Lactoferrin and Its Derived Peptides: An Alternative for Combating Virulence Mechanisms Developed by Pathogens
Abstract
:1. Introduction
2. Lactoferrin: General Features
2.1. Human and Bovine Lactoferrin
2.2. Lactoferrin-Derived Natural Peptides (Lactoferricins)
2.3. Lactoferrin-Derived Synthetic Peptides
3. Antibacterial Activity of Lactoferrin
3.1. Lactoferrin as a Bacteriostatic and Bactericidal Factor
3.2. Effect of Lactoferrin and Lactoferricins on the Bacterial Membrane Structure and Function
3.3. Effect of Lactoferrin and Lactoferricins on Microbial Biofilms
3.4. Effect of Lactoferrin and Lactoferricins on Bacterial Proteolytic and Oxidative Enzymes
3.5. Effect of Lactoferrin and Lactoferricins on Bacterial Toxins
3.6. Effect of Lf on Bacterial Adherence to Host Surfaces
4. Antiparasitic Activity of Lactoferrin
4.1. Main Treatments against Parasitic Diseases
4.2. Effect of Lactoferrin and Lactoferricins on Parasite Growth/Viability
4.3. Effect of Lactoferrin and Lactoferricins on The Parasite Structure
4.4. Effect of Lactoferrin and Lactoferricins on Parasite Virulence
5. Antifungal Activity of Lactoferrin
5.1. Fungal Diseases
5.2. Iron Requirement in Fungi and The Iron Chelation Effect of Lactoferrin
5.3. Direct or Indirect Interaction of Lactoferrin and Lactoferricins with the Fungal Cell Surface
5.4. Effect of Lactoferrin on Mitochondrial and Caspase-Dependent Regulated Cell Death
5.5. Fungal H+ ATPase (P3A-type) Is a Target of Lactoferrin, which Induces an Apoptosis-Like Process
5.6. Fungal Alteration of Responses to Stress due to Lactoferrin
5.7. Other Unspecified Antifungal Activities of Lactoferrin
6. Antiviral Effect of Lactoferrin
6.1. Effect of Lactoferrin and Lactoferricins on the Viral Process of Infection
6.2. Binding of Lactoferrin to Target Cell Receptors
6.3. Binding of Lf to Viral Particles
7. Conclusion and Perspectives
Funding
Conflicts of Interest
References
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Pathogens (Bacteria) | Source and Type of Lf/Iron-Saturated Condition | Effect on Viability/Growth/ Concentration | Other Effects In Vitro/Concentration | Ref. | |
---|---|---|---|---|---|
Actinobacillus pleuropneumoniae | apo-bLf (N) | - | Inhibited adhesion on porcine buccal epithelial cells: 0.8 µM | [123] | |
A. actinomycetemcomitans | hLf, bLf (N) | - | Inhibited adhesion on fibroblasts: 0.5–2500 pg/mL | [122] | |
Prevotella intermedia | |||||
Escherichia coli | hLf (N) | - | Inhibited adhesion to HeLa cells: 20 and 30 mM | [121] | |
bLf (N), bLfcin (N) | Bactericidal activity bLf: 13 µg/mL | Released LPS: bLf: 2 mg/mL, Lfcin: 100 µg/mL. Appearance of membrane “blisters” bLfcin: 100 µg/mL | [86] | ||
Lfcin (N), Lframpin (S) | Bactericidal activity: Lframpin and Lfcin: 20 µM | Membrane damage and release of vesicle-like structures: Lframpin and Lfcin: 20 µM | [87] | ||
LfcinB (N) | Bactericidal activity: 3 µM | Membrane permeabilization: 3 µM | [90] | ||
apo-Lfb (N), Lfcin (N), Lfampin (S), Lfchimera (S) | Bactericidal activity: bLf, Lfcin, Lfampin: 20 and 40 µM, Lfchimera: 1 µM bLf and peptides + LPS (10–100-fold): counteracts the inhibitory effect of Lf. Synergistic effect with antibiotics: Lfampin, Lfcin 10 µM + ampicillin | Lfchimera induced membrane permeabilization: 1 µM | [81] | ||
Staphylococcus aureus | |||||
E. coli | Lf (N) | - | Antibiofilm activity: 40 µg/mL | [102] | |
