Peptidoglycan Crosslinking Relaxation Promotes Helicobacter pylori's Helical Shape and Stomach Colonization

SummaryThe mechanisms by which bacterial cells generate helical cell shape and its functional role are poorly understood. Helical shape of the human pathogen Helicobacter pylori may facilitate penetration of the thick gastric mucus where it replicates. We identified four genes required for helical shape: three LytM peptidoglycan endopeptidase homologs (csd1–3) and a ccmA homolog. Surrounding the cytoplasmic membrane of most bacteria, the peptidoglycan (murein) sacculus is a meshwork of glycan strands joined by peptide crosslinks. Intact cells and isolated sacculi from mutants lacking any single csd gene or ccmA formed curved rods and showed increased peptidoglycan crosslinking. Quantitative morphological analyses of multiple-gene deletion mutants revealed each protein uniquely contributes to a shape-generating pathway. This pathway is required for robust colonization of the stomach in spite of normal directional motility. Our findings suggest that the coordinated action of multiple proteins relaxes peptidoglycan crosslinking, enabling helical cell curvature and twist.

Graphical AbstractFigure optionsDownload high-quality image (401 K)Download as PowerPoint slideHighlights
► Helical shape of H. pylori requires relaxation of cell wall peptide crosslinks
► Three peptidases and a scaffolding protein collaborate in generating helical shape
► Helical shape and/or peptidoglycan modification promotes stomach colonization
► Loss of helical twist minimally alters motility