Alginate synthesis by Pseudomonas aeruginosa: a key pathogenic factor in chronic pulmonary infections of cystic fibrosis patients

Abstract

Pulmonary infection by mucoid, alginate-producing Pseudomonas aeruginosa is the leading cause of mortality among patients suffering from cystic fibrosis. Alginate-producing P. aeruginosa is uniquely associated with the environment of the cystic fibrosis-affected lung, where alginate is believed to increase resistance to both the host immune system and antibiotic therapy. Recent evidence indicates that P. aeruginosa is most resistant to antibiotics when the infecting cells are present as a biofilm, as they appear to be in the lungs of cystic fibrosis patients. Inhibition of the protective alginate barrier with nontoxic compounds targeted against alginate biosynthetic and regulatory proteins may prove useful in eradicating P. aeruginosa from this environment. Our research has dealt with elucidating the biosynthetic pathway and regulatory mechanism(s) responsible for alginate synthesis by P. aeruginosa. This review summarizes reports on the role of alginate in cystic fibrosis-associated pulmonary infections caused by P. aeruginosa and provides details about the biosynthesis and regulation of this exopolysaccharide.

Involvement of Toll-like Receptor (TLR) 2 and TLR4 in Cell Activation by Mannuronic Acid Polymers

“…Human embryonic kidney (HEK) 293 cells (ATCC) were grown in Dulbecco's modified Eagle's medium (Invitrogen) with 0.01% L-glutamine, 40 g/ml gentamycin, (referred to as DMEM) and 10% heatinactivated FCS (HyClone) at 37°C and 8% CO 2 .…”

“…Furthermore, poly-M protects mice from lethal x-irradiation and bacterial infections without imparting toxicity (6). 2 Thus, a possible exploitation of poly-M could be as a general immunostimulator for protection against disease. FIG.…”

“…marine brown seaweed but also as an exopolysaccharide produced by bacteria, like the opportunistic pathogen Pseudomonas aeruginosa that colonizes patients with cystic fibrosis (2) and may cause severe infections in critically ill patients.…”

Chronic pulmonary pseudomonal infection in patients with cystic fibrosis: A model for early phase symbiotic evolution

“…Chronic infections due to bacterial persistence in the form of biofilm have gained recognition over the last two decades (Hoiby et al, 2001(Hoiby et al, , 2010May et al, 1991). The theory of pseudomonal biofilm assembly on the mucosal surface of CF airway has begun to address bacterial lifestyle changes that include differential gene expression, isogenic divergence, and organized cell-to-cell communication (Boucher, 2004;Mowat et al, 2011;Oliver, 2010;Oliver & Mena, 2010;Whiteley et al, 2001;Wu et al, 2001).…”

Functional metagenomic characterization of antibiotic resistance genes in agricultural soils from China

“…DCGen3002-1 encoded a protein similar to phosphomannomutase and DCKan30A29 encoded a protein similar to nucleotide sugar dehydrogenase, both of which are responsible for alginate polymerization and the resultant alginate layer would cause a mucoid phenotype and provide a protective barrier against host immune defenses and antibiotics (May et al, 1991;Naught et al, 2002). DCKan30A03 encoded 2-oxoglutarate dehydrogenase is involved in glutamine utilization and could reduce cell wall hydrophobicity, which has previously been reported to be important for multiple antibiotic resistance (Wolff et al, 2009).…”