• molecular ecology
• ecology
• carbohydrates

• Anthozoa/genetics
• Anthozoa/metabolism
• Anthozoa/classification
• Animals
• Phylogeny
• Mucus/chemistry
• Mucus/metabolism
• Carbohydrates/analysis
• Carbohydrates/chemistry
• Monosaccharides/analysis

• basis funding Universität Bremen
• basis funding Universität Bremen
• Wi 2677/16-1 Deutsche Forschungsgemeinschaft
• HE 7217/1-1 Deutsche Forschungsgemeinschaft
• Wi 2677/16-1 Deutsche Forschungsgemeinschaft
• 894645 H2020 Marie Skłodowska-Curie Actions
• EXC-2077-390741603 Cluster of Excellence Initiative
• Universität Bremen (1013)

• galactofuranosidase
• neoglycoprotein
• neolectin bioengineering
• site-directed mutagenesis

• Animals
• Aspergillus/metabolism
• Aspergillus/genetics
• Galactose/analogs & derivatives
• Galactose/metabolism
• Galactose/chemistry
• Glycoproteins/chemistry
• Glycoproteins/metabolism
• Lectins/metabolism
• Lectins/chemistry
• Mannans/chemistry
• Serum Albumin, Bovine/chemistry
• Disaccharides/chemistry

• APR IR NeoLect Region Centre Val de Loire

• T cell receptor repertoire
• blood vessel graft
• xenotransplantation
• γδ T cells

• Animals
• Male
• Heterografts
• Primates
• Receptors, Antigen, T-Cell
• Swine
• T-Lymphocyte Subsets
• Transplantation, Heterologous
• Macaca fascicularis

• The Bio and Medical Technology Development Program of National Research Foundation
• NRF-2020M3A9D3080110 Ministry of Science and ICT of Korea
• NRF-2020M3A9D3080107 Ministry of Science and ICT of Korea
• Korea Basic Science Institute (National Research Facilities and Equipment Center
• 2020R1A6C101A191 Ministry of Education of Korea

• Th2 response
• acquired tick resistance
• alpha-Gal
• alpha-Gal syndrome
• glycosylation
• tick saliva

• Humans
• Animals
• Ticks
• Tick Bites/complications
• Sugars
• Food Hypersensitivity/etiology
• Polysaccharides

• R21 AI128182 NIAID NIH HHS

• Enzyme activity
• Evolution
• Sialic acid
• Sialyltransferase
• Structure-function

• Animals
• Humans
• Sialyltransferases/metabolism
• Sialic Acids/metabolism
• Vertebrates/metabolism
• Glycoproteins/chemistry
• Evolution, Molecular

• Agence Nationale de la Recherche
• Ligue Contre le Cancer

• FBLD
• STD NMR
• antimicrobial
• inhibitors of pathogenic bacterial enzymes
• multidrug resistance
• phenotypic screens

Lactoferrin is a multifunctional protein that exhibits anti-inflammatory, immune regulating and anti-infective properties. One of its receptor sites is located on severe acute respiratory syndrome coronavirus 2. The binding of lactoferrin with heparin sulfate proteoglycans may prevent the first contact between the virus and host cells, thus preventing subsequent infection. Given that lactoferrin may act as a natural mucosal barrier, an intranasal treatment together with its oral intake can be hypothesized to prevent the spread, infection and inflammation caused by coronavirus disease 2019 (COVID-19). Moreover, the literature reports that vitamin D plays an essential role in promoting immune response. With its anti-inflammatory and immunoregulatory properties, vitamin D is critical for activating the immune system’s defenses, improving immune cell function. Different studies also demonstrate that lactoferrin is a potential activator of the vitamin D receptor. In this sense, the combined use of lactoferrin (through an association of oral intake and a nasal spray formulation) and vitamin D could represent a valuable therapy for COVID-19 treatment and prevention. However, further randomized clinical trials are needed before recommending/prescribing them.

