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Lactoferrin
Frederic R. Sallmann
Rersearch Experience: Antibacterial activity of Lactoferrin
The biological roles of Lf include antibacterial activities through mechanisms not yet clearly elucidated. However, it is known that the binding of Lf to the outer membrane of
Gram-negative bacteria is a prerequisite to exert its bactericidal activity. It was proposed that porins in addition to lipopolysaccharides are responsible for this binding. Therefore, we studied the interactions of human lactoferrin (hLf) with the three major porins of E. coli OmpC, OmpF and PhoE. We investigated whether hLf specifically binds to porins and how it does. Binding experiments were performed on both purified porins and porin-deficient E. coli K12 isogenic mutants. We determined that lactoferrinbinds to the purified native OmpC or PhoE trimer with a high affinity, but not to OmpF. Furthermore, preferential binding of lactoferrin was observed on strains that express either OmpC or PhoE. It was also demonstrated that residues 1-5, 28-34, and 39-42 of lactoferrin interact with porins. The relationships between binding and antibacterial activity of the protein were studied using E.coli mutants and planar lipid bilayers. Electrophysiological studies revealed that lactoferrin can act as a blocking agent for OmpC but not for PhoE or OmpF. However, a total inhibition of the growth was only observed for the PhoE-expressing strain. These data support the proposal that the antibacterial activity of lactoferrin may depend, at least in part, on its ability to bind to porins, thus modifying the stability and/or the permeability of the bacterial outermembrane. This work was published in the Journal of Biological Chemistry.
 These findings might be useful for development of a new class of antibiotic. Peptides corresponding to the lactoferrin-porin interaction domain might indeed have the capacity to kill pathogen bacteria. Beside, lactoferrin is now used as additive in toothpaste to fight against mouth bacteria responsible for cavities.
Links:

Dominique Legrand (under construction)
Publications:

F.R. Sallmann, S. Baveye-Descamps, F. Pattus, V. Salmon, N. Branza, G. Spik, D. Legrand. 1999. OmpC and PhoE porins of Escherichia coli as specific cell-surface targets of human lactoferrin. Binding characteristics and biological effects. J. Biol. Chem. 274(23):16107-14

 F.R. Sallmann, S. Baveye-Descamps, F. Pattus, V. Salmon, N. Branza, G. Spik, D. Legrand. 1999. Binding of human lactoferrin to Escherichia coli porins: a biochemical Study. in Lactoferrin, Structure, Function and Applications (K. Shimazaki, ed) Elsevier, Amsterdam (in press)

F.R. Sallmann, S. Baveye-Descamps, F. Pattus, V. Salmon, N. Branza, G. Spik, D. Legrand. May 18-22, 1999. Binding of human lactoferrin to Escherichia coli porins: a biochemical study. Fourth International Conference on Lactoferrin, Sapporo (Japon)

F.R. Sallmann, S. Baveye-Descamps, F. Pattus, V. Salmon, N. Branza, G. Spik, D. Legrand. 27-29 April 1998. Porins OmpC and PhoE of E. coli as specific targets of human lactoferrin, binding characteristics and biological effects " 5ème Congrès de la Société Française de Microbiologie. Lille - Grand Palais (France).

 

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