Legionella manipulates major host gene expression machinery during infection

Lead researcher

Prof Elizabeth Hartland and Dr Shivani Pasricha

Main finding

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

Centre for Innate Immunity & Infectious Diseases

Research group

Innate Immune Responses to Infection

Co-authors

Dr Ralf Schuelein
Mr Hugh Spencer
Dr Laura Dagley
Mr Peng Fei Li
Dr Lin Luo
Prof Jennifer Stow
Miss Gilu Abraham
Dr Thomas Naderer
Dr. Laura Gomez-Valero
Prof. Carmen Buchrieser
Prof. Chihiro Sugimoto
Assoc Prof. Junya Yamagishi
Dr. Andrew Webb
Dr. Shivani Pasricha
Prof. Elizabeth Hartland

Journal and article title

Most surprising

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.

Future implications

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.

Disease/health impact

Legionnaires Disease

Professor Elizabeth Hartland , Director and CEO of Hudson Institute of Medical Research