• Lactoferrin
• Vitamin D
• SARS-CoV-2
• COVID-19
• Pandemics

The present investigation focuses on the analysis of the interactions among human lactoferrin (LF), SARS-CoV-2 receptor-binding domain (RBD) and human angiotensin-converting enzyme 2 (ACE2) receptor in order to assess possible mutual interactions that could provide a molecular basis of the reported preventative effect of lactoferrin against CoV-2 infection. In particular, kinetic and thermodynamic parameters for the pairwise interactions among the three proteins were measured via two independent techniques, biolayer interferometry and latex nanoparticle-enhanced turbidimetry. The results obtained clearly indicate that LF is able to bind the ACE2 receptor ectodomain with significantly high affinity, whereas no binding to the RBD was observed up to the maximum “physiological” lactoferrin concentration range. Lactoferrin, above 1 µM concentration, thus appears to directly interfere with RBD–ACE2 binding, bringing about a measurable, up to 300-fold increase of the K_D value relative to RBD–ACE2 complex formation.

• SARS-CoV-2 receptor-binding domain (RBD)
• angiotensin-converting enzyme 2 (ACE2)
• biolayer interferometry
• kinetic analysis
• lactoferrin
• nanoparticle enhanced turbidimetry

• Angiotensin-Converting Enzyme 2/antagonists & inhibitors
• Angiotensin-Converting Enzyme 2/metabolism
• COVID-19/metabolism
• COVID-19/virology
• Humans
• Lactoferrin/metabolism
• Peptidyl-Dipeptidase A/metabolism
• Protein Interaction Domains and Motifs
• SARS-CoV-2/metabolism
• Spike Glycoprotein, Coronavirus/metabolism

Carbohydrate‐binding proteins (lectins) are auspicious targets in drug discovery to combat antimicrobial resistance; however, their non‐carbohydrate drug‐like inhibitors are still unavailable. Here, we present a druggable pocket in a β‐propeller lectin BambL from Burkholderia ambifaria as a potential target for allosteric inhibitors. This site was identified employing ¹⁹F NMR fragment screening and a computational pocket prediction algorithm SiteMap. The structure–activity relationship study revealed the most promising fragment with a dissociation constant of 0.3±0.1 mM and a ligand efficiency of 0.3 kcal mol⁻¹ HA⁻¹ that affected the orthosteric site. This effect was substantiated by site‐directed mutagenesis in the orthosteric and secondary pockets. Future drug‐discovery campaigns that aim to develop small molecule inhibitors can benefit from allosteric sites in lectins as a new therapeutic approach against antibiotic‐resistant pathogens.

• NMR spectroscopy
• allostery
• carbohydrate-protein interactions
• drug discovery
• fragment-based drug design

Human milk oligosaccharides (HMOs) are non-digestible and structurally diverse complex carbohydrates that are highly abundant in human milk. To date, more than 200 different HMO structures have been identified. Their concentrations in human milk vary according to various factors such as lactation period, mother’s genetic secretor status, and length of gestation (term or preterm). The objective of this review is to assess and rank HMO concentrations from healthy mothers throughout lactation at a global level. To this aim, published data from pooled (secretor and non-secretor) human milk samples were used. When samples were reported as secretor or non-secretor, means were converted to a pooled level, using the reported mean of approximately 80/20% secretor/non-secretor frequency in the global population. This approach provides an estimate of HMO concentrations in the milk of an average, healthy mother independent of secretor status. Mean concentrations of HMOs were extracted and categorized by pre-defined lactation periods of colostrum (0–5 days), transitional milk (6–14 days), mature milk (15–90 days), and late milk (>90 days). Further categorizations were made by gestational length at birth, mother’s ethnicity, and analytical methodology. Data were excluded if they were from preterm milk, unknown sample size and mothers with any known disease status. A total of 57 peer-reviewed articles reporting individual HMO concentrations published between 1996 and 2020 were included in the review. Pooled HMO means reported from 31 countries were analyzed. In addition to individual HMO concentrations, 12 articles reporting total HMO concentrations were also analyzed as a basis for relative HMO abundance. Total HMOs were found as 17.7 g/L in colostrum, 13.3 g/L in transitional milk, and 11.3 g/L in mature milk. The results show that HMO concentrations differ largely for each individual HMO and vary with lactation stages. For instance, while 2′-FL significantly decreased from colostrum (3.18 g/L ± 0.9) to late milk (1.64 g/L ± 0.67), 3-FL showed a significant increase from colostrum (0.37 g/L ± 0.1) to late milk (0.92 g/L ± 0.5). Although pooled human milk contains a diverse HMO profile with more than 200 structures identified, the top 10 individual HMOs make up over 70% of total HMO concentration. In mature pooled human milk, the top 15 HMOs in decreasing order of magnitude are 2′-FL, LNDFH-I (DFLNT), LNFP-I, LNFP-II, LNT, 3-FL, 6′-SL, DSLNT, LNnT, DFL (LDFT), FDS-LNH, LNFP-III, 3′-SL, LST c, and TF-LNH.

