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 and 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 42K and 86Rubidium (86Rb) as tracers. 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 prevented 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 inhibition of K(+)-transport, with only one of four well-characterised K(+)-transport system mutants of Escherichia coli, namely Kup, being affected 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 agents.
Department of Immunology, University of Pretoria, Republic of South Africa.
E E
EE
De Bruyn
H C
HC
Steel
E J
EJ
Van Rensburg
R
R
Anderson
D000255:Adenosine Triphosphate / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002991:Clofazimine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000378:metabolism; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000378:metabolism*; D008244:Lysophosphatidylcholines / Q000378:metabolism / Q000494:pharmacology; D008246:Lysophospholipids / Q000378:metabolism* / Q000494:pharmacology; D009154:Mutation; D011188:Potassium / Q000378:metabolism* / Q000493:pharmacokinetics; D011197:Potassium Radioisotopes / Q000493:pharmacokinetics; D012414:Rubidium Radioisotopes / Q000493:pharmacokinetics; D014810:Vitamin E / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D008244:Lysophosphatidylcholines; D008246:Lysophospholipids; D011197:Potassium Radioisotopes; D012414:Rubidium Radioisotopes; D014810:Vitamin E; C030428:B 669; D000255:Adenosine Triphosphate; D002991:Clofazimine; D011188:Potassium