Development of a bacterial model for studying anthracycline-membrane interactions

Abstract

Growth of wild-type Escherichiu coli strain MRE600 was severely affected up to 9 h following treatment with the anthracycline doxorubicin (15 FM), 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 HDLl 1 is under luc control and synthesis can be induced by incubation with the Zuc inducer IFTG. HDLl 1, with low levels of anionic phospholipid, was unaffected by doxorubicin (100 FM) over 9 h, with only slight inhibition of growth seen over 24 h. When the anionic lipid content of HDLll was increased, there was a slight increase in the efficacy of doxorubicin, providing evidence for a membrane-based step in doxorubicin action.