Assessment of the Glycan-Binding Profile of Pseudomonas aeruginosa PAO1

Abstract

ABSTRACT Pseudomonas aeruginosa is an opportunistic pathogen that can establish acute and chronic infections in individuals who lack fully functional innate immunity. In particular, phagocytosis by neutrophils and macrophages is a key mechanism that modulates host control and clearance of P. aeruginosa. Individuals with neutropenia or cystic fibrosis are highly susceptible to P. aeruginosa infection, 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 the binding and subsequent phagocytosis of P. aeruginosa cells. However, the suite of glycans that P. aeruginosa cells bind to on host phagocytic cells remains poorly characterized. Here, we demonstrate, with the use of exogenous N-linked glycans and a glycan array, that P. aeruginosa PAO1 cells preferentially attach to a subset of glycans, including a bias toward 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 disaccharide glycans. We discuss our findings in the context of previous reports of P. aeruginosa glycan binding. IMPORTANCE P. aeruginosa cells bind to a variety of glycans as part of their interaction with host cells, and a number of P. 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 by P. aeruginosa PAO1 cells to bind to phagocytic cells and by using a glycan array to characterize the suite of such molecules that can facilitate host cell binding by this microbe. This study provides an increased understanding of the glycans bound by P. aeruginosa and furthermore provides a useful data set for future studies of P. aeruginosa-glycan interactions.

Keywords

• Pseudomonas aeruginosa
• glycan
• array
• phagocytosis
• host-pathogen interactions