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Institut de Biologie StructuraleGrenoble / France

Contact person(s) related to this article / ZAPUN André

Presentation

The group’s research is focused on processes that involve the cell envelope of Streptococcus pneumoniae (the pneumococcus), such as cell wall metabolism, morphogenesis, or resistance to beta-lactams. We are also interested in morphogenesis events during sporulation of Bacillus subtilis and Clostridia.

Group leader : Thierry Vernet
Group members : Laure Bellard, Claire Durmort, Bowen Liu, Cécile Morlot, Jennyfer Trouvé, Anne-Marie Villard, André Zapun.

Overview

The pneumococcus is an ovoid Gram-positive commensal bacterium of the naso-pharyngeal flora of about 10% of the human population. When the pneumococcus invades other sites and tissues, it causes a variety of infectious diseases such as otitis, pneumonia, bacteremia and meningitis, killing over 1 million people per year worldwide.

Streptococcus pneumoniae

The cell wall of the pneumococcus is constituted mostly of peptidoglycan, teichoic acids and proteins. The peptidoglycan is a mesh-polymer constituted of chains of disaccharide cross-linked by short peptides. The peptidoglycan is essential as it confers mechanical resistance and shape to bacteria. Teichoic acids are complex linear polysaccharides attached to the membrane or the peptidoglycan. Teichoic acids play important roles in the interactions with the environment and the regulation of cell wall metabolism.

To tackle fundamental questions pertaining to the cell surface biology of S. pneumoniae, the Pneumococcus Group applies a wide range of techniques with a strong focus on biochemistry, structural biology and advanced optical microscopy.

Research topics

Cell wall metabolism, morphogenesis, and resistance to beta-lactams in the pneumococcus

Sporulation in B. subtilis and Clostridia

Keywords

Bacillus subtilis, bacterial cell wall, bacterial division, bacterial morphogenis, beta-lactams, Clostridia, murein, penicillin-binding proteins (PBPs), peptidoglycan, peptidoglycan hydrolases, pneumococcus, sporulation, Streptococcus pneumoniae, teichoic acids.

Techniques

  • Biochemistry
  • Crystallography
  • Detergent screening for membrane protein solubilzation (RoBioMol)
  • Fluorescence microscopy
  • High throughput cloning (RoBioMol)
  • High throughput site directed mutagenesis (RoBioMol)
  • Molecular biology
  • Pneumococcus genetics
  • Protein crystallization
  • Protein engineering
  • Quantitative PCR
  • Soluble and membrane protein biochemistry
  • Super-resolution microscopy PALM and dSTORM
  • Thermal Shift Assay (RoBioMol)

Recent publications

Trouve J, Mohamed A, Leisico F, Contreras-Martel C, Liu B, Mas C, et al. 2018 Structural characterization of the sporulation protein GerM from Bacillus subtilis. J Struct Biol In press.

Orelle C, Durmort C, Mathieu K, Duchêne B, Aros S, Fenaille F, et al. 2018 A multidrug ABC transporter with a taste for GTP. Sci Rep 8:2309.

Morlot C, Straume D, Peters K, Hegnar OA, Simon N, Villard A-M, et al. 2018 Structure of the essential peptidoglycan amidotransferase MurT/GatD complex from Streptococcus pneumoniae. Nat Commun 9:3180.

Morlot C, Rodrigues CDA. 2018 The New Kid on the Block: A Specialized Secretion System during Bacterial Sporulation. Trends Microbiol 26:663‑76.

Jacq M, Arthaud C, Manuse S, Mercy C, Bellard L, Peters K, et al. 2018 The cell wall hydrolase Pmp23 is important for assembly and stability of the division ring in Streptococcus pneumoniae. Sci Rep 8:7591.

Bonnet J, Wong Y-S, Vernet T, Di Guilmi AM, Zapun A, Durmort C. 2018 One-Pot Two-Step Metabolic Labeling of Teichoic Acids and Direct Labeling of Peptidoglycan Reveals Tight Coordination of Both Polymers Inserted into Pneumococcus Cell Wall. ACS Chem Biol 13:2010‑5.

Becke TD, Ness S, Gürster R, Schilling AF, di Guilmi A-M, Sudhop S, et al. 2018 Single Molecule Force Spectroscopy Reveals Two-Domain Binding Mode of Pilus-1 Tip Protein RrgA of Streptococcus pneumoniae to Fibronectin. ACS Nano 12:549‑58.

Di Guilmi AM, Bonnet J, Peiβert S, Durmort C, Gallet B, Vernet T, et al. 2017 Specific and spatial labeling of choline-containing teichoic acids in Streptococcus pneumoniae by click chemistry. Chem Commun 53:10572‑5.

Calvez P, Breukink E, Roper DI, Dib M, Contreras-Martel C, Zapun A. 2017 Substitutions in PBP2b from β-Lactam-resistant Streptococcus pneumoniae Have Different Effects on Enzymatic Activity and Drug Reactivity J Biol Chem. 292:2854‑65.

Bonnet J, Durmort C, Jacq M, Mortier-Barrière I, Campo N, VanNieuwenhze MS, et al. 2017 Peptidoglycan O-acetylation is functionally related to cell wall biosynthesis and cell division in Streptococcus pneumoniae. Mol Microbiol 106:832‑46.

Bonnet J, Cartannaz J, Tourcier G, Contreras-Martel C, Kleman JP, Morlot C, et al. 2017 Autocatalytic association of proteins by covalent bond formation: a Bio Molecular Welding toolbox derived from a bacterial adhesin. Sci Rep 7:43564.

Rodrigues CDA, Henry X, Neumann E, Kurauskas V, Bellard L, Fichou Y, et al. 2016 A ring-shaped conduit connects the mother cell and forespore during sporulation in Bacillus subtilis. Proc Natl Acad Sci USA 113:11585‑90.

Zapun A, Morlot C, Taha M-K. 2016 Resistance to β-Lactams in Neisseria ssp Due to Chromosomally Encoded Penicillin-Binding Proteins. Antibiotics 5:35.

Menezes MC, Imbert L, Kitano ES, Vernet T, Serrano SMT. 2016 Recombinant expression of the precursor of the hemorrhagic metalloproteinase HF3 and its non-catalytic domains using a cell-free synthesis system. Amino Acids 48:2205‑14.

Maréchal M, Amoroso A, Morlot C, Vernet T, Coyette J, Joris B. 2016 Enterococcus hirae LcpA (Psr), a new peptidoglycan-binding protein localized at the division site. BMC Microbiol 16:239.

Jacq M, Adam V, Bourgeois D, Moriscot C, Guilmi A-MD, Vernet T, et al. 2015 Remodeling of the Z-Ring Nanostructure during the Streptococcus pneumoniae Cell Cycle Revealed by Photoactivated Localization Microscopy. mBio 6:e01108-15.

A complete list of publications can be found here.