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Institut de Biologie StructuraleGrenoble / France

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Molecular interactions with the bacterial cell wall

Antibiotic resistance

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Jean-Pierre Simorre (CNRS researcher)
Catherine Bougault (MdC)
Pierre Gans (CEA Researcher)
Isabel Ayala (CNRS Engineer)
Laguri Cédric (CNRS Researcher)
Tomas Hosek (Post-Doc)
Roberto Maya Martinez (Post-Doc)


Molecular interactions with the bacterial cell wall by liquid state, standard and DNP solid state NMR

The bacterial cell wall is essential for the survival of bacteria. It gives the bacterial cell its shape and protects it against osmotic pressure, while allowing cell growth and division. It is made up of peptidoglycan (PG), a biopolymer forming a multi-gigadalton bag-like structure, and additionally in Gram-positive bacteria, of covalently linked anionic polymers called wall teichoic acids (WTA). TAs are thought to play important roles in ion trafficking, host-cell adhesion, inflammation and immune activation.

inhibition of the peptidoglycan enzymes by antibiotics

The machinery involved in the synthesis of this envelop is crucial and is one of the main antibiotic target. Different protein as transpeptidase, transpeptidase activator or hydrolase are recruited to maintain the morphogenesis of the peptidoglycan during the bacterial cell cycle. Based on few examples involved in the machinery of synthesis of the peptidoglycan, we will demonstrates that a combination of liquid and solid-state NMR can be a powerful tool to screen for cell-wall interacting proteins in vitro and on cell..
In particular, structure of the L,D-transpeptidases that results in b-lactam resistance in M. tuberculosis, has been studied in presence of the bacterial cell wall and in presence of antibiotic. The NMR study reveals new insights into the inhibition mechanism. [1]

On cell NMR by Solid state NMR

In parallel, we have investigated the potential of Dynamic Nuclear Polarization (DNP) to investigate cell surface directly in intact cells. Our results show that increase in sensitivity can be obtained together with the possibility of enhancing specifically cell-wall signals. It opens new avenues for the use of DNP-enhanced solid-state NMR as an on-cell investigation tool. [2]


Notes

[1] Dynamics induced by β-lactam antibiotics in the active site of Bacillus subtilis L,D-transpeptidase.
Lecoq L et al. Structure. 2012 May 9 ;20(5):850-61

[2] Solid-State NMR on Bacterial Cells : Selective Cell Wall Signal Enhancement and Resolution Improvement using Dynamic Nuclear Polarization.
Takahashi et al. J Am Chem Soc. 2013