Assessment of the Glycan-Binding Profile ofPseudomonas aeruginosaPAO1

Abstract

ABSTRACTPseudomonas aeruginosais an opportunistic pathogen that can establish acute and chronic infections in individuals that lack fully functional innate immunity. In particular, phagocytosis by neutrophils and macrophages is a key mechanism that modulates host control and clearance ofP. aeruginosa. Individuals with neutropenia or cystic fibrosis are highly susceptible toP. aeruginosainfection thus underscoring the importance of the host innate immune response. Cell-to-cell contact between host innate immune cells and the pathogen, a first step in phagocytic uptake, is facilitated by simple and complex glycan structures present at the host cell surface. We have previously shown that endogenous polyanionic N-linked glycans localized to the cell surface of phagocytes mediate binding and subsequent phagocytosis ofP. aeruginosa. However, the suite of glycans thatP. aeruginosabinds to on host phagocytic cells remains poorly characterized. Here we demonstrate, with the use of exogenous N-linked glycans and a glycan array, thatP. aeruginosaPAO1 preferentially attaches to a subset of glycans, including a bias towards monosaccharide versus more complex glycan structures. Consistent with these findings, we were able to competitively inhibit bacterial adherence and uptake by the addition of exogenous N-linked mono- and di-saccharide glycans. We discuss of findings in the context of previous reports ofP. aeruginosaglycan binding.IMPORTANCEP. aeruginosabinds to a variety of glycans as part of its interaction with host cells, and a number ofP. aeruginosa-encoded receptors and target ligands have been described that allow this microbe to bind to such glycans. Here we extend this work by studying the glycans used byP. aeruginosaPAO1 to bind to phagocytic cells and by using a glycan array to characterize the suite of such molecules that could facilitate host cell-binding by this microbe. This study provides an increased understanding of the glycans bound byP. aeruginosa, and furthermore, provides a useful dataset for future studies ofP. aeruginosa-glycan interactions.