Antigenic drift of non-encapsulated Haemophilus influenzae major outer membrane protein P2 in patients with chronic bronchitis is caused by point mutations.
The sequence of the gene encoding major outer membrane protein (MOMP) P2 of antigenic variants of non-encapsulated Haemophilus influenzae isolated from persistently infected chronic bronchitis patients was analysed. Antigenic drift was shown to result from single base changes in the P2 gene, all generating amino acid changes in the surface-exposed loops of MOMP P2, predominantly in loop 6. Similar single base changes were observed in H. influenzae persistently present in a subcutaneous cage implanted in rabbits, as well as in a spontaneous H. influenzae mutant that had survived MOMP P2 specific monoclonal-antibody-dependent bactericidal killing in vitro. We hypothesize that accumulation of point mutations under the selection pressure of immunity is a mechanism of antigenic drift of a surface-exposed protein during persistent H. influenzae infection.
Duim
B
B
Department of Medical Microbiology, Academic Medical Centre, Amsterdam, The Netherlands.
van Alphen
L
L
Eijk
P
P
Jansen
H M
HM
Dankert
J
J
D000595:Amino Acid Sequence; D000818:Animals; D000940:Antigenic Variation / Q000235:genetics*; D000942:Antigens, Bacterial / Q000235:genetics; D016667:Bacterial Capsules; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics* / Q000276:immunology; D001483:Base Sequence; D001991:Bronchitis / Q000382:microbiology*; D002908:Chronic Disease; D015194:Diffusion Chambers, Culture; D004195:Disease Models, Animal; D005787:Gene Frequency; D005798:Genes, Bacterial / Q000235:genetics; D006193:Haemophilus influenzae / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008969:Molecular Sequence Data; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011817:Rabbits; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D013997:Time Factors
D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; C074703:outer membrane protein P2, Haemophilus influenzae type b