Klebsiella pneumoniae | |||||
Mannheimia haemolytica | apo-bLf (N) holo-bLf (N) | Bactericidal activity apo-Lfb: 12 µM | Membrane permeabilization and damage, increased the release of OMVS Apo-Lfb: 2–10 µM: Increased secretion of Lkt 2–10 µM | [89] | |
Pseudomonas aeruginosa | apo-bLf (N), Lfcin (N), Lfampin (S), Lfchimera (S) | Bactericidal activity: Lfb: 9.4 µM, Lfcin: 2.9 µM, Lfampin: 5.8 µM, Lfcin + Lfampin: 1.4 µM, Lfchimera: 0.9 µM | Inhibited pyocyanin, elastase and biofilm production: 1, 5, 25 µM | [68] | |
Synthetic cationic peptides and lipopeptides from hLf | Bactericidal activity: 8–128 mg/mL depending on the peptide | Antibiofilm activity 10-fold major MIC | [106] | ||
apo-bLf (N) | Bactericidal activity: 2% | Antibiofilm activity: 2% | [101] | ||
Pseudomonas fluorescens | bLf hydrolysate (N) | - | Antibiofilm activity: 3 mg/mL | [112] | |
Prevotella intermedia | hLf (N), apo-bLf (N), holo-bLf (N), LfcinB (N) | Bactericidal activity: hLf, apo-bLf, and holo-bLf: 0.13 to 8 mg/mL, Lfcin B at 0.006 to 0.4 mg/mL Synergistic effect with antibiotics: 0.1 or 10 g/mL of ABPC, CPFX, CAM, or MINO + 0.5 mg/mL native bLf or apo-bLf | Antibiofilm activity: P. gingivalis hLf, apo-, holo-bLf: 0.008 mg/mL LfcinB: 0.4 mg/mL P. intermedia: apo-, holo-bLf: >0.31 mg/mL, hLf: >0.13 mg/mL, LfcinB: 0.4 mg/mL | [104] | |
Porphyromonas gingivalis | |||||
apo-bLf (N), holo-bLf (N) | - | Anti-proteinase activity: 5 mg/mL Inhibited biofilm formation: 0.065 mg/mL | [108] | ||
Streptococcus mutants | apo-bLf (N), holo-bLf (N) | Bactericidal activity apo- and holo-Lfb: 20 µg/mL | Decreased aggregation and biofilm development: 20 µg/mL | [109] | |
Streptococcus pneumoniae | apo-bLf (N), Lfcin (N) Lfampin (S), Lfchimera (S) | - | Diminished adhesion on laryngeal, lung and nasopharyngeal human cells: 40 µM bLf and 10 µM peptides Eradicated pneumococcal preformed biofilms: 40 and 80 µM bLf eDNAase activity: 40 µM bLf | [103] | |
apo-bLf (N), Lfcin (N) Lfampin (S), Lfchimera (S) | apo-Lfb: 40 µM Lfcin, Lfampin, Lfchimera: 10 µM | Ultrastructural damage: 40 µM for all peptides | [88] | ||
STEC (Stx-producing Escherichia coli) | apo-bLf (N) | - | Decreased Stx2 secretion: 0.1, 1, 10 mg/mL Diminished verotoxicity: 0.1 or 1 mg/mL Protease activity: 1000, 100, 10, 1 mg/mL | [119] | |
Vibrio cholerae O1 and non-O1 strains | bLf (N), Lfcin (N), Lfampin (S), Lfchimera (S) | Bactericidal activity: bLf: 40 mM, bLFcin: 20 μM, Lfampin: 20 μM, Lfchimera: 5 μM Synergistic effect with antibiotics: 1 μM Lfchimera + 2.5 µg/mL chloramphenicol 10 μM LF + 2.5 µg/mL chloramphenicol | Membrane permeabilization, vesicularization and membrane damage Lfchimera: 5 μM; bLf, Lfcin and Lfampin: 20 μM | [70] | |
Vibrio parahaemolyticus | Lfchimera (S) | Lfchimera: 40 µM antibiotics 5μM Lfchimera + 5 µg/mL ampicillin, gentamicin, kanamycin | Membrane permeabilization, vesicularization and membrane damage Lfchimera: 40 μM | [91] | |
Yersinia enterocolitica/pseudotuberculosis | bLfcin (S) | Bactericidal activity: 4 mg/mL | Enhanced adhesion on Hep-2 cells Bacterial internalization is inhibited | [124] |
Pathogen (Parasite) | Source and Type of Lf/Iron-Saturated Condition | Effect on Viability/Growth Concentration | Other Effects in Vitro Concentration | Effects In Vivo Dose | Ref. |
---|---|---|---|---|---|
