Dr. Suzana P. Salcedo - Control of the subcellular localization of host nuclear proteins by Brucella effectors

Brucellosis is an important zoonotic disease caused by intracellular bacteria of the genus Brucella, and considered by the World Health Organisation to be one of the most widespread bacterial zoonosis worldwide.This pathogen ensures its survival and proliferation inside host cells by secreting effector proteins via a type IV secretion system. These effectors modulate various cellular functions including immune response and intracellular trafficking.

Bacterial targeting of the nucleus is a major virulence strategy shared by a number of plant and animal pathogens. In order to manipulate nuclear functions and eukaryotic gene expression, bacteria inject into host cells nuclear-targeting effector proteins, known as nucleomodulins. We have recently identified two such effectors from Brucella abortus. We have found that these two effectors interact with each other to modulate subcellular spatial dynamics of nuclear proteins during infection. Combining cell biology and structure-function studies we have identified their cellular targets and characterized the molecular interactions taking place. The consequences of these interactions will be further discussed in the context of Brucella pathogenesis.

Selected publications

• Coronas-Serna JM, Louche A, Rodríguez-Escudero M, Roussin M, Imbert PRC, Rodríguez-Escudero I, Molina M, Gorvel JP, Cid VJ*, Salcedo SP* (2020) The TIR-domain containing effectors BtpA and BtpB from Brucella abortus block energy metabolism. PLoS Pathogens 16(4):e1007979
• Roussin M and Salcedo SP (2021) NAD+-targeting by bacteria: an emerging weapon in pathogenesis. FEMS Microbiol Rev fuab037
• Luizet JB, Raymond J, Lacerda TLS, Barbieux E, Kambarev S, Bonici M, Lembo F, Willemart K, Borg JP, Celli J, Gérard FCA, Muraille E, Gorvel JP and Salcedo SP (2021) The Brucella effector BspL targets the ER-associated degradation (ERAD) pathway and delays bacterial egress from infected cells. Proc Natl Acad Sci USA 118(32):e2105324118
• PREPRINT: Louche A, Blanco A, Lacerda TLS, Lionnet C, Bergé C, Rolando M, Lembo F, Borg4JP, Buchrieser C, Nagahama M, Gorvel JP, Gueguen-Chaignon V, Terradot L, Salcedo SP (2021) The unique Brucella effectors NyxA and NyxB target SENP3 to modulate the subcellular localisation of nucleolar proteins. bioRxiv https://doi.org/10.1101/2021.04.23.441069