The Mycoplasma Metalloproteome (MycoMet)

Presentation

Transition metals are required by all life forms to carry out central functions necessary for survival. Moreover, they are at the heart of the host-pathogen battle as the host immune system sequesters essential metals from pathogens. In order to acquire metals and maintain their metal homeostasis, microbial pathogens have developed vital mechanisms involving a range of proteins that constitute their metalloproteome. Bacteria of the Mycoplasma genus have amongst the smallest genomes known for an autonomously replicating cell. Through evolution, genomes of mycoplasmas underwent drastic reduction to select a minimal set of essential genes. As such, the metalloproteome of mycoplasmas might represent a minimal metalloproteome required to perform some of the most fundamental functions supporting life. Many mycoplasmas are pathogens of vertebrates that are alarming in the raise of antimicrobial resistance, e.g., the avian pathogen Mycoplasma gallisepticum and the human pathogen Mycoplasma pneumoniae causing respiratory diseases. An attractive way to design drugs against these pathogens is to target essential components of their metalloproteome. However, microbial metalloproteomes are largely uncharacterized, especially in mycoplasmas. The MycoMet team aims to decipher the mechanisms of metal acquisition and utilization in the minimalist mycoplasma organisms through a multidisciplinary approach combining biochemistry, structural biology, biophysics and bioinformatics. The project will unravel new biochemical mechanisms and answer fundamental questions regarding the metal homeostasis and metalloenzyme chemistry essential to minimal microbial pathogens. Ultimately, the project will identify key components in the survival of mycoplasmas, thereby uncovering putative new drug targets in order to combat antimicrobial resistance.

Project MIMESIS - Deciphering the Minimal Metalloproteome Essential to Mycoplasma Survival (ANR website)

Project Structural dynamics of oxidoreductases crucial for the survival of human pathogens (FBF website)

SLAC article Shining light on the radical production of DNA building blocks (SLAC website)

Publications

• Hugo Lebrette*, Vivek Srinivas, Juliane John, Oskar Aurelius, Rohit Kumar, Daniel Lundin, Aaron S Brewster, Asmit Bhowmick, Abhishek Sirohiwal, In-Sik Kim, Sheraz Gul, Cindy Pham, Kyle D Sutherlin, Philipp Simon, Agata Butryn, Pierre Aller, Allen M Orville, Franklin D Fuller, Roberto Alonso-Mori, Alexander Batyuk, Nicholas K Sauter, Vittal K Yachandra, Junko Yano, Ville R I Kaila, Britt-Marie Sjöberg, Jan Kern*, Katarina Roos, Martin Högbom*.
  Structure of a ribonucleotide reductase R2 protein radical
  Science
  2023 Oct *corresponding author
• Juliane John, Oskar Aurelius, Vivek Srinivas, Patricia Saura, In-Sik Kim, Asmit Bhowmick, Philipp S Simon, Medhanjali Dasgupta, Cindy Pham, Sheraz Gul, Kyle D Sutherlin, Pierre Aller, Agata Butryn, Allen M Orville, Mun Hon Cheah, Shigeki Owada, Kensuke Tono, Franklin D Fuller, Alexander Batyuk, Aaron S Brewster, Nicholas K Sauter, Vittal K Yachandra, Junko Yano, Ville RI Kaila, Jan Kern, Hugo Lebrette, Martin Högbom.
  Redox-controlled reorganization and flavin strain within the ribonucleotide reductase R2b–NrdI complex monitored by serial femtosecond crystallography
  eLife
  2022 Sep
• Rahul Banerjee, Vivek Srinivas, Hugo Lebrette.
  Ferritin-Like Proteins: A Conserved Core for a Myriad of Enzyme Complexes
  Subcellular Biochemistry
  2022 Sep
• Riccardo Diamanti, Vivek Srinivas, Annika I Johansson, Anders Nordström, Julia J Griese, Hugo Lebrette, Martin Högbom.
  Comparative structural analysis provides new insights into the function of R2-like ligand-binding oxidase
  FEBS Letters
  2022 Jun
• Alex Perálvarez-Marín, Eric Baranowski, Paula Bierge, Oscar Q Pich, Hugo Lebrette.
  Metal utilization in genome-reduced bacteria: Do human mycoplasmas rely on iron?
  Computational and Structural Biotechnology Journal
  2021 Oct

Funding