**3.2 Antimicrobial activities**

Except lactoferrin, the major milk proteins do not exhibit any antimicrobial activity in their native state even at high concentrations [63, 64].

Indeed, lactoferrin belongs to the protein family of transferrin family. It presented an activity against a wide spectrum of pathogenic microorganisms for humans. For instance, lactoferrin exerts a bacteriostatic and bactericidal effect on various Gram-negative bacteria such as *E. coli*, *Salmonella*, *Ps. aeuruginosa*, *H. pylori*, *Enterobacter*, *Yersinia*, *Porphyromonas gingivalis* and *Klebsiella pneumoniae*. Besides, this protein had antibacterial activities against Gram-positive bacteria such as *Listeria monocytogenes*, *Bacillus* and *S. aureus* [65]. Likewise, lactoferrin has been used against different yeasts such as *C. dubliniensis*, *C. albicans*, *C. glabrata*, and *Cryptococcus*, in synergy with different antifungal drugs [66]. In this context, several mechanisms of action of lactoferrin have been demonstrated against bacteria, fungi, parasites and viruses, including possible activity against the novel coronavirus SARS-CoV-2 infection [67].

On the contrary, pure β-casein and α-lactalbumin (apo and holo forms) had no bactericidal activity against *Escherichia coli, Staphylococcus aureus Enterococcus faecalis* and *Pseudomonas aeruginosa*. Furthermore, these proteins had no antifungal activity against, *Aspergillus tamarii, Aspergillus sclerotiorum Aspergillus protuberus* and *Penicillium bilaiae* even at a concentration of 5 g/l [42, 50]. However, pure proteins of milk from other mammalian species as goat and camel exhibited significant antimicrobial activities. For instance, apo camel α-lactalbumin showed moderate antimicrobial activities towards *Pseudomonas aeruginosa, Penicillium bilaiae, Aspergillus tamari* and *Aspergillus sclerotiorum* [50]. Furthermore, camel β-casein had strong antifungal activities against *Aspergillus tamarii* and *Aspergillus sclerotiorum* [42]. Meanwhile, the αS2-casein from goat milk had antimicrobial effects against Gram-positive and Gram-negative bacteria, including *Bacillus cereus Escherichia coli*, *Listeria monocytogenes*, *Salmonella typhi*, *Staphylococcus aureus*, and *Shigella flexneri* [68].

The same trends were reported for native caseins which exhibited no antimicrobial activity: caseins just release bioactive peptides after digestion presenting these activities [69]. Once these peptides are released, they can act as regulatory compounds in the host organism with specific biological activities such as antioxidant and antimicrobial activities [70]. Similarly, four peptide fragments were yielded after a proteolytic digestion of the β-lactoglobulin by trypsin. These peptides exerted bactericidal activity against Gram-positive bacteria only [71]. However, generated peptides of β-lactoglobulin through the action of other enzymes such as alcalase, pepsin or trypsin, have been shown to be bacteriostatic against pathogenic strains of *E. coli*, *Bacillus subtilis* and *Staphylococcus aureus* [63].

On the other hand, previous works noted that the trypsin enzymatic treatment of α-lactalbumin led to the release of peptides with antibacterial activities. However, only one antibacterial peptide was generated after a treatment using the chymotrypsin enzyme. These peptides are known by their activity against Gram-positive bacteria, whereas, weaker effects were detected with Gram-negative bacteria. Overall, the peptides obtained from the α-lactalbumin after pepsin or trypsin treatments inhibited the growth of *E. coli*. However, pepsin treatment did not release any antibacterial peptides from the α-lactalbumin [63, 72].

*Promising Food Ingredients: Milk Proteins DOI: http://dx.doi.org/10.5772/intechopen.99092*
