Bactericidal Activity of Human Lactoferrin: Differentiation from the Stasis of Iron Deprivation (original) (raw)
Related papers
2001
The in vitro antistaphylococcal activity of lactoferrin and the antibiotic resistance of clinical Staphylococcus aureus isolates obtained from three different sites of infection were examined. Antibiotic, but not lactoferrin resistance correlated with selective antibiotic pressure, and nosocomial and most community isolates were antibiotic resistant, whereas only a third of each group was resistant to lactoferrin. The antimicrobial activity of lactoferrin, both in defined medium and in normal human plasma serum, was dependent upon its ferrochelating properties. Therapeutic approaches based on the use of ferrochelating agents such as lactoferrin combined with antimicrobial drugs may help to counteract the reduced efficacy of current antibiotics. ß
Bactericidal activity of human lactoferrin: sensitivity of a variety of microorganisms
Infection and Immunity, 1980
Lactoferrin is an iron-binding protein that has been detected in secretions that bathe human mucosal tissues. Previous studies have shown that, when this protein is in the iron-free state, it is capable of a direct bactericidal effect on Streptococcus mutans and Vibrio cholerae. The present study demonstrates variable susceptibilities for a variety of different microorganisms. The list of susceptible organisms includes gram-positive and gram-negative microbes, rods and cocci, facultative anaerobes, and aerotolerant anaerobes. Similar morphological and physiological types are represented among the lalctoferrin-resistant bacteria. S. mutans was more resistant to lactoferrin when grown on a sucrose-contaning medium than when it was grown on brain heart infusion broth without added scurose. When a lactoferrin-sensitive, avirulent strain of Streptococcus pneumoniae was passed through mice, the resultant virulent culture became lactoferrin resistant. Since organisms of the same species an...
Characterization of Lactoferrin Interaction with Streptococcus mutans
Journal of Dental Research, 1987
Lactoferrin (LF) is an iron-binding glycoprotein common to exocrine secretions and the specific granules of neutrophils. Each molecule is capable of high-affinity coordinate-binding of two ferric ions with two bicarbonate or carbonic anions. The initial aspect of the present study was directed at determining the nature of anion involvement in LF bactericidal activity. It was found that selective anions were capable of inhibiting the expression of bactericidal activity by LF on S. mutans 10449. The ability to block LF expression was directly related to the capacity of the anion to serve as a coordinate ion in iron-binding by the transferrin molecules. These data support the hypothesis that the
Interaction of lactoferrin with Escherichia coli cells and correlation with antibacterial activity
Medical Microbiology and Immunology, 1990
It has been established that the antimicrobial activity of lactoferrin towards Escherichia coli is enhanced by a direct contact between the protein and the microbial cell and that, in the case of E. coli K-12 strains, an antibacterial activity of lactoferrin unrelated to iron withdrawal is present. Evidence is now reported that lactoferrin binds to surface structures expressed in E. coli K-12 strains grown in either an “excess” or “stress” of iron. Under the experimental conditions used, lactoferrin binding both in the apo and in the iron-saturated form yields a maximum of 1.6 × 105 bound molecules/E. coli K-12 cell; the amount of lactoferrin bound does not depend on the expression of the iron-regulated outer membrane proteins. In contrast, lactoferrin does not bind to E. coli clinical isolates. Apo-lactoferrin (at 500 μ/ml in a chemically defined medium) inhibits the growth of E. coli K-12 strains but not of clinical isolates. These findings suggest that the antibacterial activity of the protein could be associated to its binding to the cell surface.
Both lactoferrin and iron influence aggregation and biofilm formation in Streptococcus mutans
BioMetals, 2000
Streptococcus mutans, a Gram-positive immobile bacterium, is an oral pathogen considered to be the principal etiologic agent of dental caries. Although some researches suggest that trace metals, including iron, can be associated with dental caries, the function of salivary iron and lactoferrin in the human oral cavity remains unclear. The data reported in this study indicates that iron-deprived saliva (Fe 3+ < 0.1 µM) increases S. mutans aggregation and biofilm formation in the fluid and adherent phases as compared with saliva (Fe 3+ from 0.1 to 1 µM), while iron-loaded saliva (Fe 3+ > 1 µM) inhibits both phenomena. Our findings are consistent with the hypothesis that S. mutans aggregation and biofilm formation are negatively iron-modulated as confirmed by the different effect of bovine lactoferrin (bLf), added to saliva at physiological concentration (20 µg/ml) in the apo-or iron-saturated form. Even if saliva itself induces bacterial aggregation, iron binding capability of apo-bLf is responsible for the noticeable increase of bacterial aggregation and biofilm development in the fluid and adherent phases. On the contrary, iron-saturated bLf decreases aggregation and biofilm development by supplying iron to S. mutans. Therefore, the iron-withholding capability of apo-Lf or native Lf is an important signal to which S. mutans counteracts by leaving the planktonic state and entering into a new lifestyle, biofilm, to colonize and persist in the human oral cavity. In addition, another function of bLf, unrelated to its iron binding capability, is responsible for the inhibition of the adhesion of S. mutans free, aggregated or biofilm on abiotic surfaces. Both these activities of lactoferrin, related and unrelated to the iron binding capability, could have a key role in protecting the human oral cavity from S. mutans pathogenicity.
