Diverse Mechanisms of Antimicrobial Activities of Lactoferrins, Lactoferricins, and Other Lactoferrin-Derived Peptides

Abstract

Lactoferrins are an iron-binding glycoprotein that have important protective roles in the mammalian body through their numerous functions, which include antimicrobial, antitumor, anti-inflammatory, immunomodulatory, and antioxidant activities. Among these, their antimicrobial activity has been the most studied, although the mechanism behind antimicrobial activities remains to be elucidated. Thirty years ago, the first lactoferrin-derived peptide was isolated and showed higher antimicrobial activity than the native lactoferrin lactoferricin. Since then, numerous studies have investigated the antimicrobial potencies of lactoferrins, lactoferricins, and other lactoferrin-derived peptides to better understand their antimicrobial activities at the molecular level. This review defines the current antibacterial, antiviral, antifungal, and antiparasitic activities of lactoferrins, lactoferricins, and lactoferrin-derived peptides. The primary focus is on their different mechanisms of activity against bacteria, viruses, fungi, and parasites. The role of their structure, amino-acid composition, conformation, charge, hydrophobicity, and other factors that affect their mechanisms of antimicrobial activity are also reviewed.

Antimicrobial and Prebiotic Activity of Lactoferrin in the Female Reproductive Tract: A Comprehensive Review

“…LF may also accelerate the repair processes of damaged tissues and wounds [ 5 , 6 , 7 , 8 ]. Significantly, LF-derived peptides that are generated upon enzymatic degradation, for example, lactoferricin, also demonstrate similar or even higher activity than the native protein [ 25 , 26 ]. This is relevant when taking into account the partial digestion of LF in the gastrointestinal tract and other tissues, during ongoing inflammation or infection.…”

Antimicrobial Peptides in Early-Life Host Defense, Perinatal Infections, and Necrotizing Enterocolitis—An Update

“…Human milk is an important source of AMPs that play a central role in hosts’ innate intestinal defense and in the development of NEC, especially form preterm neonates who are at high risk for both sepsis and NEC [ 86 , 87 ]. Several AMPs are produced in the gut following proteolysis and the fermentation of milk proteins (e.g., casein, a-lactalbumin, lactoferrin, and lysozyme; see Table 2 ) [ 17 , 86 , 87 , 88 , 89 , 90 , 91 ]. Additionally, HNP-1 and -2, HD-5 and HD-6, HBD-1 to -4, and LL-37 have been identified in human milk and colostrum [ 36 , 86 , 87 , 92 ].…”

Mammals' humoral immune proteins and peptides targeting the bacterial envelope: from natural protection to therapeutic applications against multidrug‐resistant Gram‐negatives

“…Another example of a protein precursor that can produce different CAMPs depending on the proteolytic process is lactoferrin, which is a secreted globular glycoprotein (≈80 kDa) with an iron sequestration‐based (non‐cell wall lytic) antimicrobial activity (Cutone et al ., 2019 ; Gruden & Poklar Ulrih, 2021 ). Besides the two bacterial envelope‐targeting peptides obtained from lactoferrin by artificial digestion (LF1‐11 and lactoferrampin, see Section III .2 b.iv ), the loop‐structured lactoferricin is naturally released mainly through proteolysis by host pepsin (Bellamy et al ., 1992 ; Van Der Kraan et al ., 2004 ; Bruni et al ., 2016 ; Amerikova et al ., 2019 ).…”