Dynamique de formation de coccoïdes de Helicobacter pylori et rôle dans la pathogénèse

Helicobacter pylori is a microaerophilic epsilon-proteobacterium known to cause peptic ulcers and gastric cancer and has infected more than 50% of the world's population. Until today, its route of transmission and all features implicated in its pathogenesis remain poorly understood. As its name implies, this organism possesses a helical shape that aids in its colonization of the stomach by allowing it to bore into the mucus layer in a corkscrew-like motion. Remarkably, H. pylori has been observed to live a dimorphic lifestyle and can transform into spherical coccoids made up of a distinctive peptidoglycan motif that evades immune recognition. This coccoid form has also been suggested to be its persistent form participating in antibiotic tolerance. We initially hypothesized that the helical-rod H. pylori would transition into a U-form before morphing into a spherical coccoid since observation of this intermediate had been reported by many studies. Using fluorescence imaging coupled with AI-assisted analysis, we tracked the structural changes inside the peptidoglycan of this organism during the transformation and observed that they transitioned directly from helical-rod into spherical coccoid and that the U-form was a subset population rather than an intermediate. Further investigations revealed the coccoid form of H. pylori to possess a thickened cell wall near the cellular poles and to be devoid of this structure in the spherical sac. They were also found to have intact lipid membranes with genetic contents. Meanwhile, the U-form was demonstrated to have its outer membrane detached from the PGN, lacked DNA, and emitted a unique autofluorescence signal. Altogether, these findings deepen our understanding of the coccoid form of H. pylori and suggest the existence of a novel subpopulation in this species.