Acanthamoeba spp. | apo-bLf (N) | Decreased viability Growth inhibition 10 µM | Decreased encystment ratio. The cyst could not retransform to trophozoite. 10 µM | - | [142] |
Cryptosporidium parvum | bLf (N) | Decreased viability 1–10 mg/mL | Decreased infectivity to HCT-8 cells 10 mg/mL | - | [146] |
E. histolytica | apo-hLf(N), apo-bLf (N), Lfcin (N) | Decreased viability, 12.5–100 µM, 64.7–647 µM | Synergism with metronidazole 31.25 µM 323–453 µM | - | [60] |
Lfampin (S) | Decreased viability 250–1000 µM | Killed trophozoites by lysis, 250 µM | Resolved amoebic intracecal infection in mice: 10 mg/kg daily for 4 days Lfcin17–30, LfcinB: absence of amoebic trophozoites in the lumen of 75% of the animals or a decrease in parasitic load | [145] | |
apo-bLf (N) | - | - | Resolved intracecal infection in C3H/HeJ mice: 63.14% totally and 36.86% partially. Increased IgA, Induced Th2 response, 20 mg/kg daily for 7 days | [176] | |
apo-bLf (N) | - | - | Resolved hepatic amoebiasis in hamster (decrease of lesions) Proteins, enzymes and hepatic cells returned to normal parameters: 2.5 mg/100 g mass daily for 8 days | [177] | |
Human milk (N), apo-hLf (N), apo-bLf (N) | Decreased viability 5–20%, 1 mg/mL | Synergism with lysozyme and IgA: 1 mg/mL. Synergism with porcine milk: 1 mg/mL | - | [141] | |
Lfcin17-30 (N), Lfampin265-284 (S), Lfchimera (S) | Decreased viability, 25–100 µM | - | - | [71] | |
E. stiedai | Lfcin (N) | - | Decreased infectivity to rabbit hepatobiliary cells, 100–1000 µg/mL | Decreased number of oocysts in the feces of rabbits inoculated with treated sporozoites. Fewer abscesses and bile ducts were not swollen: 1000 µg/mL | [178] |
Giardia intestinalis | bLf (N), Lfcin 17–30 (N), Lfampin 265–284 (S), Lfchimera (S) | Decreased viability Growth inhibition, 40 µM | Synergism with metronidazole, albendazole Peptides 40 µM. Morphological alterations: Electron-dense material in cytoplasm, reorganization of flagellum, displacement of adherent disk, membrane disruption, shrunken and distorted peripheral vacuoles. Apoptosis: 40 µM | - | [144] |
bLf (N), Lfcin (N) | Growth inhibition, 12.5–50 µM, 1.3–3.9 µM | Morphological alterations: Vesiculation of ER, enlargement of nuclear envelope, delocalization and electron-dense PVs, changes in the cytoskeleton, invaginations and protrusions of plasma membrane, induced differentiation to cyst. Production of futile cysts: 12.5 µM, 2.6 µM | - | [143] | |
Haemonchus contortus | Camel’s milk (N) | - | Inhibited egg hatching Inhibition of motility 5–100 mg/mL | - | [179] |
Plasmodium berghei | apo-buLf (N) | - | - | Decreased infectivity to RBCs Reduced parasite load in mice Histopathology: Spleen: Decreased pigmentation. Liver: Decreased inflammation. Less accumulation of histiocytes and lymphocytes. Increased ROS and NO production. Expression of various miRNA genes required in Fe regulation. Upregulation of innate immune cytokines Increased Th1 response Increased survival of infected mice: 12 g bLf (Fe-bLf)/kg of diet | [180] |
Plasmodium falciparum | apo-hLf (N) | Growth inhibition (RBC preincubation) 30 µM | Parasites could not develop from ring stages to trophozoites, 30 µM | - | [166] |
hLf (N) (isolated fraction) | Growth inhibition 2 mg/mlL | - | - | [181] | |
Toxoplasma gondii | apo-bLf (N) holo-bLf (N) | Lf suppressed the intracellular growth of parasites, 100–1000 µg/mL | - | - | [182] |
