrug resistance (MDR) pumps of ATP-binding cassette and major facilitator superfamilies. The AmB derivatives: amphotericin B 3-dimethylaminopropyl amide and
N
-methyl-
N
-
D
-fructopyranosylamphotericin B methyl ester were shown to be fungistatic and fungicidal towards MDR strains, by membrane permeabilization mechanism. Antibiotic-cell interaction monitored by energy transfer method indicates similar membrane affinity in parent strain and its MDR transformants. Experiments with fungal cells loaded with rhodamine 6G point to lack of competition between this dye and AmB and its derivatives for efflux driven by CDR2p. It can be thus assumed that AmB and its derivatives overcome fungal MDR by not being substrates of the multidrug exporting pumps, presumably due to their large molecular volumes.</description><subject>Amphotericin B - analogs & derivatives</subject><subject>Amphotericin B - pharmacokinetics</subject><subject>Amphotericin B - pharmacology</subject><subject>Antifungal Agents - pharmacokinetics</subject><subject>Antifungal Agents - pharmacology</subject><subject>ATP-Binding Cassette Transporters</subject><subject>Bacteriology</subject><subject>Bioorganic Chemistry</subject><subject>Candida albicans</subject><subject>Candida albicans - drug effects</subject><subject>Candida albicans - genetics</subject><subject>Comparative studies</subject><subject>Cytotoxicity</subject><subject>Drug Resistance, Multiple, Fungal - genetics</subject><subject>Energy transfer</subject><subject>Fungi</subject><subject>Genes, Fungal - drug effects</subject><subject>Genes, MDR - drug effects</subject><subject>Humans</subject><subject>Life Sciences</subject><subject>Medicinal Chemistry</subject><subject>Microbial Sensitivity Tests</subject><subject>Microbiology</subject><subject>Organic Chemistry</subject><subject>original-article</subject><subject>Pumps</subject><subject>Saccharomyces cerevisiae</subject><subject>Saccharomyces cerevisiae - 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Academic</collection><jtitle>Journal of antibiotics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>ślisz, Magdalena</au><au>Cybulska, Barbara</au><au>Grzybowska, Jolanta</au><au>Czub, Jacek</au><au>Prasad, Rajendra</au><au>Borowski, Edward</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Mechanism of Overcoming Multidrug Resistance (MDR) of Fungi by Amphotericin B and Its Derivatives</atitle><jtitle>Journal of antibiotics</jtitle><stitle>J Antibiot</stitle><addtitle>J Antibiot (Tokyo)</addtitle><date>2007-07-01</date><risdate>2007</risdate><volume>60</volume><issue>7</issue><spage>436</spage><epage>446</epage><pages>436-446</pages><issn>0021-8820</issn><eissn>1881-1469</eissn><abstract>Comparative studies were performed to determine the activity and cytotoxicity of amphotericin B (AmB) and its derivatives on standard strain of
Saccharomyces cerevisiae
and its transformants with cloned genes from
Candida albicans
encoding multidrug resistance (MDR) pumps of ATP-binding cassette and major facilitator superfamilies. The AmB derivatives: amphotericin B 3-dimethylaminopropyl amide and
N
-methyl-
N
-
D
-fructopyranosylamphotericin B methyl ester were shown to be fungistatic and fungicidal towards MDR strains, by membrane permeabilization mechanism. Antibiotic-cell interaction monitored by energy transfer method indicates similar membrane affinity in parent strain and its MDR transformants. Experiments with fungal cells loaded with rhodamine 6G point to lack of competition between this dye and AmB and its derivatives for efflux driven by CDR2p. It can be thus assumed that AmB and its derivatives overcome fungal MDR by not being substrates of the multidrug exporting pumps, presumably due to their large molecular volumes.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>17721002</pmid><doi>10.1038/ja.2007.56</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
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| ispartof | Journal of antibiotics, 2007-07, Vol.60 (7), p.436-446 |
| issn | 0021-8820 1881-1469 |
| language | eng |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Amphotericin B - analogs & derivatives Amphotericin B - pharmacokinetics Amphotericin B - pharmacology Antifungal Agents - pharmacokinetics Antifungal Agents - pharmacology ATP-Binding Cassette Transporters Bacteriology Bioorganic Chemistry Candida albicans Candida albicans - drug effects Candida albicans - genetics Comparative studies Cytotoxicity Drug Resistance, Multiple, Fungal - genetics Energy transfer Fungi Genes, Fungal - drug effects Genes, MDR - drug effects Humans Life Sciences Medicinal Chemistry Microbial Sensitivity Tests Microbiology Organic Chemistry original-article Pumps Saccharomyces cerevisiae Saccharomyces cerevisiae - drug effects Saccharomyces cerevisiae - genetics Transformation, Genetic |
| title | The Mechanism of Overcoming Multidrug Resistance (MDR) of Fungi by Amphotericin B and Its Derivatives |
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