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In vitro and in vivo (LD50) effects of human lactoferrin on bacteria
Abstract:
The in vitro and in vivo effects of human lactoferrin (LF), apoLF, iron saturated LF and of different iron containing compounds (ferric chloride, ferric sodium citrate) were studied on Escherichia coli, Salmonella typhi-murium and Pseudomonas aeruginosa reference and wild-type strains with well-defined virulence markers (i.e. enterochelin, aerobactin production). LF exert in vitro antibacterial effect, and iron-free Vogel-Bonner medium proved to be suitable for its determination. The effect of intraperitoneally administered LF could not be evaluated because of its aspecificity, as any treatment (e.g. saline, Ringer solution) before bacterial challenge activated macrophages. In contrast to the in vitro results, intramuscular challenge failed to inhibit bacterial growth in vivo, as siderophores produced by bacteria were able to acquire lactoferrin-bound iron. LF treatment, like iron addition, enhanced the virulence of bacteria in mice, whereas apoLF - using iron present in the body fluids - turned to LF being unable to acquire siderophore-bound iron from bacteria. These findings do not support the literary view that LF would be useful as an antimicrobial drug.
Insights
Human lactoferrin (LF) shows in vitro antibacterial effects, but in vivo studies reveal it may enhance bacterial virulence. These findings challenge the notion of LF as an effective antimicrobial drug.
Area of Science:
- Microbiology
- Immunology
- Biochemistry
Background:
- Human lactoferrin (LF) is known for its potential antimicrobial properties.
- Iron metabolism plays a crucial role in bacterial virulence and host defense.
Purpose of the Study:
- To investigate the in vitro and in vivo effects of human lactoferrin (LF) and its iron-bound forms on pathogenic bacteria.
- To evaluate the efficacy of LF as an antimicrobial agent against Escherichia coli, Salmonella typhi-murium, and Pseudomonas aeruginosa.
Main Methods:
- In vitro antibacterial assays using various bacterial strains and iron compounds.
- In vivo studies involving intraperitoneal and intramuscular administration of LF in mice challenged with bacteria.
- Assessment of bacterial virulence markers and macrophage activation.
Main Results:
- LF demonstrated in vitro antibacterial activity, particularly in iron-free media.
- In vivo administration of LF did not inhibit bacterial growth and, along with iron supplementation, enhanced bacterial virulence in mice.
- Apo-lactoferrin (apoLF) utilized host iron, becoming effective against bacteria, unlike LF which could not sequester siderophore-bound iron.
Conclusions:
- The in vitro antibacterial effects of LF do not translate to in vivo efficacy.
- LF, especially when bound to iron, may promote bacterial virulence by providing iron.
- The findings do not support the use of LF as an antimicrobial drug, suggesting a complex role in host-pathogen interactions.