Identification of cell-surface glycans that mediate motility-dependent binding and internalization of Pseudomonas aeruginosa by phagocytes

Sanchez, Hector; Hopkins, Daniel; Demirdjian, Sally; Gutierrez, Cecilia; O’Toole, George A.; Neelamegham, Sriram; Berwin, Brent

doi:10.1016/j.molimm.2020.12.012

Cited by 7 publications

(23 citation statements)

References 48 publications

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“…The binding of P. aeruginosa to glycans has been explored previously in several contexts. We showed that Nlinked glycans and glycosaminoglycans on phagocytes can mediate attachment and uptake of P. aeruginosa by macrophages (10). N-linked glycans have also been implicated as ligands for bacterial attachment to epithelial cells (18,19).…”

Section: Introductionmentioning

confidence: 90%

“…We previously demonstrated that if N-linked glycan synthesis is inhibited on host phagocytic cells the ability of P. aeruginosa to bind to the cell surface via these glycans is reduced (10). We hypothesized that the sugars that comprise N-linked glycan structures are necessary for binding and uptake of P. aeruginosa.…”

Section: Thp-1 Cellsmentioning

confidence: 99%

“…In this set of experiments, we utilized P. aeruginosa PAO1, a motile strain of bacteria previously shown to interact with cell surface glycans (10,30), and performed gentamicin protection assays with human THP-1 monocytic cell lines, as reported (4,5,9,10), to assess interaction of the microbe with host cells. The assays were performed for 45 minutes, which we have showed previously allows for a reproducible measure of bacterial attachment and subsequent phagocytosis, with minimal change in viability of the internalized bacteria (4,5,9,10).…”

Section: Thp-1 Cellsmentioning

confidence: 99%

“…These studies, which suggested that P. aeruginosa binds to clustered polyanions, guided our previous work that revealed that endogenous negatively charged glycosaminoglycans (GAGs) can mediate P. aeruginosa adhesion. In turn, this observation led to the conclusion that N-linked glycans on phagocytes play a role in bacterial binding and phagocytosis (10). Therefore, a central goal of this study is to further elucidate the initial carbohydrate "handshake" between phagocytic cells and P. aeruginosa.…”

Section: Introductionmentioning

confidence: 97%

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Assessment of the Glycan-Binding Profile ofPseudomonas aeruginosaPAO1

Sanchez

O’Toole

Berwin

2023

Preprint

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Pseudomonas 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.

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Section: Introductionmentioning

confidence: 90%

Section: Thp-1 Cellsmentioning

confidence: 99%

Section: Thp-1 Cellsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

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Assessment of the Glycan-Binding Profile ofPseudomonas aeruginosaPAO1

Sanchez

O’Toole

Berwin

2023

Preprint

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“…Adherence of microbial pathogens to the host cells and matrix is an important aspect of virulence, as it mediates colonisation and infection [ 55 ]. In addition, adherence to host phagocytic cell surface HS can be a precursor to the phagocytosis of bacteria [ 56 ]. Treatment with exogenous heparin or its mimetics may be proposed based on a decoy mechanism, reducing direct microbe interaction with cell surface HS by competition.…”

Section: Non-anticoagulant Action Of Heparin and Sepsismentioning

confidence: 99%

Heparin, Heparan Sulphate and Sepsis: Potential New Options for Treatment

Hogwood

Gray

2023

Pharmaceuticals

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Sepsis is a life-threatening hyperreaction to infection in which excessive inflammatory and immune responses cause damage to host tissues and organs. The glycosaminoglycan heparan sulphate (HS) is a major component of the cell surface glycocalyx. Cell surface HS modulates several of the mechanisms involved in sepsis such as pathogen interactions with the host cell and neutrophil recruitment and is a target for the pro-inflammatory enzyme heparanase. Heparin, a close structural relative of HS, is used in medicine as a powerful anticoagulant and antithrombotic. Many studies have shown that heparin can influence the course of sepsis-related processes as a result of its structural similarity to HS, including its strong negative charge. The anticoagulant activity of heparin, however, limits its potential in treatment of inflammatory conditions by introducing the risk of bleeding and other adverse side-effects. As the anticoagulant potency of heparin is largely determined by a single well-defined structural feature, it has been possible to develop heparin derivatives and mimetic compounds with reduced anticoagulant activity. Such heparin mimetics may have potential for use as therapeutic agents in the context of sepsis.

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Harnessing aptamers for the biosensing of cell surface glycans – A review

Liu,

Zhao,

et al. 2024

Analytica Chimica Acta

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Identification of cell-surface glycans that mediate motility-dependent binding and internalization of Pseudomonas aeruginosa by phagocytes

Cited by 7 publications

References 48 publications

Assessment of the Glycan-Binding Profile ofPseudomonas aeruginosaPAO1

Assessment of the Glycan-Binding Profile ofPseudomonas aeruginosaPAO1

Heparin, Heparan Sulphate and Sepsis: Potential New Options for Treatment

Harnessing aptamers for the biosensing of cell surface glycans – A review

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