Lactoferrin and transferrin damage of the Gram-negative outer membrane is modulated by Ca2+ and Mg2+ Ellison, Richard T. and LaForce, F. Marc and Giehl, Theodore J. and Boose, Dorothy S. and Dunn, Bruce E.,, 136, 1437-1446 (1990), doi = https://doi.org/10.1099/00221287-136-7-1437, publicationName = Microbiology Society, issn = 1350-0872, abstract= 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+., language=, type=