A Repetitive DNA Element Regulates Expression of the Sialic Acid Binding Adhesin by a Rheostat-like Mechanism

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During persistent H. pylori infection, the local gastric milieu is constantly altered by host responses and inflammation fluxes. As adhesion is crucial to maintain infection, appropriate adaptation of bacterial adherence properties is required to meet these environmental fluctuations. H. pylori uses the SabA protein to bind glycan receptors present on inflamed stomach mucosa. SabA expression can be turned on or off via known genetic mechanisms; however, how fine-tuning of SabA expression occurs to match changes in receptor levels is still unknown. The H. pylori genome encodes few trans-acting regulators but has numerous simple sequence repeats (SSR), i.e. hypermutable DNA segments. Here, we have deciphered a mechanism where a T-repeat tract, located in the sabA promoter region, affects SabA expression. The mechanism involves structural alterations of the promoter DNA that affects interaction of the RNA polymerase, without input from known trans-acting regulators. This mechanism is likely not unique for SabA or to H. pylori, but also applicable to other pathogens with high abundance of SSRs and limited set of transcription factors. Our findings contribute to understanding of the important bacterial-host interplay, and to mechanisms that generate heterogeneous populations of best-fit clones, i.e. stochastic switching.

Vyšlo v časopise: A Repetitive DNA Element Regulates Expression of the Sialic Acid Binding Adhesin by a Rheostat-like Mechanism. PLoS Pathog 10(7): e32767. doi:10.1371/journal.ppat.1004234
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004234

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