Decoration of lipopolysaccharide with phosphorylcholine: a phase-variable characteristic of Haemophilus influenzae

Abstract

Choline, although not a nutritional requirement for Haemophilus influenzae, is taken up from the growth medium and incorporated into its lipopolysaccharide (LPS). Incorporated choline is in the form of phosphorylcholine (ChoP) based on the reactivity with the monoclonal antibody with specificity for this structure, TEPC-15. Incorporation of [3H]choline from the growth medium and expression of the TEPC-15 epitope undergo high-frequency phase variation, characteristic of other LPS structures in this species. The expression and phase variation of ChoP require a previously identified locus involved in LPS biosynthesis, lic1. The first gene in lic1, licA, contains a translational switch based on variation in the number of intragenic tandem repeats of the sequence 5'-CAAT-3'. The full-length LicA polypeptide resembles choline kinases of eucaryotes, suggesting that the pathway for choline incorporation into the H. influenzae glycolipid has similarities to the pathway for choline incorporation in eucaryotic lipid synthesis. The display of ChoP, a host-like structure, renders the organism more rather than less susceptible to the bactericidal activity of human serum. The increased serum sensitivity of variants with ChoP correlates with higher serum immunoglobulin G titers to LPS containing this structure. ChoP appears to be a cell surface feature common to a number of pathogens of the human respiratory tract, including Streptococcus pneumoniae and mycoplasmas. In the case of H. influenzae, its primary contribution to pathogenesis does not appear to be antigenic variation to evade host humoral clearance mechanisms.