Lipooligosaccharide P-k (Gal alpha 1-4Gal beta 1-4Glc) epitope of Moraxella catarrhalis is a factor in resistance to bactericidal activity mediated by normal human serum

Moraxella catarrhalis is a respiratory pathogen responsible for acute bacte rial otitis media in children and exacerbation of chronic bronchitis in adu lts. M. catarrhalis strains are frequently resistant to the bactericidal ac tivity of normal human serum. In order to determine if the lipooligosacchar ide (LOS) of M. catarrhalis has a role in serum resistance, the UDP-glucose -4-epimerase (galE) gene was identified, cloned, and sequenced and a deleti on/insertion mutation was introduced into M. catarrhalis strain 2951. GalE enzymatic activity, measured in whole-cell lysates, was ablated in M. catar rhalis 2951 galE. Mass spectrometric analysis of LOS isolated with hot phen ol-water confirmed that strain 2951 produced a type A LOS. These studies sh owed that the LOS from 2951 galE had lost two hexose residues due to the ga lE mutation and that the resultant LOS structure lacked the (Gal alpha 1-4G al beta 1-4Glc) P-k epitope found on M. catarrhalis 2951. Wild-type M. cata rrhalis 2951 is resistant to complement-mediated serum bactericidal activit y. In contrast, a greater than 2-log(10)-unit reduction in CFU occurred aft er incubation of 2951 galE in either 50 or 25% pooled human serum (PNHS), a nd CFU in 10% PNHS decreased by about 1 log(10) unit. These studies suggest that the P-k epitope of the LOS may be an important factor in the resistan ce of M. catarrhalis to the complement-mediated bactericidal effect of norm al human serum.