Lfcin (N) | - | Decreased infectivity to MEC 100–1000 µg/mL | Increased survival of mice infected with treated sporozoites. Mice did not show clinical signs of infection: 1000 µg/mL | [178] | |
holo-hLf (N) | Significantly inhibited the intracellular growth, 0.1–100 µg/mL | - | - | [149] | |
native-bLf (N) apo-bLf (N) | - | Decreased infectivity to macrophages (mice J7741). Decreased number of tachyzoites per macrophage. Increased production of NO in macrophages, 20 µg/mL | Histopathology: Liver: No signs of pathology or infection Decreased parasite load Spleen: Decreased parasite load Increased ROS/NO production Increased cytokine production Elevated levels of different iron regulators Increased survival of infected mice: 12 g/kg of diet | [183] | |
Trypanosoma cruzi | hLf (N) | - | Monocyte and macrophage stimulation Increased phagocytic capacity Stimulated intracellular killing capacity of HBM or MPM | - | [152] |
apo-hLf (N) | - | Macrophages had greater capacity to internalize and kill trypomastigotes: 10 µg/mL | - | [184] |
Pathogen (Fungal) | Source and Type of Lf/iron-Saturated Condition | Concentration | Effect on Viability | Ref. |
---|---|---|---|---|
Absidia corymbifera | bLfcin (N) | In Vitro MIC: 40->80 μg/mL | Interaction with cell surface/alteration of cell membrane | [208] |
Aspergillus clavatus | bLfcin (N) | In Vitro MIC: >80 μg/mL | Interaction with cell surface/alteration of cell membrane | [208] |
Aspergillus fumigatus | apo-hLf (N), apo-hLf(N) + amphotericin B | In Vitro IC50: ~10 (conidia)-80 μg/mL (hyphae) IC50: 10 nM | Iron deprivation | [198,199] |
bLfcin (N) | In Vitro MIC: 45–80 μg/mL | Interaction with cell surface/alteration of cell membrane | [207,208] | |
Aspergillus flavus | bLfcin (N) | In Vitro MIC: >80 μg/mL | Interaction with cell surface/alteration of cell membrane | [208] |
Aspergillus niger | bLfcin (N) | In Vitro MIC: 30–80 μg/mL | Interaction with cell surface/alteration of cell membrane | [207,208] |
Aspergillus versicolor | bLfcin (N) | In Vitro MIC: 10 μg/mL | Interaction with cell surface/alteration of cell membrane | [208] |
Candida albicans | apo-hLf (N), ovotransferrin (N) | In Vitro 5–200 μg/Ml 1 mg/mL 5 μM | Iron deprivation Interaction with cell surface/alteration of cell membrane H+ ATPase (P3A-type) | [195,201,202,203,205,218,220] |
apo-bLf (N) | In Vitro 20 μg/mL | Interaction with cell surface/alteration of cell membrane | [204] | |
bLfcin (N) | In Vitro 10–60 μg/mL bLfcin (100 µg/mL) + fluconazole or itraconazole (25 µg/mL) | Interaction with the cell surface | [206,207,208,212] | |
bLF (N), Lfampin (S), bLfcin (N) | In Vitro 20 μM | Interaction with cell surface/alteration of cell membrane | [87] | |
Lfpep (S), kaliocin-1 (S) | In Vitro MIC: 18.7 μM MIC: 150 μM | Interaction with cell surface/alteration of cell membrane | [209] | |
apo-hLf (N)+ nystatin apo-hLf (N) + amphotericin B apo-hLf (N) + clotrimazole apo-hLf(N) + miconazole apo-hLf (N) + 5-fluorocytosine apo-hLf (N) + tunicamycin | In Vitro MIC: apo-hLf (20 μg/mL) + nystatin (2.0μg/mL) apo-hLf (20 μg/mL) + amphotericin B (0.4 μg/mL) apo-hLf (20 μg/mL) + clotrimazole (10 μg/mL) apo-hLf (20 μg/mL) + miconazole (4 μg/mL) apo-hLf (20 μg/mL) + 5-fluorocytosine (4 μg/mL) apo-hLf (20 μg/mL) + tunicamycin (40 μg/mL) | Interaction with cell surface/alteration of cell membrane | [210] | |
