28 May – Talk by Cynthia Sharma

Cynthia SharmaCynthia Sharma, University of Würzburg, Research Center for Infectious Diseases (ZINF), gives a talk titled “Regulatory RNAs in the pathogenic Epsilonproteobacteria, Helicobacter pylori and Campylobacter jejuni“.

Wednesday, 28/05/14 at 5 pm
Seminar room N100/0.15, Biocenter, Campus Riedberg

Helicobacter pylori, the causative agent of gastritis, ulcers, and gastric cancer, and Campylobacter jejuni, the most common cause of bacterial gastroenteritis to date, are two major human pathogens. Genome sequencing revealed their potential proteins and genetic diversity, but less is known about the transcriptional organization and post-transcriptional regulation of these Gram-negative Epsilonproteobacteria. Previously, Helicobacter pylori was even regarded as an organism without riboregulation since it lacks, like 50% of all bacteria, the RNA chaperone Hfq. However, based on a novel differential RNA-sequencing approach (dRNA-seq), we had recently defined a genome-wide map of transcriptional start sites (TSS) and identified more than 60 sRNAs in H. pylori strain 26695. We have now applied a comparative dRNA-seq approach to multiple strains of the emerging food-borne pathogen, Campylobacter jejuni, to understand how transcriptome differences could contribute to phenotypic differences among closely related strains. Our study revealed that the majority of TSS is conserved among strains, but we also observed strain-specific promoter usage and small RNA (sRNA) repertoires, which could contribute to strain-specific gene regulation.

Based on our transcriptome datasets, we are now using Helicobacter and Campylobacter as new model organisms for riboregulation in virulent bacteria and bacteria that lack Hfq. We have started with the functional characterization of abundant sRNAs as well as identification of associated RNA-binding proteins and new regulatory mechanisms. For example, we could show that a trans-acting sRNA, RepG, from Helicobacter directly base-pairs with a homopolymeric G-repeat in the mRNA leader of the TlpB chemotaxis receptor and that length variation of the G-repeat determines the outcome (activation or repression) of RepG-mediated post-transcriptional regulation. Overall, the identification and characterization of diverse sRNA candidates in Helicobacter and Campylobacter indicates that riboregulation constitutes an important layer of gene-expression control in these major human pathogens and will provide new insights into regulatory mechanisms and virulence control.