ArticlePLoS genetics2016
Antimicrobial Functions of Lactoferrin Promote Genetic Conflicts in Ancient Primates and Modern Humans.
Article in PLoS genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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Who cites it
14 citing papers in PubMed, 26 citations in OpenAlex.
- Retracing the origin and evolution of a cryptic antimicrobial peptide within mammalian lactoferrin.PLoS biology · 2026Article
- Mechanisms of host adaptation by bacterial pathogens.FEMS microbiology reviews · 2024Review
- Dynamic Evolution of Bacterial Ligand Recognition by Formyl Peptide Receptors.Genome biology and evolution · 2023Article
- Molecular de-extinction of ancient antimicrobial peptides enabled by machine learning.Cell host & microbe · 2023Article
- Targeting bacterial transferrin and lactoferrin receptors for vaccines.Trends in microbiology · 2022Review
- Lactoferrin: A glycoprotein that plays an active role in human health.Frontiers in nutrition · 2022Review
- Molecular Evolution of Transition Metal Bioavailability at the Host-Pathogen Interface.Trends in microbiology · 2021Review
- Battlefronts of evolutionary conflict between bacteria and animal hosts.PLoS pathogens · 2020Article
- Lactoferrin is a dynamic protein in human melioidosis and is a TLR4-dependent driver of TNF-α release in Burkholderia thailandensis infection in vitro.PLoS neglected tropical diseases · 2020Article
- Lactoferrin: A Critical Mediator of Both Host Immune Response and Antimicrobial Activity in Response to Streptococcal Infections.ACS infectious diseases · 2020Review
- Molecular Basis for the Evolution of Species-Specific Hemoglobin Capture by Staphylococcus aureus.mBio · 2018Article
- The Diversity of Mammalian Hemoproteins and Microbial Heme Scavengers Is Shaped by an Arms Race for Iron Piracy.Frontiers in immunology · 2018Article
- Lactoferrin in a Context of Inflammation-Induced Pathology.Frontiers in immunology · 2017Review
- Transition Metals and Virulence in Bacteria.Annual review of genetics · 2016Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Lactoferrin is a multifunctional mammalian immunity protein that limits microbial growth through sequestration of nutrient iron. Additionally, lactoferrin possesses cationic protein domains that directly bind and inhibit diverse microbes. The implications for these dual functions on lactoferrin evolution and genetic conflicts with microbes remain unclear. Here we show that lactoferrin has been subject to recurrent episodes of positive selection during primate divergence predominately at antimicrobial peptide surfaces consistent with long-term antagonism by bacteria. An abundant lactoferrin polymorphism in human populations and Neanderthals also exhibits signatures of positive selection across primates, linking ancient host-microbe conflicts to modern human genetic variation. Rapidly evolving sites in lactoferrin further correspond to molecular interfaces with opportunistic bacterial pathogens causing meningitis, pneumonia, and sepsis. Because microbes actively target lactoferrin to acquire iron, we propose that the emergence of antimicrobial activity provided a pivotal mechanism of adaptation sparking evolutionary conflicts via acquisition of new protein functions.
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Registered trials
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