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One of the mechanisms contributing to the protection by breast-feeding of the newborn against enteric diseases is related to the ability of human milk oligosaccharides to prevent the attachment of pathogenic bacteria to the duodenual epithelium. Indeed, a variety of fucosylated oligosaccharides, specific to human milk, form part of the innate immune system. In the present study, we demonstrate the specific blocking of PA-IIL, a fucose-binding lectin of the human pathogen Pseudomonas aeruginosa, by milk oligosaccharides. Two fucosylated epitopes, Lewis a and 3-fucosyl-lactose (Lewis x glucose analogue) bind to the lectin with dissociation constants of 2.2x10(-7) M and 3.6x10(-7) M respectively. Thermodynamic studies indicate that these interactions are dominated by enthalpy. The entropy contribution is slightly favourable when binding to fucose and to the highest-affinity ligand, Lewis a. The high-resolution X-ray structures of two complexes of PA-IIL with milk oligosaccharides allow the precise determination of the conformation of a trisaccharide and a pentasaccharide. The different types of interaction between the oligosaccharides and the protein involve not only hydrogen bonding, but also calcium- and water-bridged contacts, allowing a rationalization of the thermodynamic data. This study provides important structural information about compounds that could be of general application in new therapeutic strategies against bacterial infections.

Background The Coronavirus disease 2019 (COVID‐19) pandemic is having a major global impact, and the resultant response in the development of new diagnostics is unprecedented. The detection of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has a role in managing the pandemic. We evaluated the feasibility of using SARS‐CoV‐2 peptide Kode Technology‐modified red cells (C19‐kodecytes) to develop an assay compatible with existing routine serologic platforms. Study Design and Methods A panel of eight unique red cells modified using Kode Technology function‐spacer‐lipid constructs and bearing short SARS‐CoV‐2 peptides was developed (C19‐kodecyte assay). Kodecytes were tested against undiluted expected antibody‐negative and ‐positive plasma samples in manual tube and three column agglutination technology (CAT) platforms. Parallel analysis with the same peptides in solid phase by enzyme immunoassays was performed. Evaluation samples included >120 expected negative blood donor samples and >140 COVID‐19 convalescent plasma samples, with independent serologic analysis from two centers. Results Specificity (negative reaction rate against expected negative samples) in three different CAT platforms against novel C19‐kodecytes was >91%, which correlated with published literature. Sensitivity (positive reaction rate against expected positive convalescent, PCR‐confirmed samples) ranged from 82% to 97% compared to 77% with the Abbott Architect SARS‐CoV‐2 IgG assay. Manual tube serology was less sensitive than CAT. Enzyme immunoassay results with some Kode Technology constructs also had high sensitivity. Conclusions C19‐kodecytes are viable for use as serologic reagent red cells for the detection of SARS‐CoV‐2 antibody with routine blood antibody screening equipment.

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