A new sugar for an old phage: A c-di-GMP dependent polysaccharide pathway sensitizes E. coli for bacteriophage infection

Sellner, Benjamin and Prakapaitė, Rūta and van Berkum, Margo and Heinemann, Matthias and Harms, Alexander and Jenal, Urs. (2021) A new sugar for an old phage: A c-di-GMP dependent polysaccharide pathway sensitizes E. coli for bacteriophage infection.

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Bacteriophages are ubiquitous parasites of bacteria and major drivers of bacterial ecology and evolution. Despite an ever-growing interest in their biotechnological and therapeutic applications, detailed knowledge of the molecular mechanisms underlying phage-host interactions remains scarce. Here, we show that bacteriophage N4 exploits a novel surface glycan, NGR, as a receptor to infect its host Escherichia coli . We demonstrate that this process is regulated by the second messenger c-di-GMP and that N4 infection is specifically stimulated by the diguanylate cyclase DgcJ while the phosphodiesterase PdeL effectively protects E. coli from N4-mediated killing. PdeL-mediated protection requires its catalytic activity to reduce c-di-GMP and includes a secondary role as a transcriptional repressor. We demonstrate that PdeL binds to and represses the promoter of the wec operon, which encodes components of the ECA exopolysaccharide pathway. However, only the acetylglucosamine epimerase WecB but none of the other ECA components is required for N4 infection. Based on this, we postulate that NGR is an N-acetylmannosamine-based carbohydrate polymer that is produced and exported to the cell surface of E. coli in a c-di-GMP dependent manner where it serves as a receptor for N4. This novel carbohydrate pathway is conserved in E. coli and other bacterial pathogens, serves as the primary receptor for a range of N4-like bacteriophages, and is induced at elevated temperature and by specific amino acid-based nutrients. These studies provide an entry point into understanding how bacteria use specific regulatory mechanisms to balance costs and benefits of highly conserved surface structures.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Infection Biology > Molecular Microbiology (Jenal)
05 Faculty of Science > Departement Biozentrum > Growth & Development > Molecular Microbiology (Jenal)
UniBasel Contributors:Jenal, Urs and Harms, Alexander and Prakapaité, Ruta and Sellner, Benjamin
Item Type:Working Paper
Publisher:Cold Spring Harbor Laboratory
Number of Pages:31
Note:Publication type according to Uni Basel Research Database: Discussion paper / Internet publication
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Last Modified:01 Dec 2021 13:54
Deposited On:01 Dec 2021 13:54

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