Lactoferrin and transferrin damage of the gram-negative outer membrane is modulated by Ca2+ and Mg2+.
Lactoferrin and transferrin have antimicrobial activity against selected Gram-negative bacteria, but the mechanism of action has not been defined. We studied the ability of lactoferrin and transferrin to damage the Gram-negative outer membrane. Lipopolysaccharide release by the proteins could be blocked by concurrent addition of Ca2+ and Mg2+. Addition of Ca2+ also blocked the ability of lactoferrin to increase the susceptibility of Escherichia coli to rifampicin. Transferrin, but not lactoferrin, increased susceptibility of Gram-negative bacteria to deoxycholate, with reversal of sensitivity occurring with exposure to Ca2+ or Mg2+. In transmission electron microscopy studies polymyxin B caused finger-like membrane projections, but no morphological alterations were seen in cells exposed to EDTA, lactoferrin or transferrin. These data provide further evidence that lactoferrin and transferrin act as membrane-active agents with the effects modulated by Ca2+ and Mg2+.
Ellison
R T
RT
Medical Service, Department of Veterans Affairs Medical Center, Little Rock, Arkansas.
LaForce
F M
FM
Giehl
T J
TJ
Boose
D S
DS
Dunn
B E
BE
D002118:Calcium / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000648:ultrastructure; D003840:Deoxycholic Acid / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D004926:Escherichia coli / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000254:growth & development / Q000648:ultrastructure; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D007781:Lactoferrin / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000378:metabolism; D008274:Magnesium / Q000494:pharmacology*; D008854:Microscopy, Electron; D011112:Polymyxin B / Q000494:pharmacology; D012293:Rifampin / Q000494:pharmacology; D014168:Transferrin / Q000494:pharmacology*
D008070:Lipopolysaccharides; D014168:Transferrin; D003840:Deoxycholic Acid; D007781:Lactoferrin; D008274:Magnesium; D011112:Polymyxin B; D002118:Calcium; D012293:Rifampin