apo-bLf (N) + amphotericin B apo-bLf (N) + fluconazole apo-bLf (N) + murine neutrophils | In Vitro apo-bLf (0.5–98 mg/mL) + amphotericin B (0.06–0.2 μg/mL) apo-bLf (0.5–98 mg/mL) + fluconazole (10 μg/mL) apo-bLf (110 μg/mL) + murine neutrophils (40 μg/mL) | Iron deprivation Interaction with cell surface/alteration of cell membrane | [196,213] | |
bLfcin (N) + clotrimazole bLfcin (N) + ketoconazole bLfcin (N) + fluconazole bLfcin (N) + itraconazole | In Vitro bLf (100 μg/mL) + clotrimazole (12.5 ng/mL) bLf (100 μg/mL) + ketoconazole (3.1 ng/mL) bLf (100 μg/mL) + fluconazole (1000 ng/mL) bLf (100 μg/mL) + itraconazole (12.5 ng/mL) bLfcin (3.1 mg/mL) + clotrimazole (12.5 ng/mL) bLfcin (3.1 mg/mL) + ketoconazole (12.5 ng/mL) bLfcin (3.1 mg/mLl) + fluconazole (4000 ng/mL) bLfcin (3.1 mg/mL) +itraconazole (12.5 ng/mL) | Interaction with cell surface/alteration of cell membrane Synergistic activity with azoles | [211] | |
Candida glabrata | apo-bLf (N) | In Vitro 20 μg/mL | Interaction with cell surface/alteration of cell membrane | [204] |
bLfcin (N) | In Vitro MIC: 80->80 μg/mL | Interaction with cell surface/alteration of cell membrane | [208] | |
Lfpep (S), kaliocin-1(S) | In Vitro MIC: 9.3 μM MIC: 150 μM | Interaction with cell surface/alteration of cell membrane | [209] | |
apo-bLf (N)+ amphotericin B apo-bLf (N)+ fluconazole | In Vitro MIC: apo-bLf (<5–57 mg/mL) + amphotericin B (0.1-0.4 μg/mL) apo-bLf (<5–57 mg/mL) + fluconazole (24–156 μg/mL) | Interaction with cell surface/alteration of cell membrane | [213] | |
Candida guilliermondii | apo-bLf (N) | In Vitro 20 μg/mL | Interaction with cell surface/alteration of cell membrane | [204] |
bLfcin (N) | In Vitro MIC: 5–40 μg/mL | Interaction with cell surface/alteration of cell membrane | [208] | |
Lfpep (S), kaliocin-1 (S) | In Vitro MIC: 9.3 μM MIC: 150 μM | Interaction with cell surface/alteration of cell membrane | [209] | |
Candida kefyr | bLfcin (N) | In Vitro MIC: 2.5–10 μg/mL | Interaction with cell surface/alteration of cell membrane | [208] |
Candida krusei | apo-hLf (N) | In Vitro 5–200 μg/mL | Interaction with cell surface/alteration of cell membrane | [202,203,204,220] |
bLfcin (N) | In Vitro MIC: 10–20 μg/mL | Interaction with cell surface/alteration of cell membrane | [208] | |
Lfpep (S), kaliocin-1 (S) | In Vitro MIC: 4.7 μM MIC: 150 μM | Interaction with cell surface/alteration of cell membrane | [209] | |
Candida parapsilosis | apo-bLf (N) | In Vitro 20 μg/mL | Interaction with cell surface/alteration of cell membrane | [204] |
bLfcin (N) | In Vitro MIC: 20–80 μg/mL | Interaction with cell surface/alteration of cell membrane | [208] | |
Lfpep (S), kaliocin-1 (S) | In Vitro MIC: 9.3 μM MIC: 150 μM | Interaction with cell surface/alteration of cell membrane | [209] | |
Candida tropicalis | apo-bLf (N) | In Vitro 20 μg/mL | Interaction with cell surface/alteration of cell membrane | [204] |
bLfcin (N) | In Vitro MIC: 0.31–1.25 μg/mL | Interaction with cell surface/alteration of cell membrane | [208] | |
Lfpep (S), kaliocin-1 (S) | In Vitro MIC: 9.3 μM MIC: 150 μM | Interaction with cell surface/alteration of cell membrane | [209] | |
Cladosporium trichoides | bLfcin (N) | In Vitro MIC: 5 μg/mL | Interaction with cell surface/alteration of cell membrane | [208] |
