Deciphering the architecture and function of bacterial membrane metal efflux platforms – BAC-MMEP
Metal ions are toxic in large quantities and their intracellular concentration must be finely regulated. We have previously found that metals are used by macrophages to poison the tuberculosis bacillus, Mycobacterium tuberculosis (Mtb), and that metal efflux pumps of the P-ATPase superfamily are required for Mtb to multiply within these cells. It is not known how metals are exported through the mycobacterial envelope. Our project aims to understand the interaction between Mtb P-ATPases and members of a new family of small intrinsically disordered proteins (IDPs) encoded in operon with these transporters. Based on our preliminary results, we propose that these IDPs act both as a new type of metallochaperones, capable of binding metals and donating them to efflux pumps, and as scaffold proteins for the supramolecular assembly of P-ATPase-containing microdomains in the plasma membrane, structures that we propose to call "metal efflux platforms".
This project will lead to a better understanding of the molecular mechanisms of metal resistance in Mtb, and possibly to the development of new anti-tuberculosis drugs. Similar IDP proteins are present in other pathogens, such as streptococci, so our results could have implications for other infectious diseases. Finally, a better understanding of metal transport in bacteria could have applications in the field of bio-remediation, particularly in the context of the clean-up of environments contaminated by heavy metals.
Project coordination
Olivier NEYROLLES (INSTITUT de PHARMACOLOGIE et de BIOLOGIE STRUCTURALE)
The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.
Partner
IPBS INSTITUT de PHARMACOLOGIE et de BIOLOGIE STRUCTURALE
IPBS INSTITUT de PHARMACOLOGIE et de BIOLOGIE STRUCTURALE
IPBS INSTITUT de PHARMACOLOGIE et de BIOLOGIE STRUCTURALE
IINS INSTITUT INTERDISCIPLINAIRE DE NEUROSCIENCES
Help of the ANR 673,469 euros
Beginning and duration of the scientific project:
September 2021
- 42 Months