• 2′-fucosyllactose
• HMO composition
• human milk carbohydrates
• human milk oligosaccharides
• non-digestible carbohydrates

Glycolipids are present on the surfaces of all living cells and thereby represent targets for many protein receptors, such as lectins. Understanding the interactions between lectins and glycolipids is essential for investigating the functions of lectins and the dynamics of glycolipids in living membranes. This review focuses on lectins binding to the glycosphingolipid globotriaosylceramide (Gb3), an attractive host cell receptor, particularly for pathogens and pathogenic products. Shiga toxin (Stx), from Shigella dysenteriae or Escherichia coli, which is one of the most virulent bacterial toxins, binds and clusters Gb3, leading to local negative membrane curvature and the formation of tubular plasma membrane invaginations as the initial step for clathrin-independent endocytosis. After internalization, it is embracing the retrograde transport pathway. In comparison, the homotetrameric lectin LecA from Pseudomonas aeruginosa can also bind to Gb3, triggering the so-called lipid zipper mechanism, which results in membrane engulfment of the bacterium as an important step for its cellular uptake. Notably, both lectins bind to Gb3 but induce distinct plasma membrane domains and exploit mainly different transport pathways. Not only, several other Gb3-binding lectins have been described from bacterial origins, such as the adhesins SadP (from Streptococcus suis) and PapG (from E. coli), but also from animal, fungal, or plant origins. The variety of amino acid sequences and folds demonstrates the structural versatilities of Gb3-binding lectins and asks the question of the evolution of specificity and carbohydrate recognition in different kingdoms of life.

• Shiga toxin
• bacterial adhesins
• carbohydrate
• globotriaosylceramide
• glycosphingolipid
• lectin
• valence

• ABO Blood-Group System/blood
• Blood Grouping and Crossmatching
• COVID-19/blood
• COVID-19/etiology
• COVID-19/transmission
• Humans
• Models, Biological
• Rh-Hr Blood-Group System/blood
• Risk Factors
• SARS-CoV-2/isolation & purification

• SARS-CoV-2
• lactoferrin
• molecular dynamics simulation
• shape complementarity
• sialic acid
• spike (S) glycoprotein

Lectins, and related receptors such as adhesins and toxins, are glycan-binding proteins from all origins that decipher the glycocode, i.e. the structural information encoded in the conformation of complex carbohydrates present on the surface of all cells. Lectins are still poorly classified and annotated, but since their functions are based on ligand recognition, their 3D-structures provide a solid foundation for characterization. UniLectin3D is a curated database that classifies lectins on origin and fold, with cross-links to literature, other databases in glycosciences and functional data such as known specificity. The database provides detailed information on lectins, their bound glycan ligands, and features their interactions using the Protein–Ligand Interaction Profiler (PLIP) server. Special care was devoted to the description of the bound glycan ligands with the use of simple graphical representation and numerical format for cross-linking to other databases in glycoscience. We conceived the design of the database architecture and the navigation tools to account for all organisms, as well as to search for oligosaccharide epitopes complexed within specified binding sites. UniLectin3D is accessible at https://www.unilectin.eu/unilectin3D.

Galactofuranose is a rare form of the well-known galactose sugar, and its occurrence in numerous pathogenic micro-organisms makes the enzymes responsible for its biosynthesis interesting targets. Herein, we review the role of these carbohydrate-related proteins with a special emphasis on the galactofuranosidases we recently characterized as an efficient recombinant biocatalyst.