Cryptococcus curvatus | bLfcin (N) | In Vitro MIC: 3-9 μg/mL | Interaction with cell surface/alteration of cell membrane | [207] |
Cryptococcus gattii | apo-bLf (N) | In Vitro MIC: 64 μg/mL | Iron deprivation | [200] |
Cryptococcus neoformans | apo-bLf (N) apo-bLf (N) + amphotericin B | In Vitro MIC: 32–64 μg/mL apo-bLf (8 μg/mL) + amphotericin B (0.25 μg/mL) | Iron deprivation Altered responses to stress | [200,219] |
bLfcin (N) | In Vitro MIC: 0.63 μg/mL | Interaction with cell surface/alteration of cell membrane | [208] | |
Cryptococcus uniguttulatus | bLfcin (N) | In Vitro MIC: 3–6 μg/mL | Interaction with cell surface/alteration of cell membrane | [207] |
Epidermophyton floccosum | bLfcin (N) | In Vitro MIC: 0.31–2.5 μg/mL | Interaction with cell surface/alteration of cell membrane | [208] |
Exophiala dermatidis | bLfcin (N) | In Vitro MIC: 2.5 μg/mL | Interaction with cell surface/alteration of cell membrane | [208] |
Fonsecaea pedroi | bLfcin (N) | In Vitro MIC: 5 μg/mL | Interaction with cell surface/alteration of cell membrane | [208] |
Fusarium moniliforme | bLfcin (N) | In Vitro MIC: 2.5–5 μg/mL | Interaction with cell surface/alteration of cell membrane | [208] |
Microsporum canis | bLfcin (N) | In Vitro MIC: 40 μg/mL | Interaction with cell surface/alteration of cell membrane | [208] |
Microsporum gypseum | bLfcin (N) | In Vitro MIC: 20–40 μg/mL | Interaction with cell surface/alteration of cell membrane | [208] |
Mucor circinelloides | bLfcin (N) | In Vitro MIC: >80 μg/mL | Interaction with cell surface/alteration of cell membrane | [208] |
Mucor racemosus | bLfcin (N) | In Vitro MIC: >80 μg/mL | Interaction with cell surface/alteration of cell membrane | [208] |
Nannizzia gypsea | bLfcin (N) | In Vitro MIC: 30->60 μg/mL | Interaction with cell surface/alteration of cell membrane | [207] |
Nannizzia incurvata | bLfcin (N) | In Vitro MIC: 6–18 μg/mL | Interaction with cell surface/alteration of cell membrane | [208] |
Nannizzia otae | bLfcin (N) | In Vitro MIC: 12–60 μg/mL | Interaction with cell surface/alteration of cell membrane | [207] |
Paracoccidioides brasiliensis | bLfcin (N) | In Vitro MIC: 0.63–1.25 μg/mL | Interaction with cell surface/alteration of cell membrane | [208] |
Penicillium expansum | bLfcin (N) | In Vitro MIC: >80 μg/mL | Interaction with cell surface/alteration of cell membrane | [208] |
Penicillum notatum | bLfcin (N) | In Vitro MIC: >80 μg/mL | Interaction with cell surface/alteration of cell membrane | [208] |
Penicillium pinophilum | bLfcin (N) | In Vitro MIC: 3–45 μg/mL | Interaction with cell surface/alteration of cell membrane | [207] |
Penicillium vermiculatum | bLfcin (N) | In Vitro MIC: 6–45 μg/mL | Interaction with cell surface/alteration of cell membrane | [207] |
Phialophora verrucosa | bLfcin (N) | In Vitro MIC: 5–10 μg/mL | Interaction with cell surface/alteration of cell membrane | [208] |
Rhizopus oryzae | bLfcin (N) | In Vitro MIC: 60 ≥ 80 μg/mL | Interaction with cell surface/alteration of cell membrane | [207,208] |
Saccharomyces cerevisiae | apo-hLf (N) | In Vitro 1.56–6.25 µM | Mitochondrial and caspase-dependent regulated cell death | [216] |
apo-bLf (N) | In Vitro MIC: 16 μg/mL | Iron deprivation | [200] | |
bLfcin (N) | In Vitro MIC: 0.63 μg/mL | Interaction with cell surface/alteration of cell membrane | [208] | |
