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

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Abstract
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.