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A Superfamily of T6SS Antibacterial Effectors Displaying L,D-Carboxypeptidase Activity Towards Peptidoglycan

32 Pages Posted: 3 Mar 2020 Sneak Peek Status: Review Complete

See all articles by Stephanie Sibinelli-Sousa

Stephanie Sibinelli-Sousa

University of São Paulo (USP) - Departamento de Microbiologia

Julia Takuno Hespanhol

University of São Paulo (USP) - Departamento de Microbiologia

Gianlucca Gonçalves Nicastro

University of São Paulo (USP) - Departamento de Microbiologia

Bruno Yasui Matsuyama

University of São Paulo (USP) - Departamento de Bioquímica

Stephane Mesnage

University of Sheffield - Department of Molecular Biology and Biotechnology

Ankur Patel

University of Sheffield - Department of Molecular Biology and Biotechnology

Robson Francisco de Souza

University of São Paulo (USP) - Departamento de Microbiologia

Cristiane Rodrigues Guzzo

University of São Paulo (USP) - Departamento de Microbiologia

Ethel Bayer Santos

University of São Paulo (USP) - Departamento de Microbiologia

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Abstract

Type VI secretion systems (T6SSs) are contractile nanomachines used by bacteria to inject toxic effectors into competitors. The identity and mechanism of many effectors remain unknown. We characterized a Salmonella SPI-6 T6SS antibacterial effector called Tae5STM (type VI amidase effector 5). Tae5STM is toxic in target-cell periplasm and is neutralized by its cognate immunity protein (Tai5STM). Microscopy analysis revealed that cells expressing the effector stop dividing and lose cell envelope integrity. Bioinformatic analysis uncovered similarities between Tae5STM and the catalytic domain of L,D-transpeptidase. Point mutations on conserved catalytic histidine and cysteine residues abrogated toxicity. Biochemical assays revealed that Tae5STM displays L,D-carboxypeptidase activity, cleaving peptidoglycan tetrapeptides between meso-diaminopimelic acid3 and D-alanine4. Phylogenetic analysis showed that Tae5STM homologs constitutes a new superfamily of T6SS-associated amidase effectors distributed among α-, β- and γ-proteobacteria. This work expands our current knowledge about bacterial effectors used in interbacterial competition.

Keywords: Salmonella, T6SS, SPI-6, Tae5, effector, toxin, peptidoglycan, L, D-carboxypeptidase

Suggested Citation

Sibinelli-Sousa, Stephanie and Hespanhol, Julia Takuno and Nicastro, Gianlucca Gonçalves and Matsuyama, Bruno Yasui and Mesnage, Stephane and Patel, Ankur and de Souza, Robson Francisco and Guzzo, Cristiane Rodrigues and Bayer Santos, Ethel, A Superfamily of T6SS Antibacterial Effectors Displaying L,D-Carboxypeptidase Activity Towards Peptidoglycan. Available at SSRN: https://ssrn.com/abstract=3545509 or http://dx.doi.org/10.2139/ssrn.3545509
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Stephanie Sibinelli-Sousa

University of São Paulo (USP) - Departamento de Microbiologia ( email )

Brazil

Julia Takuno Hespanhol

University of São Paulo (USP) - Departamento de Microbiologia ( email )

Brazil

Gianlucca Gonçalves Nicastro

University of São Paulo (USP) - Departamento de Microbiologia ( email )

Brazil

Bruno Yasui Matsuyama

University of São Paulo (USP) - Departamento de Bioquímica ( email )

Brazil

Stephane Mesnage

University of Sheffield - Department of Molecular Biology and Biotechnology

United Kingdom

Ankur Patel

University of Sheffield - Department of Molecular Biology and Biotechnology

United Kingdom

Robson Francisco De Souza

University of São Paulo (USP) - Departamento de Microbiologia ( email )

Brazil

Cristiane Rodrigues Guzzo

University of São Paulo (USP) - Departamento de Microbiologia ( email )

Brazil

Ethel Bayer Santos (Contact Author)

University of São Paulo (USP) - Departamento de Microbiologia ( email )

Brazil

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