Sporothrix schenckii | bLfcin (N) | In Vitro MIC: 2.5–10 μg/mL | Interaction with cell surface/alteration of cell membrane | [208] |
Trichophyton cutaneum | bLfcin (N) | In Vitro MIC: 1.25–2.5 μg/mL | Interaction with cell surface/alteration of cell membrane | [208] |
Trichophyton mentagrophytes | bLfcin (N) | In Vitro MIC: 6 ≥ 80 µg/mL | Interaction with cell surface/alteration of cell membrane | [207,208] |
Trichophyton rubrum | bLfcin (N) | In Vitro MIC: 12 ≥ 80 µg/mL | Interaction with cell surface/alteration of cell membrane | [207,208] |
Trichphyton shoenleinii | bLfcin (N) | In Vitro MIC: >80 μg/ml | Interaction with cell surface/alteration of cell membrane | [208] |
Trichophyton spp. | hLf (N) bLf (N) bLfcin (N) | In Vitro MIC: hLf (400, 800 and 13 mg/L) bLf (50, 100 and 13 mg/L) bLfcin (3.1, 6.3, 13 mg/L) In vivo Guinea pigs Doses: 2.5 g/kg/day for 28 days | Interaction with cell surface/alteration of cell membrane | [221] |
Trichophyton tonsurans | bLfcin (N) | In Vitro MIC: 5–40 μg/mL | Interaction with cell surface/alteration of cell membrane | [208] |
Trichophyton violaceum | bLfcin (N) | In Vitro MIC: 40 ≥ 80 μg/mL | Interaction with cell surface/alteration of cell membrane | [208] |
Trichosporon cutaneum | bLfcin (N) | In Vitro MIC: 6–18 μg/mL | Interaction with cell surface/alteration of cell membrane | [207] |
Pathogen (DNA Virus) | Source and Type of Lf/iron-Saturated Condition | Effect on Cell Viral Infection/Concentration | Other Effects In Vitro/Concentration | Ref. |
Feline herpesvirus (FHV-1) | bLf (N) | In Vitro: Inhibition of viral replication 0.5–10 mg/mL | [242] | |
Human cytomegalovirus (HCMV) | apo-bLf (N) and holo-hLf (N) | In Vitro Prevented virus adsorption and penetration into the host cells 1 mg/mL | [237] | |
apo-hLf (N), holo-hLf (N), apo-bLf(N), apo-gLf (N) and cyclic bLfcin (S) | In Vitro Prevented virus adsorption and penetration into the host cells IC50: bLf: 0.7 μM, hLf: 1.1 μM, gLf: 3.4 μM and cyclic bLfcin: 5 μM | [241] | ||
Pathogen (RNA virus) | Source and type of Lf/iron-saturated condition | Effect on cell viral infection/concentration | Other effects In Vitro/concentration | Ref. |
Chikungunya virus | apo-bLf (N) | In Vitro Prevention of viral infection IC50: 0.2 mg/mL Decreased viral replication 1.0 mg/mL | [244] | |
Hepatitis C virus (HCV) | hLf (N), cLf (N), bLf (N) and oLf (N) | In Vitro Prevented viral adsorption and penetration into host cells hLf, bLf and oLf: 0.25 and 0.5 mg/mL cLf: 100, 150, 200, 250 and 500 μg/mL | [251] | |
holo-cLf (N) | In Vitro Prevented viral adsorption and penetration into the host cells 1 mg/mL | [250] | ||
cLf (N), cLf N lobe (N), cLf C lobe (N), rcLf (S) and rcLf N lobe (S) | In Vitro Blocks viral entry/viral infection cLf and rcLf: 0.5–1.0 mg/mL Inhibition of viral replication cLf and rcLf: 0.75–1.25 mg/mL cLf N and C lobes: 0.25–1.25 mg/mL rcLf C lobe: 1.0–1.25 mg/mL | [249] | ||
Human immunodeficiency virus (HIV-1) | hLf (N) and bLf (N) | In Vitro Inhibition/prevention of viral infection IC50: hLf: 75 μg/mL bLf: 40 μg/mL | [214] | |
holo-bLf (N) and apo-bLf (N) | In Vitro Prevented viral adsorption and penetration into host cells 0–20 μg/mL | [235] | ||
apo-hLf (N), apo-bLf (N) with zidovudine | In Vitro Prevented viral adsorption and penetration into host cells IC50: apo-hLf: 9.6 μM and apo-bLf: 2.4 μM Zidovudine: 0.25–0.001 μM | [240] | ||