• carbohydrate-based therapeutics
• galactofuranoside hydrolase
• galactofuranosyl transferase
• glycobiology
• pathogen diagnostics

• Carbohydrate Metabolism
• Carbohydrates/genetics
• Galactose/biosynthesis
• Galactose/genetics
• Galactose/metabolism
• Humans
• Hydrolases/genetics
• Mannans/metabolism
• Sugars/metabolism
• Transferases/genetics

• ABO Blood-Group System
• Angiotensin-Converting Enzyme 2
• Betacoronavirus
• COVID-19
• Coronavirus Infections/immunology
• Coronavirus Infections/transmission
• Glycosylation
• Humans
• Immunity, Innate
• Pandemics
• Peptidyl-Dipeptidase A
• Pneumonia, Viral/immunology
• Pneumonia, Viral/transmission
• Polysaccharides/immunology
• SARS-CoV-2
• Spike Glycoprotein, Coronavirus/immunology

• carbohydrate antigen
• gene duplication
• metagenome
• phylogeny
• symbiosis

• Animal microbiome
• Evolution
• Holobiont
• Metaorganism
• Phylosymbiosis

• Animals
• Bacteria/classification
• Bacteria/genetics
• Databases, Genetic
• High-Throughput Nucleotide Sequencing/methods
• Humans
• Metagenome/genetics
• Metagenome/physiology
• Microbiota/genetics
• Microbiota/physiology
• Phylogeny
• RNA, Ribosomal, 16S/genetics

• Deutsche Forschungsgemeinschaft
• Max-Planck-Gesellschaft

The use of immunodeficient mice transplanted with human hematopoietic stem cells is an accepted approach to study human-specific infectious diseases such as HIV-1 and to investigate multiple aspects of human immune system development. However, mouse and human are different in sialylation patterns of proteins due to evolutionary mutations of the CMP-N-acetylneuraminic acid hydroxylase (CMAH) gene that prevent formation of N-glycolylneuraminic acid from N-acetylneuraminic acid. How changes in the mouse glycoproteins’ chemistry affect phenotype and function of transplanted human hematopoietic stem cells and mature human immune cells in the course of HIV-1 infection are not known.

We mutated mouse CMAH in the NOD/scid-IL2Rγ_c^−/− (NSG) mouse strain, which is widely used for the transplantation of human cells, using the CRISPR/Cas9 system. The new strain provides a better environment for human immune cells. Transplantation of human hematopoietic stem cells leads to broad B cells repertoire, higher sensitivity to HIV-1 infection, and enhanced proliferation of transplanted peripheral blood lymphocytes. The mice showed no effect on the clearance of human immunoglobulins and enhanced transduction efficiency of recombinant adeno-associated viral vector rAAV2/DJ8.

NSG-cmah^−/− mice expand the mouse models suitable for human cells transplantation, and this new model has advantages in generating a human B cell repertoire. This strain is suitable to study different aspects of the human immune system development, provide advantages in patient-derived tissue and cell transplantation, and could allow studies of viral vectors and infectious agents that are sensitive to human-like sialylation of mouse glycoproteins.

The online version of this article (10.1186/s12865-018-0279-3) contains supplementary material, which is available to authorized users.

• CMP-N-acetylneuraminic acid hydroxylase
• HIV-1
• Hematopoietic stem cells
• NOD/scid-IL2Rγc −/− mice

The carbohydrate Galα1-3Galβ1-(3)4GlcNAc-R (α-Gal) is produced in all mammals except for humans, apes and old world monkeys that lost the ability to synthetize this carbohydrate. Therefore, humans can produce high antibody titers against α-Gal. Anti-α-Gal IgE antibodies have been associated with tick-induced allergy (i.e. α-Gal syndrome) and anti-α-Gal IgG/IgM antibodies may be involved in protection against malaria, leishmaniasis and Chagas disease. The α-Gal on tick salivary proteins plays an important role in the etiology of the α-Gal syndrome. However, whether ticks are able to produce endogenous α-Gal remains currently unknown. In this study, the Ixodes scapularis genome was searched for galactosyltransferases and three genes were identified as potentially involved in the synthesis of α-Gal. Heterologous gene expression in α-Gal-negative cells and gene knockdown in ticks confirmed that these genes were involved in α-Gal synthesis and are essential for tick feeding. Furthermore, these genes were shown to play an important role in tick-pathogen interactions. Results suggested that tick cells increased α-Gal levels in response to Anaplasma phagocytophilum infection to control bacterial infection. These results provided the molecular basis of endogenous α-Gal production in ticks and suggested that tick galactosyltransferases are involved in vector development, tick-pathogen interactions and possibly the etiology of α-Gal syndrome in humans.

