Bactericidal Activity of Human Lactoferrin: Differentiation from the Stasis of Iron Deprivation

Abstract

Previous studies have demonstrated a direct iron-irreversible inhibition of a variety of microorganisms by human apolactoferrin. The present study compared the bactericidal effects of lactoferrin on Streptococcus mutans with the bacteriostatic effects of iron deprivation. Growth (as determined by change in optical density) and macromolecular synthesis, as determined by incorporation of 14Clabeled uracil, thymidine, and lysine, were inhibited by incubation of washed exponential-phase S. mutans NCTC 10449 with purified human apolactoferrin. Similarly, apolactoferrin inhibited glucose uptake and metabolism. Iron-saturated lactoferrin had no effect on bacterial growth or metabolism and was capable of serving as a source of iron in iron-depleted medium. S. mutans failed to grow, and there was no indication of macromolecular synthesis in iron-depleted partially defined medium; however, glucose metabolism continued, though at a reduced rate, and viability was retained for 72 h. There was no detectable metabolism of glucose by cells maintained for 18 h in iron-free medium. Metabolism was restored by transfer of iron-depleted S. mutans to iron-complete medium. This was in contrast to the irreversible inhibition by lactoferrin after 1 h of incubation. Inhibition could not be reversed by removal of cell surface-associated lactoferrin as detected by rhodamine isothiocyanate-labeled antilactoferrin. This inhibition of metabolism and rapid loss in viability observed with lactoferrin treatment suggest that lactoferrin has a direct bactericidal effect on S. mutans that cannot be attributed to simple iron deprivation.

Influence of aging on candidal growth and adhesion regulatory agents in saliva

“…Of these proteins, Lf and Tf bind iron and inhibit iron utilization by Candida (35,36). However, it has recently been reported that the inhibition of candidal growth by Lf depends not only on the ironbinding capacity but also on its direct inhibitory activity (37,38). We ascertained that candidal growth inhibition by saliva was closely correlated with the Lf level (16).…”

Distribution of lactoferrin in the normal and inflamed human prostate: An immunohistochemical study

“…This protein is ubiquitous in epithelial secretions of many organs [2,3], and there is evidence that it plays an important role as an antibacterial agent due to its ability to bind iron, a necessary factor for bacterial growth. Lactofemn may also be able to modulate immunological responses [4,5].…”

Lactoferrin: Similarity to Diamine Oxidase and Purification by Aminohexyl Affinity Chromatography

“…DAO generates hydrogen peroxide and cytotoxic aminoaldehydes in the oxidation of polyamines (Bachrach, 1985) and may therefore contribute to the antimicrobial activity both by supplying hydrogen peroxide for myeloperoxidase and by the aminoaldehydes generated. Lactoferrin may influence the Fenton or the Haber-Weiss reaction (Ambruso and Johnston, 1981;Aruoma and Halliwell, 1987) and may also have antimicrobial activity by itself or by its iron-binding capacity (Arnold et al, 1977(Arnold et al, , 1982Dionysius et al, 1993).…”