Antibacterial activity of Lactoferrin and Lactoferricin against oral Streptococci
Romanian …, 2010
Lactoferrin (Lf) is an iron-binding glycoprotein which exhibits antibacterial activity against a broad range of Gram-negative and Gram-positive bacteria. The mechanisms of this property are complex and involve iron sequestration as well as direct interaction with bacteria. Lactoferricin (LFcin), a Lf-derived peptide released by pepsin digestion of lactoferrin, is a more potent antibacterial compound than the native protein. In this study the antibacterial capacity of iron-free Lf, either human or bovine, and bovine Lfcin against the growth of some oral streptococci was investigated. Both human and bovine Lf, and bovine Lfcin were found to exert bacteriostatic effects which were dependent on their concentration and the streptococcal species tested. Even within species, strains exhibited different susceptibilities to the action of Lfs and Lfcin. The most sensitive streptococcal species were S. parasanguinis, S. gordoni and S. plurianimalium. Bovine Lfcin was also bactericidal against S. plurianimalium strain 5.1 at 9mg/ml. These findings are encouraging for the use of Lf/Lfcin as compounds with antimicrobial activity against oral streptococci.
A multifunctional bioactive protein: Lactoferrin
Lactoferrin which is also known by the name of lactotransferrin (LTF), is a multifunctional iron-binding glycoprotein of the transferrin family and is found in almost all human mucosal secretions as well as in the specific granules of polymorphonuclear leukocytes in blood. A variety of functions have been found to associated with this protein along with its contribution to antimicrobial host defense mechanism. Moreover, it has been shown to have direct effects on some of the pathogenic microorganisms through bacteriostatic and microbial iron uptake induction. Several studies have shown that the protein synergistically interacts with immunoglobins, complement, and neutrophil cationic proteins which act against Gram-negative bacteria. Further, both the whole protein and a cationic N-terminus peptide fragment directly damage the outer membrane of Gram-negative bacteria suggesting a mechanism for its supplemental antimicrobial effects. It has appeared logical that antimicrobial activity of the protein arises from sequestration of environmental iron thereby causing nutritional deprivation of iron in susceptible organisms. Lactoferrin has diverse role where it can be used as an immunotherapeutic and can also play a role in immunodiagnostics. Still its overall physiologic role remains yet to be defined clearly inside the living system.
Antibacterial Activity of Lactoferrin: A Review
Milk is a highest quality source of well balanced nutrients and also displays a range of biological activities that affects digestion, metabolic responses to absorbed nutrients, growth & development of specific organs, and resistance to disease. Bioactive proteins such as lactoferrin (Lf) have been isolated over decades ago and showed their importance in stimulating immune system in the infants through breast milk in addition to immunoglobulin present in the milk. In addition to immune system stimulation, Lf also has antibacterial activity and antioxidant activity in infant and adult of human as well as animal health. In this review paper, antibacterial properties of lactoferrin have been discussed along with its future perspectives.
Lactoferrin—a multifunctional protein with antimicrobial properties
Molecular Immunology, 2003
Lactoferrin is a member of the transferrin family of iron-binding proteins. Numerous functions have been reported and continue to be reported for the protein, some of which are related to its iron-binding properties. Its extensive antimicrobial activities were originally attributed to its ability to sequester essential iron, however, it is now established that it possesses bactericidal activities as a result of a direct interaction between the protein or lactoferrin-derived peptides. This article reviews the antimicrobial activities of lactoferrin and discusses the potential mode of action of lactoferrin-derived cationic peptides against Gram-negative bacteria in the light of recent studies.