Antibacterial and Anti‐biofilm Activity of the Human Breast Milk Glycoprotein Lactoferrin against Group B Streptococcus

Abstract

Group B Streptococcus (GBS) is an encapsulated Gram‐positive human pathogen that causes invasive infections in pregnant hosts and neonates, as well as immunocompromised individuals. Colonization of the human host requires the ability to adhere to mucosal surfaces and circumnavigate the nutritional challenges and antimicrobial defenses associated with the innate immune response. Biofilm formation is a critical process to facilitate GBS survival and establishment of a replicative niche in the vertebrate host. Previous work has shown that the host responds to GBS infection by producing the innate antimicrobial glycoprotein lactoferrin, which has been implicated in repressing bacterial growth and biofilm formation. Additionally, lactoferrin is highly abundant in human breast milk and could serve a protective role against invasive microbial pathogens. This study demonstrates that human breast milk lactoferrin has antimicrobial and anti‐biofilm activity against GBS and inhibits its adherence to human gestational membranes. Together, these results indicate that human milk lactoferrin could be used as a prebiotic chemotherapeutic strategy to limit the impact of bacterial adherence and biofilm formation on GBS‐associated disease outcomes.

The Innate Immune Glycoprotein Lactoferrin Represses the Helicobacter pylori cag Type IV Secretion System

“…H . pylori cells have not been observed to synthesize siderophores, however they do produce a variety of siderophore receptors and iron acquisition functions, including lactoferrin and transferrin receptors which are highly expressed in iron‐deficient conditions, [28] which could aid in this process in vivo .…”

“…pylori virulence. Our group has also demonstrated that lactoferrin possesses antimicrobial properties against other bacterial pathogens such as Streptococcus agalactiae (Group B Streptococcus) [28] and Acinetobacter baumannii [36] through the conserved immune strategy of nutritional immunity.…”

“…Iron‐bound (holo‐) or unbound (apo‐) lactoferrin was prepared as previously described [8,28,29] . Briefly, a 10 mM stock of recombinant lactoferrin (Sigma Aldrich) was dialyzed against either 0.1 M sodium citrate‐bicarbonate buffer (pH 8.2) alone to generate apo‐lactoferrin, or 0.1 M sodium citrate‐bicarbonate buffer (pH 8.2) containing 70 mM ferric chloride to generate holo‐lactoferrin.…”

Analysis of Susceptibility to the Antimicrobial and Anti-Biofilm Activity of Human Milk Lactoferrin in Clinical Strains of Streptococcus agalactiae With Diverse Capsular and Sequence Types

“…Human lactoferrin was isolated from breast milk as previously described ( Lu et al., 2021 ). Briefly, expressed human breast milk was gathered from 17 healthy donors between 3 days and 3 months post-partum and stored between -80 and -20˚C.…”

“…Lactoferrin is a glycoprotein that contains two iron binding sites ( Weinberg, 1975 ) and was shown to have antimicrobial activity against a wide range of bacterial, viral, and fungal pathogens ( Lu et al., 2020 ). Indeed, our previous study demonstrated that human breast milk lactoferrin has antimicrobial and anti-biofilm activity against GBS and inhibits some GBS strains from adhering to human gestational membranes ( Lu et al., 2021 ). In this study, we advanced our findings by analyzing the antimicrobial and anti-biofilm effects of lactoferrin against a larger panel of clinical GBS strains that vary by capsular serotype, ST, isolation source, and clinical presentation.…”