Long-term growth of Helicobacter pylori and its effects on adherence properties and expression of the sialic acid binding adhesin SabA

Helicobacter pylori infection causes a chronic gastric inflammation that may develop into peptic ulcer disease or gastric cancer. In order to cause a lifelong persistent infection, the bacterium has to cope with various changes that occur within the host during the infection. Diverse bacterial populations are found varying in the expression of their virulence genes and the phenomenon of phase variability via slipped strand mispairing (SSM) has been described for more than 40 genes in H. pylori. One example of such a gene that is frequently switched on and off is sabA that encodes for the sialic acid binding adhesin SabA. The SabA adhesin mediates adherence to inflamed gastric mucosa via its interaction to sialyl Lewis x (sLex) antigens. Sialylated structures such as sLex on epithelia are typically up-regulated in expression as a response to inflammation. The sabA gene carries two hotspots for SSM, a homopolymeric thymine (poly-T) tract upstream the translational start and a dinucleotide cytosine-thymine (CT repeat) tract in the 5’end of the coding region. The latter has previously been shown to be subjected to phase variation via strand slippages.This project reports on H. pylori populations with differential expression levels and adherence properties of the SabA adhesin after long-term culturing in different physiological conditions in terms of sialic acid availability. Moreover, subclones isolated from different time points and conditions were shown to have individual sLex-binding characteristics due to variations found within the poly-T/CT tracts, respectively. Phase shift off clones among the On-population were identified.