Herpes simplex virus-1 (HSV-1) | holo-hLf (N) and apo-bLf (N) | In Vitro Prevented viral adsorption and penetration into host cells 1 mg/mL | [237] | |
apo-hLf (N), apo-bLf (N), | In Vitro Prevented viral adsorption and penetration into host cells IC50: apo-hLf (1.41 μM) and apo-bLf (0.12 μM) | [238] | ||
bLf (N) and b-Lfcin (N) | In Vitro Prevented viral adsorption and penetration into host cells IC50: bLf: 0.6 μM, bLfcin: 14.6 μM | [243] | ||
Mayarovirus (MAYV) | apo-bLf (N) | In Vitro Prevented viral adsorption and penetration into host cells 1 mg/mL | [233] | |
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) | Liposomal bLf (S) (LactyferrinTM) | Oral supplementation LactyferrinTM: 32 mg/10 mL and vitamin C 12 mg/10 mL Dose for treatment for COVID-19 64-96 mg/6 h daily to cure COVID-19 (256–384 mg/d). Dose can be increased to 128 mg/6 h (512 mg) if needed. Preventive dose for COVID 19: 64 mg two to three times daily (128–192 mg/d). Lactyferrin syrup for pregnant women and infants (glycerosome encapsulation, alcohol free) - Pregnant women and infants under the age of two. - Mothers: 64 mg (20 mL) twice a day (128 mg/d). - Infants: 32 mg (10 mL) twice daily. - Zinc defense syrup: 10-30 mg/d (10–30 mL) LF nasal drops (Lactyferrin) to relieve acute sinusitis, alterations in smell and taste, and dry cough. In acute cases, we recommend applying two drops to each nostril every 4–6 h. | [247] | |
Simian rotavirus SA11 | apo-bLf (N), holo-bLf (N), Zn-bLf (S), Mn-bLf (S) | In Vitro Inhibition of cytopathic effect EC50: apo-bLf: 50 μg/mL holo-bLf: 46 μg/mL Zn-bLf and Mn-bLf: 62 μg/mL | [253] | |
apo-bLf (N) and holo-bLf (N) | In Vitro Prevented viral adsorption and penetration into host cells 25 μM | [239] | ||
Zika virus | apo-bLf (N) | Prevention of viral infection IC50: 0.4 mg/mL Decreased viral replication 1.0 mg/mL | [244] |
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Zarzosa-Moreno, D.; Avalos-Gómez, C.; Ramírez-Texcalco, L.S.; Torres-López, E.; Ramírez-Mondragón, R.; Hernández-Ramírez, J.O.; Serrano-Luna, J.; de la Garza, M. Lactoferrin and Its Derived Peptides: An Alternative for Combating Virulence Mechanisms Developed by Pathogens. Molecules 2020, 25, 5763. https://doi.org/10.3390/molecules25245763
Zarzosa-Moreno D, Avalos-Gómez C, Ramírez-Texcalco LS, Torres-López E, Ramírez-Mondragón R, Hernández-Ramírez JO, Serrano-Luna J, de la Garza M. Lactoferrin and Its Derived Peptides: An Alternative for Combating Virulence Mechanisms Developed by Pathogens. Molecules. 2020; 25(24):5763. https://doi.org/10.3390/molecules25245763
Chicago/Turabian StyleZarzosa-Moreno, Daniela, Christian Avalos-Gómez, Luisa Sofía Ramírez-Texcalco, Erick Torres-López, Ricardo Ramírez-Mondragón, Juan Omar Hernández-Ramírez, Jesús Serrano-Luna, and Mireya de la Garza. 2020. "Lactoferrin and Its Derived Peptides: An Alternative for Combating Virulence Mechanisms Developed by Pathogens" Molecules 25, no. 24: 5763. https://doi.org/10.3390/molecules25245763
APA StyleZarzosa-Moreno, D., Avalos-Gómez, C., Ramírez-Texcalco, L. S., Torres-López, E., Ramírez-Mondragón, R., Hernández-Ramírez, J. O., Serrano-Luna, J., & de la Garza, M. (2020). Lactoferrin and Its Derived Peptides: An Alternative for Combating Virulence Mechanisms Developed by Pathogens. Molecules, 25(24), 5763. https://doi.org/10.3390/molecules25245763