• Evolution
• Glycans
• Glycobiology
• Host defense
• Microbial adhesins
• Microbiology
• Mucins
• Oral biology
• Saliva
• Salivary proteins

• Adaptive Immunity/immunology
• Animals
• Glycoproteins/immunology
• Humans
• Immunity, Innate/immunology
• Microbiota/immunology
• Mouth/immunology
• Mouth/microbiology
• Polysaccharides/immunology
• Saliva/immunology
• Saliva/microbiology

• R21 DE025826 NIDCR NIH HHS
• U01 CA221244 NCI NIH HHS
• T32 DE023526 NIDCR NIH HHS
• F32 DE028178 NIDCR NIH HHS
• R01 DE019807 NIDCR NIH HHS

• gastrointestinal
• glycan
• glycocode
• glycoprotein
• glycosylation
• microbiota
• mucin
• mucosal
• mucus

• Wellcome Trust
• B19303 Biotechnology and Biological Sciences Research Council

Naturally-acquired antibody responses to malaria parasites are not only directed to protein antigens but also to carbohydrates on the surface of Plasmodium protozoa. Immunoglobulin M responses to α-galactose (α-Gal) (Galα1-3Galβ1-4GlcNAc-R)-containing glycoconjugates have been associated with protection from P. falciparum infection and, as a result, these molecules are under consideration as vaccine targets; however there are limited field studies in endemic populations. We assessed a wide breadth of isotype and subclass antibody response to α-Gal in children from Mozambique (South East Africa) and Ghana (West Africa) by quantitative suspension array technology. We showed that anti-α-Gal IgM, IgG and IgG_1–4 levels vary mainly depending on the age of the child, and also differ in magnitude in the two sites. At an individual level, the intensity of malaria exposure to P. falciparum and maternally-transferred antibodies affected the magnitude of α-Gal responses. There was evidence for a possible protective role of anti-α-Gal IgG3 and IgG4 antibodies. However, the most consistent findings were that the magnitude of IgM responses to α-Gal was associated with protection against clinical malaria over a one-year follow up period, especially in the first months of life, while IgG levels correlated with malaria risk.

Self-nonself discrimination is a common theme for all of the organisms in different evolutionary branches, which is also the most fundamental step for host immune protection. Plenty of pattern recognition receptors (PRRs) with great diversity have been identified from different organisms to recognize various pathogen-associated molecular patterns (PAMPs) in the last two decades, depicting a complicated scene of host-pathogen interaction. However, the detailed mechanism of the complicate PAMPs–PRRs interactions at the contacting interface between pathogens and hosts is still not well understood. All of the cells are coated by glycosylation complex and thick carbohydrates layer. The different polysaccharides in extracellular matrix of pathogen-host are important for nonself recognition of most organisms. Coincidentally, massive expansion of PRRs, majority of which contain recognition domains of Ig, leucine-rich repeat (LRR), C-type lectin (CTL), C1q and scavenger receptor (SR), have been annotated and identified in invertebrates by screening the available genomic sequence. The phylum Mollusca is one of the largest groups in the animal kingdom with abundant biodiversity providing plenty of solutions about pathogen recognition and immune protection, which might offer a suitable model to figure out the common rules of immune recognition mechanism. The present review summarizes the diverse PRRs and common elements of various PAMPs, especially focusing on the structural and functional characteristics of canonical carbohydrate recognition proteins and some novel proteins functioning in molluscan immune defense system, with the objective to provide new ideas about the immune recognition mechanisms.

