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Dr. Hugo Lebrette - Deciphering the essential metalloproteome from minimal genomes to combat antimicrobial resistance

Joint IPBS and CBI Seminar

Hugo Lebrette

Dept. of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden

Deciphering the essential metalloproteome from minimal genomes to combat antimicrobial resistance

Life is impossible without metals. Every organism requires metals to perform specific functions essential for their survival. Through evolution, genomes of certain organisms underwent drastic reduction to select a minimal set of essential genes. Metalloproteins from these organisms constitute an essential metalloproteome required to perform some of the most fundamental functions supporting life. Deciphering this metalloproteome would allow the design of novel strategies to target key components for the survival of a broad range of pathogenic microorganisms.
Mycoplasma species, including the human pathogens M. genitalium and M. pneumoniae, have amongst the smallest genomes known for an autonomously replicating cell. Although putatively essential, their metalloproteomes remain largely uncharacterized, and their metal requirements prove to be puzzling. Indeed, we reported recently the discovery of a ribonucleotide reductase in Mycoplasma pathogens which had evolved to overcome the requirement of Mn ions, possibly as an adaptation to metal starvation induced by the host immune system [1]. By implementing a multidisciplinary approach, including X-ray free electron laser [2,3] and microcrystal electron diffraction [4], I will discuss how the essential metalloproteome of Mycoplasma could be unveiled and help finding new ways to combat antimicrobial resistance.

Selected references

1. Srinivas V*, Lebrette H* et al. Metal-free ribonucleotide reduction powered by a DOPA radical in Mycoplasma pathogens. Nature 2018, 563(7731):416-420

2. Fuller FD, Gul S, Chatterjee R, Burgie ES, Young ID, Lebrette H et al. Drop-on-demand sample delivery for studying biocatalysts in action at X-ray free-electron lasers. Nat Methods 2017, 14(4):443-449

3. Srinivas V, Banerjee R, Lebrette H et al. High resolution XFEL structure of the soluble methane monooxygenase hydroxylase complex with its regulatory component at ambient temperature in two oxidation states. J Am Chem Soc 2020, Jul 20. doi: 10.1021/jacs.0c05613

4. Xu H*, Lebrette H* et al. Solving a new R2lox protein structure by micro-crystal electron diffraction. Sci Adv 2019, 5(8):eaax4621

 

Contacts: Olivier Neyrolles (olivier.neyrolles@ipbs.fr) & Fran├žois Cornet (francois.cornet@univ-tlse3.fr)

 

Note for visitors: Please come with a valid identity card

Due to the COVID-19-related situation, this seminar is restricted to IPBS and CBI members only.

 

Registration to attend the seminar on-line: click here

 

11 Sep

11:00 - 12:00

Fernand Gallais Conference room