Lactoferrin (LF), a glycoprotein of exocrine secretions and specific granules of the polymorphonuclear leukocyte, is capable of high affinity coordinate binding of ferric ions and either CO3- or HCO3-. A variety of properties have been described for this molecule that may contribute to its biological functions. LF is capable of withholding iron from many bacteria; however, this does not appear to be its effect on Streptococcus mutans as it is capable of using LF associated iron for growth. LF is also capable of direct bactericidal effects on many microorganisms including the oral streptococci. The mechanisms involved in the cidal event have not been elucidated, though it is clearly independent of iron deprivation. The overall objectives of these studies are to define the mechanism(s) involved in LF killing and determine the biological relevance of this activity. We propose to further define those variables that modify LF-mediated effects on selected bacteria. The possibility that OH is involved in LF-mediated killing will be approached by investigating the effects of anaerobiosis, radical scavengers and H2O2-handling enzymes of LF activity. We intend to refine the observations of temperature and pH dependence of LF killing and relate these data to effects on cell functions. A medium that both supports the growth of E. coli and allows the expression of the bactericidal activity of LF will be used to study the kinetics of LF effects on metabolic events and the effects of various antibiotics on LF expression. We propose to develop a medium that allows similar studies with S. mutans. Our data suggest the hypothesis that the target site on the bacterial cell surface is anionic and that LF requires iron for the coordinate binding of this target. We propose to identifying he nature of those components capable of competitively inhibiting LF binding and LF killing. Activity of chemically modified LF and defined molecular subunits will be related to suspected prosthetic groups of the LF molecule. Depending on the species of the target bacterium, preliminary data suggest that SIgA may either block or enhance expression of LF killing. Studies are proposed to clarify the specificity of these effects, to determine the nature of these interactions and to relate the specificities with the suspected LF target sites. We propose to chemically and bilogically compare LF isolated from saliva dn PMNs with that from colostrum to determine if extrapolations of functions of molecules from one source to another are valid. We further propose to study the effects of LF on potential periodontopathic bacteria.
Showing the most recent 10 out of 12 publications
