BACTERIAL LIPOPOLYSACCHARIDE CONFERS RESISTANCE TO G418, DOXORUBICIN,AND TAXOL IN THE MURINE MACROPHAGE CELL-LINE, RAW264

Many bacterial pathogens including Salmonella and Listeria replicate w ithin macrophages. The susceptibility of these organisms to various an tibiotics is dependent on the ability of macrophages to take up, retai n, and deliver the antibiotic to the correct intracellular compartment . In this context, macrophages are known to express proteins that are involved in efflux of antibiotics and cytotoxic drugs, thereby reducin g intracellular accumulation of such compounds, In our studies on the action of bacterial lipopolysaccharide (LPS) on the macrophage-like ce ll line, RAW264 we found that LPS treatment of these cells conferred r esistance to the neomycin-related aminoglycoside G418 (geneticin). Thi s phenotype was stable and was specific to LPS since colony-stimulatin g factor 1 and phorbol myristate acetate had no effect on G418 resista nce. We have extended this observation to show that LPS induces transi ent resistance to the cytotoxic drugs taxol and doxorubicin. Macrophag e resistance to cytotoxic drugs and antibiotics may have a number of i mportant clinical consequences.