Theme 1 Brucella virulence
Brucella is a facultative intracellular pathogen. It uses its virulence factors, including effectors translocated by the VirB type IV secretion system, to block host cell defences and create a novel intracellular niche which allows it to survive and replicate in host macrophages. In animals the bacterium causes infectious abortion and other reproductive problems while in man the disease is also known as Malta or undulant Fever. Brucellosis is an important zoonosis and the disease in man is very severe and is contracted following direct contact with infected animals or following the ingestion dairy products derived from infected animals. Brucellosis has a world-wide impact in terms of its epidemiology, human health risks and its impact on trade. The greatest impact of brucellosis is in the poorer, rural areas of the world, without the funds, nor the infrastructure to establish surveillance and eradication programs.
1. Role of T4SS in Brucella virulence
To understand how Brucella can cause disease in susceptible animals and humans we are using bacterial genetics and cellular microbiology techniques to identify and characterise the bacterial and host factors that play a role in the infection process. One of the major virulence factors is the VirB type IV secretion system that we identified (1). Our interests include understanding how the T4SS delivers effectors to host cells and characterisation of their effects on host cell biology.
2. Host factors required for infection
We have identified several host factors that are important for successful infection. One of these is the CD98hc protein (Keriel et al 2014). We are now investigating the role of CD98 in the infection of different cell types, including macrophages and trophoblasts.
3. Brucella genomics and evolution
Our group has a long history of the area of Brucella genomics and evolution. We are analysing the virulence of atypical and new Brucella isolates and using genomic data to map the evolution steps towards becoming a stealth pathogen.