DECORATION OF LIPOPOLYSACCHARIDE WITH PHOSPHORYLCHOLINE - A PHASE-VARIABLE CHARACTERISTIC OF HAEMOPHILUS-INFLUENZAE

Choline, although not a nutritional requirement for Haemophilus influe nzae, is taken up from the growth medium and incorporated into its lip opolysaccharide (LPS). Incorporated choline is in the form of phosphor ylcholine (ChoP) based on the reactivity with the monoclonal antibody with specificity for this structure, TEPC-15. Incorporation of [H-3]ch oline from the growth medium and expression of the TEPC-15 epitope und ergo high-frequency phase variation, characteristic of other LPS struc tures in this species. The expression and phase variation of ChoP requ ire a previously identified locus involved in LPS biosynthesis, lid. T he first gene in lid, licA, contains a translational switch based on v ariation in the number of intragenic tandem repeats of the sequence 5' -CAAT-3', The full-length LicA polypeptide resembles choline kinases o f eucaryotes, suggesting that the pathway for choline incorporation in to the H. influenzae glycolipid has similarities to the pathway for ch oline incorporation in eucaryotic lipid synthesis. The display of ChoP , a host-like structure, renders the organism more rather than less su sceptible to the bactericidal activity of human serum. The increased s erum sensitivity of variants with ChoP correlates with higher serum im munoglobulin G titers to LPS containing this structure. ChoP appears t o be a cell surface feature common to a number of pathogens of the hum an respiratory tract, including Streptococcus pneumoniae and mycoplasm as. In the case of H. influenzae, its primary contribution to pathogen esis does not appear to be antigenic variation to evade host humoral c learance mechanisms.