• carbohydrate complex
• immune recognition
• innate immunity
• molluscs
• pattern recognition receptor

• Amino Acid Sequence
• Computational Biology
• Eukaryota/metabolism
• N-Acetylneuraminic Acid/metabolism
• Phylogeny
• Protein Processing, Post-Translational

Pathogens infect hosts often through initial binding of their cell surface lectins to glycans expressed on the exterior of host cells. Thus, methods to evaluate the glycan-binding properties of pathogens are of great importance. Because of the multivalent nature of interactions of pathogens with glycans, the ability to assess the glycan density-dependent binding of pathogens is particularly important. In this study, we developed a facile technique to construct multivalent carbohydrate microarrays through immobilization of unmodified glycans on multivalent hydrazide-derivatized glass surfaces. This immobilization strategy does not require the use of multivalent glycoconjugates, which are typically prepared by using multistep sequences. The results of analysis of microarray images, obtained after incubation of multivalent glycan microarrays with cholera toxin B and pathogens such as uropathogenic E. coli and H. pylori, show that the binding affinities of toxins and pathogens for glycans are highly glycan density-dependent. Specifically, toxins and pathogens bind to glycans more strongly as the valency of the glycans on the microarrays is increased from 1 to 4. It is anticipated that the newly developed immobilization method will be applicable to the preparation of multivalent carbohydrate microarrays that are employed to evaluate multivalent glycan binding properties of a variety of pathogens and toxins.

Microarrays constructed by immobilizing free glycans on multivalent hydrazide-coated surfaces were applied to evaluate multivalent glycan binding properties of pathogens.

• Blood Group Antigens
• Female
• Fucose
• Fucosyltransferases/physiology
• Gastrointestinal Microbiome
• Humans
• Infant
• Infant, Newborn
• Milk, Human/chemistry
• Milk, Human/microbiology
• Galactoside 2-alpha-L-fucosyltransferase

• Allergen
• Basophil activation test (BAT)
• Bet v 1 homolog
• Fragaria vesca cv. Yellow Wonder
• Fragaria×ananassa
• Strawberry

• Allergens/genetics
• Allergens/immunology
• Antigens, Plant/genetics
• Antigens, Plant/immunology
• Basophils/immunology
• Cells, Cultured
• Food Hypersensitivity/immunology
• Food Hypersensitivity/prevention & control
• Fragaria/classification
• Fragaria/genetics
• Fragaria/immunology
• Fruit
• Genotype
• Humans

• carbohydrate
• leishmaniasis
• malaria
• toxoplasmosis
• vaccine

• Adjuvants, Immunologic
• Animals
• Antigens, Protozoan/immunology
• Bacterial Vaccines
• Carbohydrates/immunology
• Glycosylphosphatidylinositols/immunology
• Host-Parasite Interactions/immunology
• Humans
• Leishmania/immunology
• Leishmaniasis/immunology
• Leishmaniasis/prevention & control
• Malaria/immunology
• Malaria/prevention & control
• Malaria Vaccines
• Parasites/immunology
• Parasitic Diseases/immunology
• Parasitic Diseases/prevention & control
• Plasmodium/immunology
• Protozoan Vaccines/immunology
• Toxoplasma/immunology
• Toxoplasmosis/immunology
• Toxoplasmosis/prevention & control
• Vaccination

Human milk is the recommended and sole nutrient source for newborns. One of the largest components of human milk is oligosaccharides (HMOs) with major constituents determined by the mother genotype for the fucosyltransferase 2 (FUT2, secretor) gene. HMO variation has been related with infant microbiota establishment, diarrhea incidence, morbidity and mortality, IgE associated eczema and body composition.

We investigated the (i) dependence of several major representative HMOs on the FUT2 status assessed through breast milk 2’Fucosyllactose (2’FL) and (ii) the relation of the 2’FL status with infant growth up to 4 months of life.

From an open observatory, single center, longitudinal cohort study with quantitative human milk collection at 30, 60, and 120 days postpartum from 50 mothers, who gave birth to 25 female and 25 male singleton infants, we collected a representative sample of human milk. We quantified the following 5 representative HMOs: 2’FL, Lacto-N-tetraose (LNT), Lacto-N-neotetraose (LNnT), 3’Sialyllactose (3’SL) and 6’Sialyllactose (6’SL). We grouped the milk samples and corresponding infants according to the measured milk 2’FL concentrations at 30 days of lactation, which clustered around low concentrations (95% CI of mean 12–42 mg/L) and high concentrations (95% CI of mean 1880–2460 mg/L) with the former likely representing Secretor negative mothers. Infant anthropometric measures were recorded at birth, 1, 2 and 4 months of age. Relations among the quantified HMOs and the relation of the high and low 2’FL HMOs groups with infant growth parameters were investigated via linear mixed models.

