The genetics of capsule and lipooligosaccharide biosynthesis in haemophilus influenzae

Haemophilus influenzae is a Gram-negative bacterium that is a commensal of the human nasopharynx. On occasion, the balance between colonization and asymptomatic carriage breaks down and disease occurs. ⁸¹ Disease caused by H. influenzae is significantly affected by the capsulation state of the organism (see below). Both nontypable H. influenzae, which does not express a capsule, and H. influenzae type b are a significant cause of upper respiratory tract infections. ^81,84 Systemic disease caused by H. influenzae, the most serious manifestation of which involves crossing the blood-brain barrier leading to meningitis, is caused predominantly by type b organisms, ⁸¹ and occurs primarily in neonates and infants during the time after maternal antibody protection is lost and before the developing immune system is capable of protecting the infant. ¹³ Recently, implementation of vaccines effective against type b H. influenzae has dramatically reduced the number of invasive disease episodes in vaccinated populations. ^{47,51,58,77,78} Haemophilus influenzae is capable of expressing two major surface polysaccharides. These are capsule and lipooligosaccharide (LOS). Capsule is a polymeric carbohydrate structure that forms the outermost layer of the bacterium. LOS contains both lipid and carbohydrate and is the major component of the outer leaflet of the outer membrane of H. influenzae. Both capsule and LOS have been shown to be important contributors to H. influenzae ‘s ability to colonize and infect the human host. In this chapter we attempt to highlight the impact that genetic research into the biosynthesis of these two structures has made on understanding the pathogenesis of H. influenzae.