Yeast Infection - Treatment

Lactoferricin - updated: 12 March 2009

Lactoferricin, a new antimicrobial peptide

J Appl Bacteriol. 1994 Aug;77(2):208-14

Jones EM, Smart A, Bloomberg G, Burgess L, Millar MR.

Lactoferricin B (LF-B) is a peptide derived from acid-pepsin digestion of bovine lactoferrin, which has antimicrobial properties. In order to assess the antimicrobial spectrum of LF-B and its possible in vivo uses, the minimum inhibitory and microbicidal concentrations of pure lactoferricin B were determined for a range of bacterial species and under varying conditions of growth including growth phase and size of the inoculum, pH and ionic strength of the medium. Lactoferricin B was bactericidal against a wide range of bacteria and Candida albicans. Proteus spp., Pseudomonas cepacia and Serratia spp. were resistant. The bactericidal activity of LF-B was inhibited by increasing ionic strength and bacterial inoculum and at acid pH. The activity of lactoferricin B was completely inhibited by the addition of 5% whole cow's milk and was reduced in the presence of increasing concentrations of mucin. These results indicate the potential of LF-B to reduce the numbers of organisms in a simple medium, but raise doubts about its role in vivo because of its sensitivity to changes in physical variables. It may be that lactoferricin exerts a transient antimicrobial effect at mucosal surfaces.

Publication Types:

• Study

The medicinal chemistry of short lactoferricin-based antibacterial peptide

Curr Med Chem. 2007;14(1):1-18

Haug BE, Strøm MB, Svendsen JS

This review discusses antibacterial peptides from the perspective of development into clinically useful chemotherapeutic drugs using short lactoferricin based peptides as examples. The review shows how important features for antibacterial activity can be identified and explored using the molecular properties of a range of natural and non-natural amino acids. The results have been further refined quantitatively using a "soft-modelling" approach where important structural parameters that influence the antibacterial activity of 15-residue model peptides were identified. The review describes how this knowledge is utilised to generate pharmacophores for antibacterial efficacy. These pharmacophores turn out to be surprisingly small and relatively consistent between typical Gram-negative and Gram-positive bacteria leading to the discovery of a novel class of short synthetic cationic antimicrobial peptides. These compounds are found to have high antibacterial activity against several bacterial strains that are resistant to commercial antibiotics, and are promising as future clinical candidates for treatment of infections caused by several clinically relevant pathogens

Publication Types:

• Review

Fungicidal effect of three new synthetic cationic peptides against Candida albicans

Oral Dis. 2004 Jul;10(4):221-8

Nikawa H, Fukushima H, Makihira S, Hamada T, Samaranayake LP.

OBJECTIVE: Peptide antibiotics are considered a new class of antifungal agents. Of these, an alpha-helical, cationic peptide termed Dhvar 4, a relative of salivary histatin has been shown to be an antifungal of relatively high potency. Similarly, lactoferricin B (LFB) and a derivative thereof, LFB(17-30), disrupts the fungal cell membrane and acts against Candida albicans. As Dhvar 4 and LFB(17-30), exhibit almost identical amino acid sequences at their C-terminal, we hypothesized that laboratory synthesis of peptides with an alpha-helical structure and having similar amphipathic properties could lead to products with candidacidal activity. Hence, three such peptides - JH8194, JH8195 and JH 8944, were synthesized and their antifungal properties compared with recognized antifungals LFB, LFB(17-30), human lactoferricin (LFH), Histatin-5 and Dhvar 4, against two isolates of C. albicans. MATERIALS AND METHODS: The antifungal agents were synthesized and their secondary structures evaluated according to a previously described protocol of Situ and Bobek (2000)Antimicrob Agents Chemother44: 1485-1493. The C. albicans strains were oral isolates from a human immunodeficiency virus-infected (isolate A2) and a healthy (A6) individual. A standard concentration of yeasts was exposed to a range of dilutions of the agents for a specific duration and the cell death (viability) in terms of the resultant colony forming units ml(-1) was quantified. RESULTS: Dhvar 4, showed the most alpha-helical propensity, and was the least fungicidal while LFB and LFB(17-30) showed the highest antifungal potential, and demonstrated total kill of A6, and A2 at 5 and 10 microM concentrations, respectively whilst LFH killed both isolates at a l0 microM concentration. Of the three new synthetic peptides, JH 8194 was the most potent (total kill of A6/A2 strains at 1.25/2.5 microM), followed by JH 8195 (total kill of A6/A2 strains at 5/10 microM while JH 8944 was the least potent as a 25 microM concentration was required to kill either strain of Candida. On further analyses of the relationship between pI value of the peptides and their anticandicidal activity, a significant positive correlation was noted. In order to rule out a cytotoxic effect of the new synthetic peptides we compared the fungicidal and hemolytic activities under similar incubation conditions using freshly isolated erythrocytes and all three peptides exhibited no detectable hemolysis upto an concentration of 100 microM in contrast to the polyene antifungal amphotericin B that elicited significant initiation of hemolysis at a concentration of 5.0 microM. CONCLUSION: Our data suggest that laboratory synthesis of agents with an alpha-helical structure and having amphipathic properties similar to known, natural antifungal agents may be a promising avenue to generate products with improved antifungal activity

Publication Types:

• Study

Publication Types:

• Review