The milk samples with low 2’FL concentration had higher LNT and lower LNnT concentrations compared to the samples with high 2’FL. The milk 3’- and 6’SL concentrations were independent of 2’FL. Over lactation time we observed a drop in the concentration of 2’FL, LNT, LNnT and 6’SL, especially from 1 to 2 months, while 3’SL remained at relatively constant concentration from 1 month onwards. Up to 4 months of age, we did not observe significant differences in body weight, body length, body mass index and head circumference of the infants who consumed breast milk with low or high FUT2 associated HMO concentrations and composition.

Our findings on HMO concentrations over time of lactation and clusters based on 2’FL concentrations confirm previous observations and suggest that LNnT and LNT are ‘co-regulated’ with the FUT2 dependent 2’FL concentration, with LNnT showing a positive and LNT a negative relation. Further, our findings also suggest that the relatively substantial variation in HMOs between the high and low 2’FL clusters do not impact infant growth of either sex up to 4 months of age. The study was registered in www.ClinicalTrial.gov (NCT01805011).

• Adult
• Breast Feeding
• Child Development/physiology
• Female
• Humans
• Infant
• Infant, Newborn
• Lactation/metabolism
• Longitudinal Studies
• Male
• Milk, Human/chemistry
• Milk, Human/metabolism
• Mothers
• Oligosaccharides/analysis
• Oligosaccharides/metabolism
• Young Adult

• biological roles
• evolution
• glycans

• Animals
• Evolution, Molecular
• Glycosylation
• Humans
• Lipids/genetics
• Nucleic Acids/genetics
• Polysaccharides/chemistry
• Polysaccharides/genetics
• Polysaccharides/metabolism
• Proteins/genetics

• P01 HL107150 NHLBI NIH HHS
• R01 GM032373 NIGMS NIH HHS
• U01 CA199792 NCI NIH HHS

• Neu5Gc
• anti-Gal
• anti-Neu5Gc
• natural anti-carbohydrate antibodies
• primate evolution
• virus carbohydrates.
• α-gal epitope

Complex glycans cover the gut epithelial surface to protect the cell from the environment. Invasive pathogens must breach the glycan layer before initiating infection. While glycan degradation is crucial for infection, this process is inadequately understood. Salmonella contains 47 glycosyl hydrolases (GHs) that may degrade the glycan. We hypothesized that keystone genes from the entire GH complement of Salmonella are required to degrade glycans to change infection. This study determined that GHs recognize the terminal monosaccharides (N-acetylneuraminic acid (Neu5Ac), galactose, mannose, and fucose) and significantly (p < 0.05) alter infection. During infection, Salmonella used its two GHs sialidase nanH and amylase malS for internalization by targeting different glycan structures. The host glycans were altered during Salmonella association via the induction of N-glycan biosynthesis pathways leading to modification of host glycans by increasing fucosylation and mannose content, while decreasing sialylation. Gene expression analysis indicated that the host cell responded by regulating more than 50 genes resulting in remodeled glycans in response to Salmonella treatment. This study established the glycan structures on colonic epithelial cells, determined that Salmonella required two keystone GHs for internalization, and left remodeled host glycans as a result of infection. These data indicate that microbial GHs are undiscovered virulence factors.

• Cellular ecology
• Glycans
• Glycoconjugates
• Natural variation
• Polymorphism

This mini review highlights several interesting aspects of glycan-mediated interactions that are common between cells, bacteria, and viruses. Glycans are ubiquitously found on all living cells, and in the extracellular milieu of multicellular organisms. They are known to mediate initial binding and recognition events of both immune cells and pathogens with their target cells or tissues. The host target tissues are hidden under a layer of secreted glycosylated decoy targets. In addition, pathogens can utilize and display host glycans to prevent identification as foreign by the host’s immune system (molecular mimicry). Both the host and pathogens continually evolve. The host evolves to prevent infection and the pathogens evolve to evade host defenses. Many pathogens express both glycan-binding proteins and glycosidases. Interestingly, these proteins are often located at the tip of elongated protrusions in bacteria, or in the leading edge of the cell. Glycan-protein interactions have low affinity and, as a result, multivalent interactions are often required to achieve biologically relevant binding. These enable dynamic forms of adhesion mechanisms, reviewed here, and include rolling (cells), stick and roll (bacteria) or surfacing (viruses).

