Lactoferrin and Its Derived Peptides: An Alternative for Combating Virulence Mechanisms Developed by Pathogens Original paper

What was reviewed?

This comprehensive review examined the multifaceted antimicrobial and immunomodulatory roles of lactoferrin (Lf) and its derived peptides. It synthesized mechanistic and preclinical findings that demonstrate how Lf and its peptides inhibit the virulence traits of a broad array of bacterial, fungal, viral, and parasitic pathogens. Particular focus was given to how Lf interferes with microbial adhesion, invasion, toxin production, biofilm formation, immune evasion strategies, and key mechanisms in host colonization and disease progression.

Who was reviewed?

The paper reviewed mechanistic studies, in vitro experiments, and in vivo models involving diverse pathogens, including Escherichia coli, Pseudomonas aeruginosa, Streptococcus pneumoniae, Giardia lamblia, Entamoeba histolytica, Cryptosporidium parvum, and multiple other bacterial and parasitic species. Both human and bovine sources of Lf, in apo- and holo-forms, were discussed, along with enzymatically derived and synthetic peptide variants.

What were the most important findings?

Lactoferrin and its peptides disrupt virulence by targeting microbial membranes, destabilizing surface structures, inhibiting iron uptake, and modulating gene expression linked to biofilm and toxin production. Apo-Lf acts as both a microbiostatic and microbicidal agent, chelating iron and causing membrane destabilization, while Lfcins exhibit potent direct antimicrobial activity independent of iron binding. Lf and its peptides suppress adhesion of pathogens to epithelial cells, block colonization, and interfere with secretion of critical virulence factors like pyocyanin, elastase, leukotoxin, and Shiga toxin.

In the microbiome context, this selective action helps control overgrowth of pathogens without disrupting commensal populations. Lf and Lfcins inhibit biofilm formation in resistant species like P. aeruginosa, K. pneumoniae, and S. pneumoniae, while promoting epithelial integrity and mitigating inflammation. Importantly, Lf and peptides show synergistic activity with antibiotics, restoring sensitivity in multidrug-resistant bacteria, which supports their integration into microbiome-preserving antimicrobial strategies.

What are the implications of this review?

This review positions lactoferrin and its peptides as promising natural alternatives or adjuncts to traditional antimicrobials, particularly for addressing virulence rather than simply killing pathogens. By targeting biofilms, adhesins, toxins, and iron acquisition systems—without broad-spectrum bactericidal activity—Lf interventions reduce pathogen fitness while maintaining microbial community balance. For clinicians, these agents could support the treatment of infections resistant to conventional antibiotics and preserve the microbiome during therapy. The multifactorial action and synergy with antibiotics make Lf-derived peptides strong candidates for next-generation antimicrobials in microbiome-sensitive applications.