Variation in expression of the Haemophilus influenzae HMW adhesins: a prokaryotic system reminiscent of eukaryotes

Expression of a number of eukaryotic genes is regulated by long stretches of tandem repeats located within the 5' untranslated region of the particular gene. In this study, we describe a regulatory system in Haemophilus influenzae with striking similarities to those found in eukaryotes. We show that expression of the HMW1 and HMW2 adhesins varies based on the number of 7-bp tandem repeats in the hmw1A and hmw2A promoters. The repeats lie between two separate transcription initiation sites and exert a repressive effect, such that increases in repeat number result in step-wise decreases in levels of specific mRNA and protein production and vice versa. The range of expression of HMW1 and HMW2 varies between very weak and very strong, with a series of gradations in between. Variation in the number of repeats in the hmw1A and hmw2A promoters occurs in individual colonies passaged in vitro, in an animal model of infection, and during natural infection in humans. This system of regulation is unique in prokaryotes and likely enhances the pathogenicity of the organism by increasing adaptive potential.