THE RIMINOPHENAZINES, CLOFAZIMINE AND B669, INHIBIT POTASSIUM-TRANSPORT IN GRAM-POSITIVE BACTERIA BY A LYSOPHOSPHOLIPID-DEPENDENT MECHANISM

The effects of the riminophenazine antimicrobial agents clofazimine an d B669 as well as those of lysophosphatidylcholine (LPC), on microbial K+-transporting systems were investigated in a range of Gram-positive and Gram-negative bacteria using K-42 and (86)Rubidium (Rb-86) as tra cers. Exposing the Gram-positive bacteria to 0.1-10 mg/L of the drugs resulted in a dose-related inhibition of uptake of both radiolabelled cations due primarily to the inhibition of their influx which was prev ented by pretreating the microorganisms with 25 mg/L alpha-tocopherol (vitamin E) which forms a complex with lysophospholipids. In contrast, Gram-negative bacteria were resistant to riminophenazine-mediated inh ibition of K+-transport, with only one of four well-characterised K+-t ransport system mutants of Escherichia coli, namely Kup, being affecte d by the antimicrobial agents. The selective antimicrobial activity of riminophenazines against Gram-positive bacteria is probably achieved by lysophospholipid-mediated inactivation of K+-transport, while Gram- negative microorganisms possess several K+-transport systems which are either inaccessible and/or insensitive to lysophospholipids. Thus, K-transport systems may represent novel targets for antimicrobial agent s.