Abstract
AbstractHelicobacter pyloriresistance to antibiotics is a growing problem and it increasingly leads to treatment failure. While the bacterium is present worldwide, the severity of the clinical outcomes is highly dependent on the geographical origin and genetic characteristics of the strains. One of the major virulence factors identified inH. pyloriis thecagpathogenicity island (cagPAI), which encodes a type IV secretion used to translocate effectors into human cells. Here, we investigated the genetic variability of thecagPAI among 13 antibiotic-resistantH. pyloristrains that were isolated from patient biopsies in Québec. Seven of the clinical strains carried thecagPAI, but only four could be readily cultivated under laboratory conditions. We observed variability of the sequences of CagA and CagL proteins that are encoded by thecagPAI. All clinical isolates induce interleukin-8 secretion and morphological changes upon co-incubation with epithelial gastric cancer cells and two of them produce extracellular T4SS pili. Finally, we demonstrate that molecule 1G2, a small molecule inhibitor of the Cagα protein from the model strainH. pylori26695, reduces interleukin-8 secretion in one of the clinical isolates. Co-incubation with 1G2 also inhibits the assembly of T4SS pili, suggesting a mechanism for its action on T4SS function.
Publisher
Cold Spring Harbor Laboratory