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J. Bacteriol., 05 1995, 2475-2480, Vol 177, No. 9
A van der Ende, CT Hopman, S Zaat, BB Essink, B Berkhout and J Dankert
The class 1 outer membrane protein encoded by the porA gene of Neisseria
meningitidis is a candidate for a vaccine against meningococcal infection.
The expression of class 1 outer membrane protein displays phase variation
between three expression levels. Northern (RNA) blot and primer extension
analysis revealed that this phase variation is regulated at the
transcriptional level. The start site for transcription is located 59 bp
upstream of the translational initiation codon. Sequence analysis of the
promoter region of the porA gene of a variant without class 1 protein
expression revealed nine contiguous guanidine residues between the -10 and
-35 domains. Comparison of promoter sequences of different phase variants
indicated that the length of the polyguanidine stretch correlated with the
expression level of the class 1 outer membrane protein; the presence of 11,
10, or 9 contiguous guanidine residues results in high levels, medium
levels, or no expression of class 1 mRNA, respectively. These results
suggest that the variable porA expression levels seen in different isolates
are modulated by guanidine residue insertion and/or deletion due to
slipped-strand mispairing on the polyguanidine stretch within the
intervening sequence of the -35 and -10 regions of the promoter. The phase
variation of class 1 outer membrane protein may provide a molecular
mechanism to evade the host immune defense. Therefore, the protective
efficacy of a vaccine based on class 1 outer membrane protein may be
questioned.
Copyright © 1995, American Society for Microbiology
Variable expression of class 1 outer membrane protein in Neisseria meningitidis is caused by variation in the spacing between the -10 and - 35 regions of the promoter
Department of Medical Microbiology, University of Amsterdam, The Netherlands.
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