In milk and colostrum, the primary iron-binding protein is lactoferrin. Lactoferrin has two iron binding sites per molecule. Lactoferrin is inhibitory by itself to a number of microorganisms including Bacillus subtilis, B. stearothermophilus, Listeria monocytogenes, Micrococcus species, E. coli and Klebsiella species (Oram and Reiter, 1968; Korhonen, 1978; Reiter, 1978; Mandel and Ellison, 1985; Payne et al., 1990). The compound has no activity against Salmonella Typhimurium, Pseudomonas fluorescens and little activity against E. coli O157:H7 or L. monocytogenes VPHI (Payne et al., 1994). Some gram-negative bacteria may be resistant because they adapt to low iron environments by producing siderophores such as phenolates and hydroxamates (Ekstrand, 1994). Microorganisms with a low iron requirement, such as lactic acid bacteria, would not be inhibited by lactoferrin. Since it is cationic, lactoferrin may increase the outer membrane permeability to hydrophobic compounds, including other antimicrobials. According to Naidu and Bidlack (1998), lactoferrin blocks adhesion of microorganisms to mucosal surfaces, inhibits expression of fimbria and other colonizing factors of enteric pathogens, such as E. coli, and inactivates lipopolysaccharides of gramnegative bacteria.

Lactoferricin B or hydrolyzed lactoferrin (HLF) is a small peptide produced by acid-pepsin hydrolysis of bovine lactoferrin (Bellamy et al., 1992). Jones et al. (1994) reported that the compound was inhibitory to Shigella, Salmonella, Yersinia enterocolitica, E. coli 0157:H7, S. aureus, L. monocytogenes and Candida. In contrast, while HLF was effective against L. monocytogenes, Enterohemorrhagic E. coli, and Salmonella Enteritidis in peptone yeast extract glucose broth, it was not active in a more complex medium, trypticase soy broth (TSB) (Branen and Davidson, 2000). The addition of EDTA enhanced the activity of HLF in TSB, indicating that the decreased activity of HLF may have been due, in part, to excess cations in the medium. Venkitanarayanan et al. (1999) found that, while 50 or 100 pg lactoferricin B per ml reduced viable E. coli 0157:H7 in 1% peptone, it was much less effective as an antimicrobial in ground beef.

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