RESEARCH ARTICLE Coiled Coil Rich Proteins (Ccrp) Influence Molecular Pathogenicity of Helicobacter pylori

Pathogenicity of the human pathogen Helicobacter pylori relies on its capacity to adapt to a hostile environment and to escape the host response. Although there have been great ad-vances in our understanding of the bacterial cytoskeleton, major gaps remain in our knowl-edge of its contribution to virulence. In this study we have explored the influence of coiled coil rich proteins (Ccrp) cytoskeletal elements on pathogenicity factors of H. pylori. Deletion of any of the ccrp resulted in a strongly decreased activity of the main pathogenicity factor urease. We further investigated their role using in vitro co-culture experiments with the human gastric adenocarcinoma cell line AGS modeling H. pylori- host cell interactions. In-triguingly, host cell showed only a weak “scattering/hummingbird ” phenotype, in which host cells are transformed from a uniform polygonal shape into a severely elongated state char-acterized by the formation of needle-like projections, after co-incubation with any ccrp dele-tion mutant. Furthermore, co-incubation with the ccrp59mutant resulted in reduced type IV secretion system associated activities, e.g. IL-8 production and CagA translocation/phos-phorylation. Thus, in addition to their role in maintaining the helical cell shape of H. pylori Ccrp proteins influence many cellular processes and are thereby crucial for the virulence of this human pathogen