• FimH
• cumulus oophorus
• glycans
• hyaluronan
• influenza A
• leukocytes
• mucus
• rolling adhesion
• sialic acids
• sperm
• stick and roll
• surfacing

• Animals
• Bacteria/pathogenicity
• Bacterial Physiological Phenomena
• Host-Pathogen Interactions
• Humans
• Polysaccharides/metabolism
• Proteins/metabolism
• Virus Physiological Phenomena
• Viruses/pathogenicity

The breadth and magnitude of P. falciparum-specific IgM and IgG responses are greater in the malaria-resistant Fulani versus the malaria-susceptible Dogon, and P. falciparum-specific IgM responses more strongly distinguish the two ethnic groups.

Background. People of the Fulani ethnic group are more resistant to malaria compared with genetically distinct ethnic groups, such as the Dogon people, in West Africa, and studies suggest that this resistance is mediated by enhanced antibody responses to Plasmodium falciparum antigens. However, prior studies measured antibody responses to <0.1% of P falciparum proteins, so whether the Fulani mount an enhanced and broadly reactive immunoglobulin (Ig)M and IgG response to P falciparum remains unknown. In general, little is known about the extent to which host genetics influence the overall antigen specificity of IgM and IgG responses to natural infections.

Methods. In a cross-sectional study in Mali, we collected plasma from asymptomatic, age-matched Fulani (n = 24) and Dogon (n = 22) adults with or without concurrent P falciparum infection. We probed plasma against a protein microarray containing 1087 P falciparum antigens and compared IgM and IgG profiles by ethnicity.

Results. We found that the breadth and magnitude of P falciparum-specific IgM and IgG responses were significantly higher in the malaria-resistant Fulani versus the malaria-susceptible Dogon, and, unexpectedly, P falciparum-specific IgM responses more strongly distinguished the 2 ethnic groups.

Conclusions. These findings point to an underappreciated role for IgM in protection from malaria, and they suggest that host genetics may influence the antigen specificity of IgM and IgG responses to infection.

• Dogon
• Fulani
• Plasmodium falciparum
• antibodies
• malaria

• Amino Acid Sequence
• Animals
• Carbohydrate Sequence
• Crystallography, X-Ray
• Cytokines/chemistry
• Cytokines/genetics
• Cytokines/metabolism
• Epitopes/chemistry
• Epitopes/metabolism
• GPI-Linked Proteins/chemistry
• GPI-Linked Proteins/genetics
• GPI-Linked Proteins/metabolism
• HEK293 Cells
• Humans
• Lectins/chemistry
• Lectins/genetics
• Lectins/metabolism
• Ligands
• Lipopolysaccharides/chemistry
• Lipopolysaccharides/metabolism
• Mice
• Models, Chemical
• Models, Molecular
• Molecular Sequence Data
• Molecular Structure
• Monosaccharides/chemistry
• Monosaccharides/metabolism
• Polysaccharides/chemistry
• Polysaccharides/metabolism
• Protein Binding
• Protein Structure, Tertiary
• Sequence Homology, Amino Acid
• Streptococcus pneumoniae/chemistry
• Streptococcus pneumoniae/metabolism
• Surface Plasmon Resonance

• S10 RR024715 NCRR NIH HHS
• R01 AI063596 NIAID NIH HHS
• GM98791 NIGMS NIH HHS
• R01 GM055984 NIGMS NIH HHS
• P41 GM103694 NIGMS NIH HHS
• S10 RR008389 NCRR NIH HHS
• 1S10RR024715 NCRR NIH HHS
• GM062116 NIGMS NIH HHS
• R24 GM098791 NIGMS NIH HHS
• T32 GM008505 NIGMS NIH HHS
• S10 RR013790 NCRR NIH HHS
• S10 RR13790 NCRR NIH HHS
• R01 AI055258 NIAID NIH HHS
• P30 CA014520 NCI NIH HHS
• R01GM55984 NIGMS NIH HHS
• U54 GM062116 NIGMS NIH HHS
• R01AI063596 NIAID NIH HHS