A Genome-Wide Helicobacter pylori Morphology Screen Uncovers a Membrane-Spanning Helical Cell Shape Complex

Author:

Yang Desirée C.1,Blair Kris M.12,Taylor Jennifer A.13,Petersen Timothy W.4,Sessler Tate1,Tull Christina M.1,Leverich Christina K.1,Collar Amanda L.1,Wyckoff Timna J.15,Biboy Jacob6,Vollmer Waldemar6,Salama Nina R.123ORCID

Affiliation:

1. Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

2. Molecular and Cellular Biology Ph.D. Program, University of Washington, Seattle, Washington, USA

3. Department of Microbiology, University of Washington School of Medicine, Seattle, Washington, USA

4. BD Biosciences, Seattle, Washington, USA

5. Division of Science and Mathematics, University of Minnesota, Morris, Minnesota, USA

6. Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, United Kingdom

Abstract

The stomach ulcer and cancer-causing pathogen Helicobacter pylori has a helical cell shape which facilitates stomach infection. Using light scattering to measure perturbations of cell morphology, we identified 28 genes that influence different aspects of cell shape. A mutant in a previously uncharacterized protein renamed Csd7 failed to form any helical cells. Biochemical analyses showed that Csd7 collaborates with other proteins to stabilize the cell wall-degrading enzyme Csd1. Csd7 also links Csd1 with a putative filament-forming protein via protein-protein interactions. These data suggest that helical cell shape arises from a highly orchestrated program to regulate cell wall modifications. Targeting of this helical cell shape-promoting program could offer new ways to block infectivity of this important human pathogen.

Funder

Wellcome Trust

HHS | NIH | National Cancer Institute

HHS | NIH | National Institute of Allergy and Infectious Diseases

National Science Foundation

American Cancer Society

Publisher

American Society for Microbiology

Subject

Molecular Biology,Microbiology

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