Identification and characterization of Brucella effector proteins

PhD ceremony: Mr. M.F. de Jong, 16.15 uur, Aula Academiegebouw, Broerstraat 5, Groningen

Dissertation: Identification and characterization of Brucella effector proteins

Promotor(s): prof. J.M. van Dijl

Faculty: Medical Sciences

Brucellosis is a global disease of domestic and wild mammals that is caused by intracellular bacteria of the genus Brucella. Brucella species have evolved to avoid the host’s immune system and infection is usually characterized by long-term persistence of the bacteria. One important Brucella virulence factor for intracellular survival and persistence in the host is the type IV secretion system (T4SS). At the start of the work presented in this thesis it was hypothesized that Brucella would use its T4SS to translocate effector proteins into host cells, since other important bacterial pathogens of humans, such as Helicobacter pylori and Legionella pneumophila, were found to use similar systems for this purpose. The goal of this research was the identification and characterization Brucella effector proteins. This would allow us to study the host cell pathways that are manipulated by Brucella during infection in more detail. This thesis describes the identification of three Brucella proteins (VceA, VceB and VceC), that are translocated into host macrophages by the Brucella T4SS. Both VceB and VceC are targeted to the endoplasmic reticulum (ER) of cells. Further experiments identified host proteins interacting with VceB and VceC, which suggests that both these effectors could be involved in manipulation of the host immune response. In conclusion, the present studies have provided novel insights into the virulence and survival strategies of Brucella, which are needed for the development of novel therapeutic interventions.