Effect of bovine lactoferricin on enteropathogenic Yersinia adhesion and invasion in HEp-2 cells

Abstract

Bovine lactoferricin, a pepsin-generated antimicrobial peptide from bovine lactoferrin active against a wide range of bacteria, was tested for its ability to influence the adhesion and invasion of Yersinia enterocolitica and Yersinia pseudotuberculosis in HEp-2 cells. The addition of non-cytotoxic and non-bactericidal concentrations of lactoferricin to cell monolayers before infection, under different bacterial growth experimental conditions, was ineffective or resulted in about a 10-fold increase in bacterial adhesion, whereas, in bacteria grown in conditions allowing maximal inv gene expression, a 10-fold inhibition of cell invasion by lactoferricin was observed. To confirm that the anti-invasive activity of lactoferricin was exerted against invasin-mediated bacterial entry, experiments were also performed utilizing Escherichia coli strain HB101 (pRI203), harbouring the inv gene from Y. pseudotuberculosis, which allows penetration of mammalian cells. Under these experimental conditions, lactoferricin was able to inhibit bacterial entry into epithelial cells, demonstrating that this peptide acts on inv-mediated Yersinia species invasion. As the inv gene product is the most important virulence factor in enteropathogenic Yersinia, being responsible for bacterial adherence and penetration within epithelial cells of the intestinal lumen and for the subsequent colonization of regional lymph nodes, these data provide additional information on the protective role of lactoferricin against bacterial infection.

The Antimicrobial Effect of Lactoferrin on Gram-Negative and Gram-Positive Bacteria

“…Other enteropathogens have similar complex interactions with lactoferrin. Lactoferrin has antibacterial activity and its iron-binding mechanism can destroy the bacteria (13). Apolactoferrin (iron-free lactoferrin) increases the permeability of the bacterial membrane by directly damaging the outer membrane of Gram-negative bacteria (14)(15)(16).…”

Lactoferricin B Inhibits the Phosphorylation of the Two-Component System Response Regulators BasR and CreB

“…Lfcin B was confirmed to inhibit the growth of bacteria including Salmonella and E. coli (56 -58). Additionally, Lfcin B was able to reduce the adhesion to and invasion of host cells by Yersinia (59). However, the homologous examination of BasR and CreB in probiotics, including Bifidobacterium and Lactobacillus (supplemental Fig.…”

Effect of lactoferrin on enteric pathogens

“…Lactoferrin thus decreases virulence of some of the major enteropathogens by interfering with surface-expressed virulence factors. For example, bovine lactoferrin inhibits Yersina spp entry into epithelial cells [26] and induces apoptosis [27]. Other bacterial enteropathogens likewise have complex interactions with lactoferrin.…”