Human Monoclonal Antibodies to Escherichia coli Outer Membrane Protein A Porin Domain Cause Aggregation but Do Not Alter In Vivo Bacterial Burdens in a Murine Sepsis Model.

Escherichia coli is one of the most frequent human pathogens, increasingly exhibits antimicrobial resistance, and has complex interactions with the host immune system. E. coli exposure or infection can result in the generation of antibodies specific for outer membrane protein A (OmpA), a multifunctional porin. We identified four OmpA-specific naturally occurring antibodies from healthy human donor B cells and assessed their interactions with E. coli and OmpA. These antibodies are highly specific for OmpA, exhibiting no cross-reactivity to a strain lacking ompA and retaining binding to both laboratory and clinical isolates of E. coli in enzyme-linked immunosorbent assay (ELISA) and immunofluorescence assays. One monoclonal antibody (Mab), designated ECOL-11, is specific for the extracellular N-terminal porin domain of OmpA and induces growth phase-specific bacterial aggregation. This aggregation is not induced by the fragment antigen binding (Fab) form of the MAb, suggesting the importance of bivalency for this aggregating activity. ECOL-11 decreases adhesion and phagocytosis of E. coli by RAW 264.7 macrophage-like cells, possibly by inhibiting the adhesion functions of OmpA. Despite this in vitro phenotype, organ E. coli burdens were not altered by antibody prophylaxis in a murine model of lethal E. coli septic shock. Our findings support the importance of OmpA at the host-pathogen interface and begin to explore the implications and utility of E. coli-specific antibodies in human hosts.

Quiz-Based Microlearning at Scale: a Rapid Educational Response to COVID-19.

Virtual quizzing is a viable model for continuing education at a large scale, particularly during the COVID-19 pandemic. By leveraging technology, microlearning encourages mobile education that is engaging, flexible, and accessible. Learners reported that this format was effective and preferable to traditional methods of education, suggesting further opportunity for innovation.