Antigenic drift of non-encapsulated Haemophilus influenzae major outer membrane protein P2 in patients with chronic bronchitis is caused by point mutations |
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| Authors: | Birgitta Duim Loek van Alphen Paul Eijk Henk M. Jansen Jacob Dankert |
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| Affiliation: | Department of Medical Microbiology, Academic Medical Centre, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.;Department of Pulmonology, Academic Medical Centre, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands. |
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| Abstract: | 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 |
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