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Modulation of Peptidoglycan Synthesis by Recycled Cell Wall Tetrapeptides

53 Pages Posted: 7 Jan 2020 Sneak Peek Status: Review Complete

See all articles by Sara B. Hernández

Sara B. Hernández

University of Umea - The Laboratory for Molecular Infection Medicine Sweden

Tobias Dörr

Cornell University - Weill Institute for Cell and Molecular Biology

Matthew K. Waldor

Harvard University - Department of Microbiology

Felipe Cava

University of Umea - The Laboratory for Molecular Infection Medicine Sweden

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Abstract

The bacterial cell wall is made of peptidoglycan (PG), a polymer that is essential for maintenance of cell shape and survival. During growth, bacteria remodel their PG, releasing fragments that are predominantly re-internalized and recycled. Here, we show that Vibrio cholerae recycles PG fragments modified with non-canonical D-amino acids (NCDAA), which lead to the accumulation of cytosolic PG tetrapeptides. We demonstrate that accumulation of recycled tetrapeptides has two regulatory consequences for the cell wall: reduction of D,D-cross-linkage and reduction of PG synthesis. We have demonstrated that L,D-carboxypeptidases from five different species show a preferential activity for substrates containing canonical (D-Alanine) vs. non-canonical (D-Methionine) D-amino acids, suggesting that accumulation of recycled tetrapeptides in NCDAA-rich environments is a widespread phenomenon. Collectively, this work highlights the role of NCDAA in interspecies PG modulation and reveals an unnoticed link between PG recycling and synthesis to promote optimal cell wall assembly and composition.

Keywords: cell wall, Vibrio cholerae, peptidoglycan recycling, L, D-carboxypeptidase, L, D-transpeptidase, NCDAA, D-amino acids, Tn-seq

Suggested Citation

Hernández, Sara B. and Dörr, Tobias and Waldor, Matthew K. and Cava, Felipe, Modulation of Peptidoglycan Synthesis by Recycled Cell Wall Tetrapeptides. Available at SSRN: https://ssrn.com/abstract=3513568 or http://dx.doi.org/10.2139/ssrn.3513568
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Sara B. Hernández

University of Umea - The Laboratory for Molecular Infection Medicine Sweden

Umeå, SE-901 87
Sweden

Tobias Dörr

Cornell University - Weill Institute for Cell and Molecular Biology

United States

Matthew K. Waldor

Harvard University - Department of Microbiology

United States

Felipe Cava (Contact Author)

University of Umea - The Laboratory for Molecular Infection Medicine Sweden ( email )

Umeå, SE-901 87
Sweden

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