Regulation of lipopolysaccharide O antigen expression in Pseudomonas aeruginosa

Abstract

Pseudomonas aeruginosa is a Gram-negative bacterium that is ubiquitously found in the environment. It is an important opportunistic pathogen in immunocompromised patients and causes life-threatening lung infections in individuals with cystic fibrosis. A prominent virulence factor for many Gram-negative bacteria, including P. aeruginosa, is lipopolysaccharide (LPS), which is an immunodominant antigen located in the outer portion of the outer membrane. P. aeruginosa produces two O antigens that are attached to lipid A + core: a B-band O antigen and an A-band O polysaccharide. The B-band O antigen-repeating unit of LPS is responsible for serotype specificity; strains lacking O antigen have been shown to be less virulent in animal models of infection. What is less well understood is how the O antigen chain length is regulated and why P. aeruginosa and some other bacteria show two preferred O antigen lengths. P. aeruginosa encodes two genes encoding O antigen chain length regulators. These genes, wzz1 and wzz2, influence the expression of the long and very long chain lengths, respectively. The long chain length appears more important for resistance to the action of sera and virulence in a mouse model of infection, while the very long chain length appears to be more sensitive to environmental stress conditions. Studies in other bacteria point to regulation at the level of transcription and complex formation as being involved in determining the O antigen chain length and may provide clues to the regulation in P. aeruginosa.