Development of a bacterial model for studying anthracycline-membrane interactions.
Growth of wild-type Escherichia coli strain MRE600 was severely affected up to 9 h following treatment with the anthracycline doxorubicin (15 microM), however, after 9 h, the cells became resistant. The onset of resistance coincided with some changes in the relative proportions of total saturated, monounsaturated and cyclopropane fatty acids. The anionic lipid content in E. coli strain HDL11 is under lac control and synthesis can be induced by incubation with the lac inducer IPTG. HDL11, with low levels of anionic phospholipid, was unaffected by doxorubicin (100 microM) over 9 h, with only slight inhibition of growth seen over 24 h. When the anionic lipid content of HDL11 was increased, there was a slight increase in the efficacy of doxorubicin, providing evidence for a membrane-based step in doxorubicin action.
Burrow
S M
SM
Department of Applied Biology, University of Central Lancashire, Preston, UK.
Rolph
C E
CE
Phoenix
D A
DA
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D004926:Escherichia coli / Q000187:drug effects* / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D007544:Isopropyl Thiogalactoside / Q000494:pharmacology; D010743:Phospholipids / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D005227:Fatty Acids; D010743:Phospholipids; D007544:Isopropyl Thiogalactoside; D004317:Doxorubicin