Peptidoglycan crosslinking relaxation promotes helicobacter pylori's helical shape and stomach colonization

Laura K. Sycuro; Zachary Pincus; Kimberley D. Gutierrez; Jacob Biboy; Chelsea A. Stern; Waldemar Vollmer; Nina R. Salama

doi:10.1016/j.cell.2010.03.046

Peptidoglycan crosslinking relaxation promotes helicobacter pylori's helical shape and stomach colonization

Laura K. Sycuro, Zachary Pincus, Kimberley D. Gutierrez, Jacob Biboy, Chelsea A. Stern, Waldemar Vollmer, Nina R. Salama

Research output: Contribution to journal › Article › peer-review

200 Scopus citations

Abstract

The 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.

Original language	English
Pages (from-to)	822-833
Number of pages	12
Journal	Cell
Volume	141
Issue number	5
DOIs	https://doi.org/10.1016/j.cell.2010.03.046
State	Published - May 2010

Keywords

Devbio
Humdisease
Microbio

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10.1016/j.cell.2010.03.046

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title = "Peptidoglycan crosslinking relaxation promotes helicobacter pylori's helical shape and stomach colonization",

abstract = "The 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.",

keywords = "Devbio, Humdisease, Microbio",

author = "Sycuro, {Laura K.} and Zachary Pincus and Gutierrez, {Kimberley D.} and Jacob Biboy and Stern, {Chelsea A.} and Waldemar Vollmer and Salama, {Nina R.}",

note = "Funding Information: This work was supported by NIH grants AI054423 and AI082026 (N.R.S.), a National Science Foundation Graduate Research Fellowship (L.K.S.), and grants from the Biotechnology and Biological Sciences Research Council (grant No. BB/F001231/1) and the European Commission (EUR-INTAFAR project) (W.V.). The contents are solely the responsibility of the authors and do not necessarily represent the official views of these funding agencies. We thank J. Fero, C. Tung, G. Cromie, S. Talarico, B. Stoddard, and D. Vollmer for technical assistance and consultation, P. Born for peptidoglycan analysis, R. Burmeister for graphic design, E. Gaynor and S. Miller for strains, and B. Schneider and staff (FHCRC Electron Microscopy Shared Resource), as well as V. Thompson and T. Davies (Newcastle University Electron Microscopy Research Service), for assistance with TEM. ",

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AU - Sycuro, Laura K.

AU - Pincus, Zachary

AU - Gutierrez, Kimberley D.

AU - Biboy, Jacob

AU - Stern, Chelsea A.

AU - Vollmer, Waldemar

AU - Salama, Nina R.

N1 - Funding Information: This work was supported by NIH grants AI054423 and AI082026 (N.R.S.), a National Science Foundation Graduate Research Fellowship (L.K.S.), and grants from the Biotechnology and Biological Sciences Research Council (grant No. BB/F001231/1) and the European Commission (EUR-INTAFAR project) (W.V.). The contents are solely the responsibility of the authors and do not necessarily represent the official views of these funding agencies. We thank J. Fero, C. Tung, G. Cromie, S. Talarico, B. Stoddard, and D. Vollmer for technical assistance and consultation, P. Born for peptidoglycan analysis, R. Burmeister for graphic design, E. Gaynor and S. Miller for strains, and B. Schneider and staff (FHCRC Electron Microscopy Shared Resource), as well as V. Thompson and T. Davies (Newcastle University Electron Microscopy Research Service), for assistance with TEM.

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N2 - The 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.

AB - The 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.

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Peptidoglycan crosslinking relaxation promotes helicobacter pylori's helical shape and stomach colonization

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