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.
Highlights
Helicobacter pylori is a helical rod shaped Gram(-) Proteobacterium with only one known niche, the viscous epithelial mucus layer of the human stomach [1]
We demonstrate straight rod mutants of H. pylori are attenuated in stomach colonization without apparent changes in proinflammatory activity
As csd4 mutants are the straightest of the two rodshaped mutants, we focused further characterization on this mutant to understand the impact of its dramatic cell shape change on stomach colonization
Summary
Helicobacter pylori is a helical rod shaped Gram(-) Proteobacterium with only one known niche, the viscous epithelial mucus layer of the human stomach [1]. Pathologic examination of gastric biopsy specimens reveals H. pylori dispersed within the gastric mucus layer and in direct contact with the gastric epithelial cells [3]. H. pylori’s helical cell shape may contribute to this process by enabling the bacteria to bore into the mucus layer via a cork-screwing mechanism [9]. Mathematical modeling has predicted helical shape improves propulsion efficiency in the form of speed in viscous polymer solutions [11]. H. pylori and Campylobacter jejuni have been shown to swim faster at higher viscosities than certain rod-shaped species (e.g. Escherichia coli) in solutions of methylcellulose [3,12]
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