Exopolysaccharides from Burkholderia cenocepacia Inhibit Neutrophil Chemotaxis and Scavenge Reactive Oxygen Species

Robert K. Ernst,Johan Bylund,Paola Cescutti,David P. Speert,Lee-Anna Burgess

doi:10.1074/jbc.m510692200

Robert K. Ernst, Johan Bylund + Show 3 more

Open Access

https://doi.org/10.1074/jbc.m510692200

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Abstract

Bacteria belonging to the Burkholderia cepacia complex are important opportunistic pathogens in compromised hosts, particularly patients with cystic fibrosis or chronic granulomatous disease. Isolates of B. cepacia complex may produce large amounts of exopolysaccharides (EPS) that endow the bacteria with a mucoid phenotype and appear to facilitate bacterial persistence during infection. We showed that EPS from a clinical B. cenocepacia isolate interfered with the function of human neutrophils in vitro; it inhibited chemotaxis and production of reactive oxygen species (ROS), both essential components of innate neutrophil-mediated host defenses. These inhibitory effects were not due to cytotoxicity or interference with intracellular calcium signaling. EPS also inhibited enzymatic generation of ROS in cell-free systems, indicating that it scavenges these bactericidal products. B. cenocepacia EPS is structurally distinct from Pseudomonas aeruginosa alginate, yet they share the capacity to scavenge ROS and inhibit chemotaxis. These properties could explain why the two bacterial species resist clearance from the infected cystic fibrosis lung.

Highlights

Bacteria belonging to the Burkholderia cepacia complex (BCC)3 comprise a family of at least nine different species, all of which are opportunistic pathogens in compromised human hosts
BCC are largely resistant to the action of antibacterial peptides/proteins [6], which may explain the virulence of BCC in chronic granulomatous disease (CGD) patients, the phagocytes of which rely solely on these non-oxidative means of microbial killing
B. cenocepacia EPS Inhibits Neutrophil Chemotaxis—We investigated whether B. cenocepacia EPS inhibits neutrophil chemotaxis in vitro as has been described for alginate from various P. aeruginosa strains [14]

Summary

Introduction

Bacteria belonging to the Burkholderia cepacia complex (BCC) comprise a family of at least nine different species, all of which are opportunistic pathogens in compromised human hosts. BCC species were initially described as plant pathogens [1], but all species have the ability to cause serious infections in patients with cystic fibrosis (CF) or chronic granulomatous disease (CGD) [2] These two disease conditions are quite disparate, CF being caused by dysfunctional chloride transport in the lung epithelium [3] and CGD being caused by an inability of phagocytes to generate the reactive oxygen species (ROS) important for microbial killing [4]. They may share features explaining the virulence of BCC in these particular patient groups. The most highly bactericidal ROS are formed when H2O2 reacts with myeloperoxidase, an enzyme located in the azurophilic granules of neutrophils, to form hypochlorous acid (HOCl, known as bleach), which is very toxic to almost all microbes [11]

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