Mini-review: Lactoferrin: a bioinspired, anti-biofilm therapeutic

Figures & data

Figure 1 Combined treatment of P. aeruginosa biofilms with lactoferrin and xylitol results in membrane disruption. SEM imaging (panels A and B) and LIVE/DEAD staining (panels C and D) demonstrate significant membrane disruption of treated cells (panels B and D) when compared to untreated cells (panels A and C). For more information see Ammons, Ward and James (2011) and Ammons, Ward, Dowd et al. (2011).

Table 1. Antimicrobial efficacy of lactoferrin and peptide derivatives against MRSA in vitro and in vivo.

Peptide residues	Sequence	In vitro lethality IC50 (M)	In vivo lethality IC50 (mol mouse^−1)
hLf	692 amino acids	7.0	4.3
hLf (1–11)	GRRRRSVQWCA	2.9	1.2
hLf (4–11)	RRSVQWCA	68.0	17.4
hLf (21–31)	FQWQRNMRKVR	21.0	8.9
Note: Adapted from Yamauchi et al. (1993).

Figure 2 SEM image showing an undifferentiated HL60 human monocytic cell which has come up against a wall of P. aeruginosa and S. aureus cells co-cultured in a biofilm grown in vitro.

Table 2. Selection of clinical trials using lactoferrin and/or peptide derivatives.

Status	Title	Identifier
Not yet recruiting	Lactoferrin for prevention of sepsis in infants	NCT01525316
Active	Pilot study: lactoferrin for prevention of neonatal sepsis	NCT01264536
Completed	Randomized, controlled trial – lactoferrin prevention of diarrhea in children	NCT00560222
Recruiting	Bovine lactoferrin as a natural regimen of selective decontamination of the digestive tract in patients with prolonged mechanical ventilation	NCT01535170
Unknown	Use of recombinant human lactoferrin in long-term care patients with feeding tubes with clostridium difficile	NCT00377078
Not yet recruiting	Recombinant human lactoferrin administered orally for the prevention of antibiotic associated diarrhea in adult patients	NCT01382199
Completed	Safety of a single dose of 5 mg of hlf1-11 given to autologous haematopoietic stem cell transplant recipients	NCT00509938
Completed	Safety and efficacy study of recombinant human lactoferrin to treat severe sepsis	NCT00630656
Recruiting	Study of talactoferrin oral solution for nosocomial infection in preterm infants	NCT00854633
Recruiting	Talactoferrin in treating patients with relapsed or refractory non-small cell lung cancer or squamous cell head and neck cancer	NCT01528137
Note: Adapted from www.clinicaltrials.gov.

Ammons , MC , Ward , LS and James , GA . 2011 . Anti-biofilm efficacy of a lactoferrin/xylitol wound hydrogel used in combination with silver wound dressings . Int Wound J , 8 : 268 – 273 .

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Ammons , MC , Ward , LS , Dowd , S and James , GA . 2011 . Combined treatment of Pseudomonas aeruginosa biofilm with lactoferrin and xylitol inhibits the ability of bacteria to respond to damage resulting from lactoferrin iron chelation . Int J Antimicrob Agents , 37 : 316 – 323 .

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Yamauchi , K , Tomita , M , Giehl , TJ and Ellison , RT 3rd . 1993 . Antibacterial activity of lactoferrin and a pepsin-derived lactoferrin peptide fragment . Infect Immun , 61 : 719 – 728 .

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