Prof Elizabeth Hartland and Dr Shivani Pasricha
In this study we observed that an uncharacterized Legionella protein, SnpL localizes to the cell nucleus during the infection of macrophages and binds to host protein SUPT5H. SUPT5H is integral to the regulated pausing and activation of gene transcription throughout the genome, particularly of highly expressed genes and genes involved in stimulus-response pathways.
Centre for Innate Immunity & Infectious Diseases
Innate Immune Responses to Infection
Journal and article title
We were amazed that a single Legionella protein has the potential to traffic all the way to the host nucleus without a known localisation signal, target a host protein with such strong specificity and elicit a huge global increase in host gene expression.
The activity of SnpL highlights the ability of L. pneumophila to control fundamental eukaryotic processes such as transcription and deepens our understanding of Legionella intracellular biology. It has led to the identification of cellular processes (i.e transcriptional elongation) that may be targeted to facilitate bacterial replication. The conservation of SnpL among all Legionella pneumophila strains and a wide range of Legionella species suggests its function assists survival of the bacteria in eukaryotic hosts and thus the persistence of Legionellae in the environment. With this knowledge we can now move forward with trying to identify other Legionella proteins that are targeting the host nucleus and elucidate preventative measures.