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 as well as 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 two different outer-core glycoforms, of which only one is ligated to the
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 (TLR4). 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.