Lactoferrin: A Critical Mediator of Both Host Immune Response and Antimicrobial Activity in Response to Streptococcal Infections

Lu, Jacky; Francis, Jamisha D.; Doster, Ryan S.; Haley, Kathryn P.; Craft, Kelly M.; Moore, Rebecca E.; Chambers, Schuyler A.; Aronoff, David M.; Osteen, Kevin G.; Damo, Steven M.; Manning, Shannon D.; Townsend, Steven D.; Gaddy, Jennifer A.

doi:10.1021/acsinfecdis.0c00050

Cited by 29 publications

(20 citation statements)

References 114 publications

(233 reference statements)

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“…The antimicrobial activity of lactoferrin has been implicated in many bacterial species, as well as viruses, and fungi [32] . Our previous work demonstrated that recombinant lactoferrin could inhibit GBS growth via iron chelation.…”

Section: Discussionmentioning

confidence: 98%

“…In a systematic review of available literature, enteral lactoferrin supplementation decreases late‐onset sepsis and in combination with probiotics, may decrease necrotizing enterocolitis in preterm infants [31] . Lactoferrin also shows promise as an agent against streptococcal infections, [32] including a study demonstrating lactoferrin decreases biofilm formation in Streptococcus mutans [33] . Biofilms are multicellular structures that are critical for many bacterial pathogens, including GBS, to circumnavigate host defenses and persist in the hostile environment [34,35] .…”

Section: Introductionmentioning

confidence: 99%

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

Francis

Guevara

et al. 2021

ChemBioChem

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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.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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

Francis

Guevara

et al. 2021

ChemBioChem

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“…LF kills pathogenic microorganisms by competitively seizing iron to lack sufficient iron replenishment to maintain biofilm structure and consequently die (51). LF binds to lipopolysaccharide (LPS) on the cell wall of gram-negative bacteria, killing the bacteria by altering cell membrane permeability (52,53). LF also has antiviral activity, preventing viruses from entering the host cell by blocking cellular receptors or directly binding to the virion (54).…”

Section: Lactoferrin (Lf)-lpn Complexmentioning

confidence: 99%

A literature review on lactopontin and its roles in early life

Jia¹,

Zhu²,

Yu³

et al. 2021

Transl Pediatr

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Objective: Our study aims to review the functions and possible mechanisms of lactopontin (LPN) in early life.Background: Human milk proteins provide a variety of protection and health benefits in early life. One of these multifunctional proteins is LPN, which is osteopontin (OPN) derived from milk.Methods: Information used to write this paper was collected from Uniprot, PubMed, and Google Scholar, including in vitro, in vivo, and clinical studies.Conclusions: LPN is a highly phosphorylated, O-glycosylated acidic protein and a unique type of OPN, as it presents at the highest concentration and a higher degree of posttranslational modifications (PTMs) in human milk than other tissues and excretions. LPN is present in milk and the intestinal tracts of infants after consumption as a mixture of intact protein and peptides, which can bind diverse integrin and receptors in the target cell and drive downstream signaling pathways. LPN is found to play important roles in developing the immune, intestinal and nervous systems in early life. Moreover, LPN has also shown to support preterm infants' health when they are especially vulnerable after delivery via animal studies. Additionally, LPN can form protein complex with another milk bioactive protein, lactoferrin (LF), to withstand proteolysis and perform more efficient biological activity. Therefore, LPN showed great potential for early life while more clinical trials and evidence are still emergying.

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“…Lactoferrin is an iron-sequestering glycoprotein with antimicrobial properties that is highly expressed in milk during bovine mastitis (Harmon et al, 1976;Hagiwara et al, 2003;Chaneton et al, 2008). Due to its abundance and importance in host defense, many bacterial pathogens have evolved mechanisms for interacting with lactoferrin (Valenti and Antonini, 2005;Lu et al, 2020). S. uberis encodes two lactoferrin-binding proteins that demonstrate preference for bovine lactoferrin, in comparison to the human variant, and promote evasion of the antimicrobial properties of lactoferrin in the mammary gland niche (Fang and Oliver, 1999;Moshynskyy et al, 2003).…”

Section: Streptococcus Uberis Adhesion Moleculementioning

confidence: 99%

The Role of Gram-Positive Surface Proteins in Bacterial Niche- and Host-Specialization

Pickering

Fitzgerald

2020

Front. Microbiol.

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Gram-positive bacterial pathogens have an array of proteins on their cell surface that mediate interactions with the host environment. In particular, bacterial cell wallassociated (CWA) proteins play key roles in both colonization and pathogenesis. Furthermore, some CWA proteins promote specialization for host-species or mediate colonization of specific anatomical niches within a host. In this mini review, we provide examples of the many ways by which major pathogens, such as Staphylococci, Streptococci and Listeria monocytogenes, utilize CWA proteins for both host-and niche-specialization. We describe different biological mechanisms mediated by CWA proteins including: the acquisition of iron from hemoglobin in the bloodstream, adherence to and invasion of host cells, and innate immune evasion through binding to the plasma proteins fibrinogen, immunoglobulin G, and complement. We also discuss the limitations of using animal models for understanding the role of specific CWA proteins in host-specialization and how transformative technologies, such as CRISPR-Cas, offer tremendous potential for developing transgenic models that simulate the host environment of interest. Improved understanding of the role of CWA proteins in nicheor host-specificity will allow the design of new therapeutic approaches which target key host-pathogen interactions underpinning Gram-positive bacterial infections.

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Lactoferrin: A Critical Mediator of Both Host Immune Response and Antimicrobial Activity in Response to Streptococcal Infections

Cited by 29 publications

References 114 publications

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

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

A literature review on lactopontin and its roles in early life

The Role of Gram-Positive Surface Proteins in Bacterial Niche- and Host-Specialization

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