title: Multiple peptidoglycan modification networks modulate Helicobacter pylori's cell shape, motility, and colonization potential.
abstract: Helical cell shape of the gastric pathogen Helicobacter pylori has been suggested to promote virulence through viscosity-dependent enhancement of swimming velocity. However, H. pylori csd1 mutants, which are curved but lack helical twist, show normal velocity in viscous polymer solutions and the reason for their deficiency in stomach colonization has remained unclear. Characterization of new rod shaped mutants identified Csd4, a DL-carboxypeptidase of peptidoglycan (PG) tripeptide monomers and Csd5, a putative scaffolding protein. Morphological and biochemical studies indicated Csd4 tripeptide cleavage and Csd1 crosslinking relaxation modify the PG sacculus through independent networks that coordinately generate helical shape. csd4 mutants show attenuation of stomach colonization, but no change in proinflammatory cytokine induction, despite four-fold higher levels of Nod1-agonist tripeptides in the PG sacculus. Motility analysis of similarly shaped mutants bearing distinct alterations in PG modifications revealed deficits associated with shape, but only in gel-like media and not viscous solutions. As gastric mucus displays viscoelastic gel-like properties, our results suggest enhanced penetration of the mucus barrier underlies the fitness advantage conferred by H. pylori's characteristic shape.
authors.affiliation: Molecular and Cellular Biology Graduate Program, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Laura K
authors.initials: LK
authors.lastname: Sycuro
authors.forename: Timna J
authors.initials: TJ
authors.lastname: Wyckoff
authors.forename: Jacob
authors.initials: J
authors.lastname: Biboy
authors.forename: Petra
authors.initials: P
authors.lastname: Born
authors.forename: Zachary
authors.initials: Z
authors.lastname: Pincus
authors.forename: Waldemar
authors.initials: W
authors.lastname: Vollmer
authors.forename: Nina R
authors.initials: NR
authors.lastname: Salama
mesh_terms: D000818:Animals; D018407:Bacterial Physiological Phenomena / Q000235:genetics; D001426:Bacterial Proteins / Q000378:metabolism*; D002473:Cell Wall / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism / Q000382:microbiology; D016481:Helicobacter Infections / Q000378:metabolism / Q000382:microbiology*; D016480:Helicobacter pylori / Q000166:cytology / Q000472:pathogenicity / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009068:Movement; D009093:Mucus / Q000378:metabolism / Q000382:microbiology; D009154:Mutation; D010457:Peptidoglycan / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D010457:Peptidoglycan