Pseudomonas aeruginosa lipopolysaccharide: A major virulence factor, initiator of inflammation and target for effective immunity

Abstract

Pseudomonas aeruginosa is one of the most important bacterial pathogens encountered by immunocompromised hosts and patients with cystic fibrosis (CF), and the lipopolysaccharide (LPS) elaborated by this organism is a key factor in virulence and both innate and acquired host responses to infection. The molecule has a fair degree of heterogeneity in its lipid A and O-antigen structure, and elaborates 2 different outer-core glycoforms, of which only one binds O-antigen. A close relatedness between the chemical structures and genes encoding biosynthetic enzymes has been established, with 11 major O-antigen groups identified. The lipid A can be variably penta-, hexa-or hepta-acylated, and these isoforms have differing potencies when activating host innate immunity via binding to Toll-like receptor 4. The O-antigen is a major target for protective immunity as evidenced by numerous animal studies, but attempts, to date, to produce a human vaccine targeting these epitopes have not been successful Newer strategies employing live attenuated P. aeruginosa, or heterologous attenuated bacteria expressing P. aeruginosa O-antigens are potential means to solve some of the existing problems related to making a P. aeruginosa LPS-specific vaccine. Overall, there is now a large amount of information available about the genes and enzymes needed to produce the P. aeruginosa LPS, detailed chemical structures have been determined for the major O-antigens, and significant biologic and immunologic studies have been conducted to define the role of this molecule in virulence and immunity to P. aeruginosa infection.

The Effect of Alkaloids, Saponinsand Thymoquinone of Nigella Sativa Seeds on Biofilm Production, Motility, Outer Membrane Proteins and Lipopolysaccharide of Some Bacteria.

“…It is also involved in the attachment to host cells and it is important for the virulence and pathogenesis of many bacterial species, including Pseudomonas aeruginosa, Salmonella species, and Escherichia coli (66)(67)(68).…”

Mechanisms of O-Antigen Structural Variation of Bacterial Lipopolysaccharide (LPS)

“…To date, it is not known precisely which signals in hosts with CF favour and allow for a predominance of mucoid strains compared to non-mucoid strains. In vitro studies, it has been demonstrated that both bacterial phenotypes exhibit similar behaviour and that successive passages in culture media inhibit the expression of the non-mucoid phenotype [4,5].…”

“…Nutrient gradients occur from the surface of the biofilm to the most internal parts, thereby influencing the bacterial physiology and consequently modifying the speed of growth, the generation time, the susceptibility to antibiotics (due to factors such as the presence of a diffusion barrier to antibiotics), the antigenic variability of individuals, the susceptibility to opsonisation and phagocytosis and even the alginate functions as a negative immunomodulator for the host [4].…”

Pseudomonas aeruginosa–Induced Apoptosis in Airway Epithelial Cells Is Mediated by Gap Junctional Communication in a JNK-Dependent Manner

“…Alterations in the integrity of the host epithelium during infection may cause life-threatening conditions. In cystic fibrosis (CF), chronic infection of the airways by Pseudomonas aeruginosa leads to severe pulmonary damage and is responsible for mortality and morbidity in the CF population (2). CF is a genetic disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene that codes for a cAMP-and ATP-regulated chloride channel that is located in glandular and surface airway epithelial cells.…”